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Mowery, Yvonne Marie

Positions:

Assistant Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2012

M.D. — Duke University

Ph.D. 2012

Ph.D. — Duke University

Intern, Medicine

Duke University School of Medicine

Resident, Radiation Oncology

Duke University School of Medicine

Grants:

The Duke Preclinical Research Resources for Quantitative Imaging Biomarkers

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2017
End Date
August 31, 2022

Pembroluzimab and Radiation Therapy to Improve Outcome in Localized High-Risk Sarcoma

Administered By
Radiation Oncology
AwardedBy
Association of American Cancer Institutes
Role
Investigator
Start Date
May 01, 2017
End Date
February 29, 2020

Dissecting the Interplay between Tumor Mutational Load and the Immune System in Response of Primary Sarcomas to Radiation Therapy

Administered By
Radiation Oncology
AwardedBy
Conquer Cancer Foundation
Role
Principal Investigator
Start Date
July 01, 2017
End Date
June 30, 2018

Mechanisms that Regulate Sarcoma Response to Immune Checkpoint Inhibition of PD-1

Administered By
Radiation Oncology
AwardedBy
Sarcoma Alliance for Research Through Collaboration
Role
Investigator
Start Date
April 01, 2015
End Date
August 31, 2017

Mechanisms that Regulate Sarcoma Response to Immune Checkpoint Inhibition of PD-1

Administered By
Radiation Oncology
AwardedBy
Sarcoma Alliance for Research Through Collaboration
Role
Investigator
Start Date
April 01, 2015
End Date
August 31, 2017
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Awards:

Conquer Cancer Foundation of ASCO Young Investigator Award. Conquer Cancer Foundation of American Society of Clinical Oncology (ASCO).

Type
National
Awarded By
Conquer Cancer Foundation of American Society of Clinical Oncology (ASCO)
Date
January 01, 2017

Publications:

Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma.

Genetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, but how these tumours compare to tumours generated by conventional recombinase technology remains to be fully explored. Here we use CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar histology, growth kinetics, copy number variation and mutational load as assessed by whole exome sequencing. These results show that sarcomas generated with CRISPR-Cas9 technology are similar to sarcomas generated with conventional modelling techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate genotypically and phenotypically similar cancers.

Authors
Huang, J; Chen, M; Whitley, MJ; Kuo, H-C; Xu, ES; Walens, A; Mowery, YM; Van Mater, D; Eward, WC; Cardona, DM; Luo, L; Ma, Y; Lopez, OM; Nelson, CE; Robinson-Hamm, JN; Reddy, A; Dave, SS; Gersbach, CA; Dodd, RD; Kirsch, DG
MLA Citation
Huang, J, Chen, M, Whitley, MJ, Kuo, H-C, Xu, ES, Walens, A, Mowery, YM, Van Mater, D, Eward, WC, Cardona, DM, Luo, L, Ma, Y, Lopez, OM, Nelson, CE, Robinson-Hamm, JN, Reddy, A, Dave, SS, Gersbach, CA, Dodd, RD, and Kirsch, DG. "Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma." Nature communications 8 (July 10, 2017): 15999-.
PMID
28691711
Source
epmc
Published In
Nature Communications
Volume
8
Publish Date
2017
Start Page
15999
DOI
10.1038/ncomms15999

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer.The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice.Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT.US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434-1441. © 2016 American Cancer Society.

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, BG; Hopkins, MB; Palta, M
MLA Citation
Mowery, YM, Salama, JK, Zafar, SY, Moore, HG, Willett, CG, Czito, BG, Hopkins, MB, and Palta, M. "Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States." Cancer 123.8 (April 2017): 1434-1441.
PMID
27984651
Source
epmc
Published In
Cancer
Volume
123
Issue
8
Publish Date
2017
Start Page
1434
End Page
1441
DOI
10.1002/cncr.30461

(18)F-FDG PET/CT Response at 20 Gy Predicts Treatment Outcome for Head and Neck Squamous Cell Carcinoma (HNSCC).

Authors
Mowery, YM; Vergalasova, I; Yoo, DS; Limon, D; Das, SK; Hara, WY; Brizel, DM
MLA Citation
Mowery, YM, Vergalasova, I, Yoo, DS, Limon, D, Das, SK, Hara, WY, and Brizel, DM. "(18)F-FDG PET/CT Response at 20 Gy Predicts Treatment Outcome for Head and Neck Squamous Cell Carcinoma (HNSCC)." International journal of radiation oncology, biology, physics 96.2S (October 2016): E378-.
PMID
27674528
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E378
DOI
10.1016/j.ijrobp.2016.06.1582

Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States.

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, B; Hopkins, MB; Palta, M
MLA Citation
Mowery, YM, Salama, JK, Zafar, SY, Moore, HG, Willett, CG, Czito, B, Hopkins, MB, and Palta, M. "Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States." International journal of radiation oncology, biology, physics 96.2S (October 2016): S203-.
PMID
27675787
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
S203
DOI
10.1016/j.ijrobp.2016.06.505

Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series.

Authors
Olson, AC; Patel, K; Mowery, YM; Wynne, J; Ready, N; Kirkpatrick, JP; Salama, AK; Khan, MK
MLA Citation
Olson, AC, Patel, K, Mowery, YM, Wynne, J, Ready, N, Kirkpatrick, JP, Salama, AK, and Khan, MK. "Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series." International journal of radiation oncology, biology, physics 96.2S (October 2016): E97-E98.
PMID
27675516
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E97
End Page
E98
DOI
10.1016/j.ijrobp.2016.06.837

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis.

Authors
Kent, CL; Mowery, YM; Wright, AO; Kim, GJ; Desjardins, A; Peters, KB; Vlahovic, G; Friedman, HS; Cummings, TJ; McLendon, RE; Friedman, AH; Sampson, JH; Kirkpatrick, JP
MLA Citation
Kent, CL, Mowery, YM, Wright, AO, Kim, GJ, Desjardins, A, Peters, KB, Vlahovic, G, Friedman, HS, Cummings, TJ, McLendon, RE, Friedman, AH, Sampson, JH, and Kirkpatrick, JP. "Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis." International journal of radiation oncology, biology, physics 96.2S (October 2016): E83-E84.
PMID
27675478
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E83
End Page
E84
DOI
10.1016/j.ijrobp.2016.06.802

Immune Checkpoint Inhibition and Radiation Therapy in 2 Primary Mouse Models of Soft Tissue Sarcoma: Impact of Tumor Mutational Load.

Authors
Kent, CL; Mowery, YM; Wisdom, AJ; Van Mater, D; Castle, KD; Reddy, A; Dave, SS; Kirsch, DG
MLA Citation
Kent, CL, Mowery, YM, Wisdom, AJ, Van Mater, D, Castle, KD, Reddy, A, Dave, SS, and Kirsch, DG. "Immune Checkpoint Inhibition and Radiation Therapy in 2 Primary Mouse Models of Soft Tissue Sarcoma: Impact of Tumor Mutational Load." International journal of radiation oncology, biology, physics 96.2S (October 2016): E578-E579.
PMID
27675063
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E578
End Page
E579
DOI
10.1016/j.ijrobp.2016.06.2077

Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment.

Authors
Mowery, YM; Patel, K; Olson, AC; Khan, MK; Salama, JK; Salama, AK
MLA Citation
Mowery, YM, Patel, K, Olson, AC, Khan, MK, Salama, JK, and Salama, AK. "Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment." International journal of radiation oncology, biology, physics 96.2S (October 2016): S158-S159.
PMID
27675668
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
S158
End Page
S159
DOI
10.1016/j.ijrobp.2016.06.383

A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All.

Authors
Mowery, YM; Salama, JK
MLA Citation
Mowery, YM, and Salama, JK. "A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All." Journal of oncology practice 12.8 (August 2016): 725-726.
PMID
27511719
Source
epmc
Published In
Journal of Oncology Practice
Volume
12
Issue
8
Publish Date
2016
Start Page
725
End Page
726
DOI
10.1200/jop.2016.014803

Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era.

Stereotactic body radiation therapy (SBRT) utilizing a small number of high-dose radiation therapy fractions continues to expand in clinical application. Although many approaches have been proposed to radiosensitize tumors with conventional fractionation, how these radiosensitizers will translate to SBRT remains largely unknown. Here, we review our current understanding of how SBRT eradicates tumors, including the potential contributions of endothelial cell death and immune system activation. In addition, we identify several new opportunities for radiosensitization generated by the move toward high dose per fraction radiation therapy.

Authors
Moding, EJ; Mowery, YM; Kirsch, DG
MLA Citation
Moding, EJ, Mowery, YM, and Kirsch, DG. "Opportunities for Radiosensitization in the Stereotactic Body Radiation Therapy (SBRT) Era." Cancer journal (Sudbury, Mass.) 22.4 (July 2016): 267-273. (Review)
PMID
27441746
Source
epmc
Published In
Cancer Journal
Volume
22
Issue
4
Publish Date
2016
Start Page
267
End Page
273
DOI
10.1097/ppo.0000000000000203

SU-F-R-15: Establishing Relevant ADC-Based Texture Analysis Metrics for Quantifying Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinoma.

The purpose of this study is to identify texture analysis metrics from apparent diffusion coefficient (ADC) maps that would provide quantifiable changes with treatment in patients with head and neck squamous cell carcinoma (HNSCC). We discerned which imaging metrics were relevant using baseline agreement and variations during early treatment.We retrospectively analyzed diffusion-weighted MRI scans in 9 patients with stages II-IV HNSCC. ADC maps were generated from two baseline scans, performed 1 week apart, and one early treatment scan, obtained during the 2nd week of chemoradiation. Regions of interest (ROI) consisting of primary and nodal disease were drawn on the resampled ADC maps. Four 3D texture matrices describing local and regional relationships between voxel intensities in the ROIs were generated. From these, 38 texture metrics and 7 histogram features were calculated for each patient, including the mean and median ADC. To identify metrics with good agreement between baseline studies, we compared all metrics using the intra-class correlation coefficient (ICC). For metrics with ICC ≥ 0.80, the Wilcoxon signed-rank test was used to test if the difference between the mean of the baselines and the early treatment was non-zero.Nine of the 45 metrics had an ICC ≥ 0.80. Six of these 9 metrics had a p-value < 0.05: run length non-uniformity, ADC median, texture strength, ADC mean, zone percentage, and variance. Only 1 of the 9 metrics remained of interest, after applying the Holm correction to the alpha levels: run length non-uniformity (p = 0.004) in the Gray Level Run Length Matrix.The feasibility of texture analysis is dependent on the baseline agreement of each metric, which disqualifies many texture characteristics. Consequently, only a few metrics are reproducible and qualify for future studies that provide quantitative assessment of early treatment changes for HNSCC.

Authors
Loman, K; Nawrocki, J; Hoang, J; Yoo, D; Chang, Z; Mowery, Y; Li, X; Peterson, B; Brizel, D; Craciunescu, O
MLA Citation
Loman, K, Nawrocki, J, Hoang, J, Yoo, D, Chang, Z, Mowery, Y, Li, X, Peterson, B, Brizel, D, and Craciunescu, O. "SU-F-R-15: Establishing Relevant ADC-Based Texture Analysis Metrics for Quantifying Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinoma." Medical physics 43.6 (June 2016): 3376-.
PMID
28046312
Source
epmc
Published In
Medical physics
Volume
43
Issue
6
Publish Date
2016
Start Page
3376
DOI
10.1118/1.4955787

Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue.

To evaluate the impact of guided meditation and music interventions on patient anxiety, pain, and fatigue during imaging-guided breast biopsy.After giving informed consent, 121 women needing percutaneous imaging-guided breast biopsy were randomized into three groups: (1) guided meditation; (2) music; (3) standard-care control group. During biopsy, the meditation and music groups listened to an audio-recorded, guided, loving-kindness meditation and relaxing music, respectively; the standard-care control group received supportive dialogue from the biopsy team. Immediately before and after biopsy, participants completed questionnaires measuring anxiety (State-Trait Anxiety Inventory Scale), biopsy pain (Brief Pain Inventory), and fatigue (modified Functional Assessment of Chronic Illness Therapy-Fatigue). After biopsy, participants completed questionnaires assessing radiologist-patient communication (modified Questionnaire on the Quality of Physician-Patient Interaction), demographics, and medical history.The meditation and music groups reported significantly greater anxiety reduction (P values < .05) and reduced fatigue after biopsy than the standard-care control group; the standard-care control group reported increased fatigue after biopsy. The meditation group additionally showed significantly lower pain during biopsy, compared with the music group (P = .03). No significant difference in patient-perceived quality of radiologist-patient communication was noted among groups.Listening to guided meditation significantly lowered biopsy pain during imaging-guided breast biopsy; meditation and music reduced patient anxiety and fatigue without compromising radiologist-patient communication. These simple, inexpensive interventions could improve women's experiences during core-needle breast biopsy.

Authors
Soo, MS; Jarosz, JA; Wren, AA; Soo, AE; Mowery, YM; Johnson, KS; Yoon, SC; Kim, C; Hwang, ES; Keefe, FJ; Shelby, RA
MLA Citation
Soo, MS, Jarosz, JA, Wren, AA, Soo, AE, Mowery, YM, Johnson, KS, Yoon, SC, Kim, C, Hwang, ES, Keefe, FJ, and Shelby, RA. "Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue." Journal of the American College of Radiology : JACR 13.5 (May 2016): 526-534.
PMID
26853501
Source
epmc
Published In
Journal of the American College of Radiology
Volume
13
Issue
5
Publish Date
2016
Start Page
526
End Page
534
DOI
10.1016/j.jacr.2015.12.004

A primer on medical education in the United States through the lens of a current resident physician.

Physician training and standards for medical licensure differ widely across the globe. The medical education process in the United States (US) typically involves a minimum of 11 years of formal training and multiple standardized examinations between graduating from secondary school and becoming an attending physician with full medical licensure. Students in the US traditionally enter a 4-year medical school after completing an undergraduate bachelor's degree, in contrast to most other countries where medical training begins after graduation from high school. Medical school seniors planning to practice medicine in the US must complete postgraduate clinical training, referred to as residency, within the specialty of their choosing. The duration of residency varies depending on specialty, typically lasting between 3 and 7 years. For subspecialty fields, additional clinical training is often required in the form of a fellowship. Many experts have called for changes in the medical education system to shorten medical training in the US, and reforms are ongoing in some institutions. However, physician education in the US generally remains a progression from undergraduate premedical coursework to 4 years of medical school, followed by residency training with an optional subspecialty fellowship.

Authors
Mowery, YM
MLA Citation
Mowery, YM. "A primer on medical education in the United States through the lens of a current resident physician." Journal of thoracic disease 7.10 (October 2015): E473-E481.
PMID
26623123
Source
epmc
Published In
Journal of Thoracic Disease
Volume
7
Issue
10
Publish Date
2015
Start Page
E473
End Page
E481
DOI
10.3978/j.issn.2072-1439.2015.10.05

A primer on medical education in the United States through the lens of a current resident physician.

Physician training and standards for medical licensure differ widely across the globe. The medical education process in the United States (US) typically involves a minimum of 11 years of formal training and multiple standardized examinations between graduating from secondary school and becoming an attending physician with full medical licensure. Students in the US traditionally enter a 4-year medical school after completing an undergraduate bachelor's degree, in contrast to most other countries where medical training begins after graduation from high school. Medical school seniors planning to practice medicine in the US must complete postgraduate clinical training, referred to as residency, within the specialty of their choosing. The duration of residency varies depending on specialty, typically lasting between 3 and 7 years. For subspecialty fields, additional clinical training is often required in the form of a fellowship. Many experts have called for changes in the medical education system to shorten medical training in the US, and reforms are ongoing in some institutions. However, physician education in the US generally remains a progression from undergraduate premedical coursework to 4 years of medical school, followed by residency training with an optional subspecialty fellowship.

Authors
Mowery, YM
MLA Citation
Mowery, YM. "A primer on medical education in the United States through the lens of a current resident physician." Annals of translational medicine 3.18 (October 2015): 270-.
PMID
26605316
Source
epmc
Published In
Annals of translational medicine
Volume
3
Issue
18
Publish Date
2015
Start Page
270
DOI
10.3978/j.issn.2305-5839.2015.10.19

Preoperative partial breast

© Springer International Publishing Switzerland, 2016. Partial breast irradiation, treatment focused only on the surgical bed plus a variable margin, has evolved as an ultra-convenient alternative to whole breast irradiation for selected patients with early-stage breast cancer. A number of techniques are available for treatment delivery, ranging from a single intraoperative treatment to one week of twice daily treatments postoperatively. However, concerns of suboptimal cosmetic outcomes have been raised with the highly accessible external-beam technique and linked to large postoperative target volumes. Preoperative radiation, delivered prior to surgical resection, is under investigation as an alternative approach utilizing in situ targeting of a small intact breast tumor to identify the highest-risk regions and reduce the volume of uninvolved breast tissue receiving high radiation doses. Several commonly utilized technologies can be used to deliver preoperative radiation and early efficacy and toxicity reports for this treatment approach are promising. The rationale, treatment delivery techniques, available outcomes data, and ongoing investigations for preoperative partial breast irradiation are described in further depth in the accompanying chapter.

Authors
Mowery, YM; Yu, CX; Horton, JK
MLA Citation
Mowery, YM, Yu, CX, and Horton, JK. "Preoperative partial breast." Short Course Breast Radiotherapy: A Comprehensive Review of Hypofractionation, Partial Breast, and Intra-Operative Irradiation. January 1, 2015. 415-440.
Source
scopus
Publish Date
2015
Start Page
415
End Page
440
DOI
10.1007/978-3-319-24388-7_27

The UK HeartSpare Study (Stage IB): Randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery

Authors
Mowery, YM; Blitzblau, RC
MLA Citation
Mowery, YM, and Blitzblau, RC. "The UK HeartSpare Study (Stage IB): Randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery." Breast Diseases: A Year Book Quarterly 26.3 (2015): 237-239.
Source
crossref
Published In
Breast Diseases: A Year Book Quarterly
Volume
26
Issue
3
Publish Date
2015
Start Page
237
End Page
239
DOI
10.1016/j.breastdis.2015.07.001

Whole-breast radiation therapy: the long and short of it.

Authors
Mowery, YM; Blitzblau, RC
MLA Citation
Mowery, YM, and Blitzblau, RC. "Whole-breast radiation therapy: the long and short of it." International journal of radiation oncology, biology, physics 90.5 (December 2014): 990-992.
PMID
25539364
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Issue
5
Publish Date
2014
Start Page
990
End Page
992
DOI
10.1016/j.ijrobp.2014.10.028

TU-F-12A-03: Using 18F-FDG-PET-CT and Deformable Registration During Head-And-Neck Cancer (HNC) Intensity Modulated Radiotherapy (IMRT) to Predict Treatment Response.

To evaluate the effect of deformable vs. rigid registration of pre-treatment 18F-FDG-PET-CT to intra-treatment 18F-FDG-PET-CT on different standardized uptake value (SUV) parameters and investigate which parameters correlate best with post-treatment response in patients undergoing IMRT for HNC.Pre-treatment and intra-treatment PET-CT (after 20Gy) scans were acquired, in addition to a 12 week post-treatment PET-CT to assess treatment response. Primary and lymph node gross tumor volumes (GTV_PRI and GTV_LN) were contoured on the pre-treatment CT. These contours were then mapped to intra-treatment PET images via rigid and deformable registration. Absolute changes from pre- to intra-treatment scans for rigid and deformable registration were extracted for the following parameters: SUV_MAX, SUV_MEAN, SUV_20%, SUV_40%, and SUV_60% (SUV_X% is the minimum SUV to the highest-intensity X% volume).Thirty-eight patients were evaluated, with 27 available for classification as complete or incomplete response (CR/ICR). The pre-treatment average tumor volumes for the patients were 24.05cm3 for GTV_PRI and 23.4cm3 for GTV_LN. For GTV_PRI, there was no statistically significant difference between rigid vs. deformable registration across all ΔSUV parameters. For GTV_LN contours, all parameters were significantly different except for ΔSUV_MAX. For deformably-registered GTV_PRI, changes in the following metrics were significantly different for CR vs. ICR: SUV_MEAN(p=0.003), SUV_20%(p=0.02), SUV_40%(p=0.02), and SUV_60%(p=0.008). The following cutoff values separated CR from ICR with high sensitivity and specificity: ΔSUV_MEAN=1.49, ΔSUV_20%=2.39, ΔSUV_40%=1.80 and ΔSUV_60%=1.31. Corresponding areas under the Receiver Operating Characteristics curve were 0.90, 0.81, 0.81, and 0.85, respectively.Rigidly and deformably registered contours yielded statistically similar SUV parameters for GTV_PRI, but not GTV_LN. This implies that neither registration should be solely relied upon for nodal GTVs. Of the four SUV parameters found to be predictive of CR vs. ICR, SUV_MEAN was the strongest. Preliminary results show promise for using intra-treatment 18F-FDG-PET-CT with deformable registration to predict treatment response.

Authors
Vergalasova, I; Mowery, Y; Yoo, D; Brizel, D; Das, S
MLA Citation
Vergalasova, I, Mowery, Y, Yoo, D, Brizel, D, and Das, S. "TU-F-12A-03: Using 18F-FDG-PET-CT and Deformable Registration During Head-And-Neck Cancer (HNC) Intensity Modulated Radiotherapy (IMRT) to Predict Treatment Response." Medical physics 41.6 (June 2014): 480-481.
PMID
28037720
Source
epmc
Published In
Medical physics
Volume
41
Issue
6
Publish Date
2014
Start Page
480
End Page
481
DOI
10.1118/1.4889358

Clinical aspects of monoclonal B-cell lymphocytosis.

BACKGROUND: Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic precursor condition for chronic lymphocytic leukemia (CLL). It is defined by the presence of small clones of aberrant B cells in the peripheral blood, with a total B-cell count below the threshold for diagnosis of CLL (<5.0x10(9) cells/L). METHODS: The authors review current literature on the prevalence of MBL, and the clinical course of this CLL precursor condition, and recommended management for individuals with MBL. RESULTS: MBL occurs in approximately 4% to 5% of healthy adults. While most cases of CLL are preceded by MBL, progression to leukemia requiring CLL treatment occurs in only 1% to 2% of individuals with MBL per year. The absolute B-cell count is most strongly associated with progression, and patients with low-count MBL identified in population screening studies rarely develop CLL. Studies are ongoing to better define the relationship between MBL and CLL and to identify prognostic indicators that predict which patients will progress to CLL. Given their elevated risk of developing malignancy, individuals with clinical MBL should be monitored at least annually for progressive lymphocytosis and signs or symptoms of CLL. CONCLUSIONS: Many of the epidemiologic and genetic factors associated with MBL development and its progression to CLL have not yet been identified. However, ongoing studies by many research groups are aimed at answering these questions to facilitate management of individuals with this premalignant condition. In addition, active investigation of MBL will likely yield new insights into the biology of CLL, potentially identifying new therapeutic targets for this incurable disease.

Authors
Mowery, YM; Lanasa, MC
MLA Citation
Mowery, YM, and Lanasa, MC. "Clinical aspects of monoclonal B-cell lymphocytosis." Cancer Control 19.1 (January 2012): 8-17. (Review)
PMID
22143058
Source
pubmed
Published In
Cancer control : journal of the Moffitt Cancer Center
Volume
19
Issue
1
Publish Date
2012
Start Page
8
End Page
17

Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin.

Receptor-recognized forms of α₂ -macroglobulin (α₂ M) bind to cell surface-associated GRP78 and initiate pro-proliferative and anti-apoptotic signaling. Ligation of GRP78 with α₂ M also upregulates TFII-I, which binds to the GRP78 promoter and enhances GRP78 synthesis. In addition to its transcriptional functions, cytosolic TFII-I regulates agonist-induced Ca(2+) entry. In this study we show that down regulation of TFII-I gene expression by RNAi profoundly impairs its cell surface expression and anti-apoptotic signaling as measured by significant reduction of GRP78, Bcl-2, and cyclin D1 in 1-Ln and DU-145 human prostate cancer cells stimulated with α₂ M. In contrast, this treatment significantly increases levels of the pro-apoptotic proteins p53, p27, Bax, and Bak and causes DNA fragmentation. Furthermore, down regulation of TFII-I expression activates agonist-induced Ca(2+) entry. In plasma membrane lysates p-PLCγ1, TRPC3, GRP78, MTJ1, and caveolin co-immunoprecipitate with TFII-I suggesting multimeric complexes of these proteins. Consistent with this hypothesis, down regulating TFII-I, MTJ1, or GRP78 expression by RNAi greatly attenuates cell surface expression of TFII-I. In conclusion, we demonstrate that not only does cell surface GRP78 regulate apoptosis, but it also regulates Ca(2+) homeostasis by controlling cell surface localization of TFII-I.

Authors
Misra, UK; Mowery, YM; Gawdi, G; Pizzo, SV
MLA Citation
Misra, UK, Mowery, YM, Gawdi, G, and Pizzo, SV. "Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin." J Cell Biochem 112.6 (June 2011): 1685-1695.
PMID
21503958
Source
pubmed
Published In
Journal of Cellular Biochemistry
Volume
112
Issue
6
Publish Date
2011
Start Page
1685
End Page
1695
DOI
10.1002/jcb.23083

Cell surface ATP synthase: A potential target for anti-angiogenic therapy

Since the presence of F 1 F 0 adenosine triphosphate (ATP) synthase was discovered on the surface of human cells, numerous studies have elucidated new functions for this molecule that classically functions as part of the electron transport chain in mitochondria. Like mitochondrial ATP synthase, the cell surface form of this molecule functions as an energy-producing proton pump, coupling the production of extracellular ATP with the transport of protons outside the cell. ATP synthase also acts as an endothelial cell surface receptor for angiostatin, which has led several groups to examine this molecule as a target for inhibiting angiogenesis. Given its involvement in proton transport and the pH-dependent activity of angiostatin and antibodies directed against it, ATP synthase likely functions in part to regulate pH for endothelial cells existing in an acidic microenvironment. In addition, it catalyzes the synthesis and hydrolysis of ATP in the extracellular milieu, potentially affecting purinergic signaling. ATP synthase also plays a role in endothelial cell signaling in response to flow-induced shear stress. Recently, ATP synthase on the surface of endothelial cells has been identified as the receptor for two additional proteins: coupling factor 6 and endothelial monocyte-activating polypeptide II. This chapter will focus on the role of endothelial cell surface ATP synthase in angiogenesis, shear stress response, and as a receptor. © Springer Science+Business Media B.V. 2010.

Authors
Mowery, YM; Pizzo, SV
MLA Citation
Mowery, YM, and Pizzo, SV. "Cell surface ATP synthase: A potential target for anti-angiogenic therapy." (December 1, 2010): 139-159. (Chapter)
Source
scopus
Publish Date
2010
Start Page
139
End Page
159
DOI
10.1007/978-90-481-3435-9_9

LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.

B-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. The mean concentration of LMP-420 required to induce 50% cytotoxicity (ED50) at 72 h was 245 n. LMP-420-induced time- and dose-dependent apoptosis, as shown by annexin V staining, caspase activation and DNA fragmentation. These changes were associated with decreased expression of anti-apoptotic proteins Mcl-1, Bcl-xL and Bcl-2. CLL cells from patients with poor prognostic indicators showed LMP-420 sensitivity equal to that for cells from patients with favorable characteristics. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of stimulated CLL cells. Gene expression profiling indicated that the mechanism of action of LMP-420 may involve suppression of nuclear factor-kappaB and immune response pathways in CLL cells. LMP-420 had minimal effects on normal peripheral blood mononuclear cell, B- and T-cell function, and hematopoietic colony formation. Our data suggest that LMP-420 may be a useful treatment for CLL with negligible hematologic toxicities.

Authors
Mowery, YM; Weinberg, JB; Kennedy, MN; Bond, KM; Moore, JO; Lanasa, MC; Gockerman, JP; Diehl, LF; Pizzo, SV; Cianciolo, GJ; Friedman, DR
MLA Citation
Mowery, YM, Weinberg, JB, Kennedy, MN, Bond, KM, Moore, JO, Lanasa, MC, Gockerman, JP, Diehl, LF, Pizzo, SV, Cianciolo, GJ, and Friedman, DR. "LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells." Leukemia 24.9 (September 2010): 1580-1587.
PMID
20613784
Source
pubmed
Published In
Leukemia
Volume
24
Issue
9
Publish Date
2010
Start Page
1580
End Page
1587
DOI
10.1038/leu.2010.150

Stall encodes an ADAMTS metalloprotease and interacts genetically with Delta in Drosophila ovarian follicle formation.

Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene function, both within and outside the ovary, for follicle individualization, stalk cell intercalation, and oocyte localization. We have identified the stl transcript as CG3622 and confirmed the presence of three alternatively spliced isoforms, contrary to current genome annotation. Here we show that the gene is expressed in both ovarian and brain tissues, which is consistent with previous evidence of an ovary nonautonomous function. On the basis of amino acid sequence, stl encodes a metalloprotease similar to the "a disintegrin and metalloprotease with thrombospondin" (ADAMTS) family. Although stl mutant ovaries fail to maintain the branched structure of the fusome and periodically show improperly localized oocytes, stl mutants do not alter oocyte determination. Within the ovary, stl is expressed in pupal basal stalks and in adult somatic cells of the posterior germarium and the follicular poles. Genetically, stl exhibits a strong mutant interaction with Delta (Dl), and Dl mutant ovaries show altered stl expression patterns. Additionally, a previously described genetic interactor, daughterless, also modulates stl expression in the somatic ovary and may do so directly in its capacity as a basic helix-loop-helix (bHLH) transcription factor. We propose a complex model of long-range extraovarian signaling through secretion or extracellular domain shedding, together with local intraovarian protein modification, to explain the dual sites of Stl metalloprotease function in oogenesis.

Authors
Ozdowski, EF; Mowery, YM; Cronmiller, C
MLA Citation
Ozdowski, EF, Mowery, YM, and Cronmiller, C. "Stall encodes an ADAMTS metalloprotease and interacts genetically with Delta in Drosophila ovarian follicle formation." Genetics 183.3 (November 2009): 1027-1040.
PMID
19752215
Source
epmc
Published In
Genetics
Volume
183
Issue
3
Publish Date
2009
Start Page
1027
End Page
1040
DOI
10.1534/genetics.109.107367

The antitumorigenic trifecta.

The laboratory of Judah Folkman identified the potent endogenous antiangiogenic protein angiostatin in 1994.(1) In this issue of Blood, Lee and colleagues propose 2 new mechanisms of action for angiostatin that may represent promising targets for new cancer therapeutics.(2).

Authors
Mowery, YM; Pizzo, SV
MLA Citation
Mowery, YM, and Pizzo, SV. "The antitumorigenic trifecta." Blood 114.9 (August 2009): 1727-1728.
PMID
19713480
Source
epmc
Published In
Blood
Volume
114
Issue
9
Publish Date
2009
Start Page
1727
End Page
1728
DOI
10.1182/blood-2009-06-226233

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis.

Binding of activated α(2)-macroglobulin to GRP78 on the surface of human prostate cancer cells promotes proliferation by activating signaling cascades. Autoantibodies directed against the activated α(2)-macroglobulin binding site in the NH(2)-terminal domain of GRP78 are receptor agonists, and their presence in the sera of cancer patients is a poor prognostic indicator. We now show that antibodies directed against the GRP78 COOH-terminal domain inhibit [(3)H]thymidine uptake and cellular proliferation while promoting apoptosis as measured by DNA fragmentation, Annexin V assay, and clonogenic assay. These antibodies are receptor antagonists blocking autophosphorylation and activation of GRP78. Using 1-LN and DU145 prostate cancer cell lines and A375 melanoma cells, which express GRP78 on their cell surface, we show that antibodies directed against the COOH-terminal domain of GRP78 up-regulate the tumor suppressor protein p53. By contrast, antibody directed against the NH(2)-terminal domain of GRP78 shows negligible effects on p53 expression. PC-3 prostate cancer cells, which do not express GRP78 on their cell surface, are refractory to the effects of anti-GRP78 antibodies directed against either the COOH- or NH(2)-terminal domains. However, overexpression of GRP78 in PC-3 cells causes translocation of GRP78 to the cell surface and promotes apoptosis when these cells are treated with antibody directed against its COOH-terminal domain. Silencing GRP78 or p53 expression by RNA interference significantly blocked the increase in p53 induced by antibodies. Antibodies directed against the COOH-terminal domain may play a therapeutic role in cancer patients whose tumors trigger the production of autoantibodies directed against the NH(2)-terminal domain of GRP78.

Authors
Misra, UK; Mowery, Y; Kaczowka, S; Pizzo, SV
MLA Citation
Misra, UK, Mowery, Y, Kaczowka, S, and Pizzo, SV. "Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis." Mol Cancer Ther 8.5 (May 2009): 1350-1362.
PMID
19417154
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
8
Issue
5
Publish Date
2009
Start Page
1350
End Page
1362
DOI
10.1158/1535-7163.MCT-08-0990

Targeting cell surface F1F0 ATP synthase in cancer therapy.

Authors
Mowery, YM; Pizzo, SV
MLA Citation
Mowery, YM, and Pizzo, SV. "Targeting cell surface F1F0 ATP synthase in cancer therapy." Cancer biology & therapy 7.11 (November 8, 2008): 1836-1838.
PMID
18981725
Source
epmc
Published In
Cancer Biology and Therapy
Volume
7
Issue
11
Publish Date
2008
Start Page
1836
End Page
1838
DOI
10.4161/cbt.7.11.7155

Targeting cell surface F1F0 ATP synthase in cancer therapy

Authors
Mowery, YM; Pizzo, SV
MLA Citation
Mowery, YM, and Pizzo, SV. "Targeting cell surface F1F0 ATP synthase in cancer therapy." Cancer Biology and Therapy 7.11 (November 1, 2008): 1837-1839.
Source
scopus
Published In
Cancer Biology and Therapy
Volume
7
Issue
11
Publish Date
2008
Start Page
1837
End Page
1839

Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.

The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface, blocking cellular proliferation. To examine the specificity of this interaction, we generated monoclonal antibodies (mAb) directed against ATP synthase. mAb directed against the beta-catalytic subunit of ATP synthase (MAb3D5AB1) inhibits the activity of the F(1) domain of ATP synthase and recognizes the catalytic beta-subunit of ATP synthase. We located the antibody recognition site of MAb3D5AB1 in domains containing the active site of the beta-subunit. MAb3D5AB1 also binds to purified Escherichia coli F(1) with an affinity 25-fold higher than the affinity of angiostatin for this protein. MAb3D5AB1 inhibits the hydrolytic activity of F(1) ATP synthase at lower concentrations than angiostatin. Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the endothelial cell surface in acidic conditions, the typical tumor microenvironment where cell surface ATP synthase exhibits greater activity. MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial cells exposed to low extracellular pH. Neither angiostatin nor MAb3D5AB1 showed an antiangiogenic effect in the corneal neovascularization assay; however, both were effective in the low-pH environment of the chicken chorioallantoic membrane assay. Thus, MAb3D5AB1 shows angiostatin-like properties superior to angiostatin and may be exploited in cancer chemotherapy.

Authors
Chi, SL; Wahl, ML; Mowery, YM; Shan, S; Mukhopadhyay, S; Hilderbrand, SC; Kenan, DJ; Lipes, BD; Johnson, CE; Marusich, MF; Capaldi, RA; Dewhirst, MW; Pizzo, SV
MLA Citation
Chi, SL, Wahl, ML, Mowery, YM, Shan, S, Mukhopadhyay, S, Hilderbrand, SC, Kenan, DJ, Lipes, BD, Johnson, CE, Marusich, MF, Capaldi, RA, Dewhirst, MW, and Pizzo, SV. "Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase." Cancer Res 67.10 (May 15, 2007): 4716-4724.
PMID
17510399
Source
pubmed
Published In
Cancer Research
Volume
67
Issue
10
Publish Date
2007
Start Page
4716
End Page
4724
DOI
10.1158/0008-5472.CAN-06-1094

Bariatric surgery for severely obese adolescents.

A 1991 National Institutes of Health Consensus Conference concluded that severely obese adults could be eligible for bariatric surgery if they had a body mass index (BMI) > or =35 kg/m(2) with or > or =40 kg/m(2) without obesity comorbidity. It was thought at that time that there were inadequate data to support bariatric surgery in severely obese adolescents. An estimated 25% of children in the United States are obese, a number that has doubled over a 30-year period. Very little information has been published on the subject of obesity surgery in adolescents. Therefore we reviewed our 20-year database on bariatric surgery in adolescents. Severely obese adolescents, ranging from 12 to less than 18 years of age, were considered eligible for bariatric surgery according to the National Institutes of Health adult criteria. Gastroplasty was the procedure of choice in the initial 3 years of the study followed by gastric bypass, which was found to be significantly more effective for weight loss in adults. Distal gastric bypass (D-GBP) was used in extremely obese patients (BMI > or =60 kg/m(2)) before 1992 and long-limb gastric bypass (LL-GBP) was used for superobese patients (BMI > or =50 kg/m(2)) after 1992. Laparoscopic gastric bypass was used after 2000. Thirty-three adolescents (27 white, 6 black; 19 females, 14 males) underwent the following bariatric operations between 1981 and June 2001: horizontal gastroplasty in one, vertical banded gastroplasty in two, standard gastric bypass in 17 (2 laparoscopic), LL-GBP in 10, and D-GBP in three. Mean BMI was 52 +/- 11 kg/m(2) (range 38 to 91 kg/m(2)), and mean age was 16 +/- 1 years (range 12.4 to 17.9 years). Preoperative comorbid conditions included the following: type II diabetes mellitus in two patients, hypertension in 11, pseudotumor cerebri in three, gastroesophageal reflux in five, sleep apnea in six, urinary incontinence in two, polycystic ovary syndrome in one, asthma in one, and degenerative joint disease in 11. There were no operative deaths or anastomotic leaks. Early complications included pulmonary embolism in one patient, major wound infection in one, minor wound infections in four, stomal stenoses (endoscopically dilated) in three, and marginal ulcers (medically treated) in four. Late complications included small bowel obstruction in one and incisional hernias in six patients. There were two late sudden deaths (2 years and 6 years postoperatively), but these were unlikely to have been caused by the bariatric surgical procedure. Revision procedures included one D-GBP to gastric bypass for malnutrition and one gastric bypass to LL-GBP for inadequate weight loss. Regain of most or all of the lost weight was seen in five patients at 5 to 10 years after surgery; however, significant weight loss was maintained in the remaining patients for up to 14 years after surgery. Comorbid conditions resolved at 1 year with the exception of hypertension in two patients, gastroesophageal reflux in two, and degenerative joint disease in seven. Self-image was greatly enhanced; eight patients have married and have children, five patients have completed college, and one patient is currently in college. Severe obesity is increasing rapidly in adolescents and is associated with significant comorbidity and social stigmatization. Bariatric surgery in adolescents is safe and is associated with significant weight loss, correction of obesity comorbidity, and improved self-image and socialization. These data strongly support obesity surgery for those unfortunate individuals who may have difficulty obtaining insurance coverage based on the 1991 National Institutes of Health Consensus Conference statement.

Authors
Sugerman, HJ; Sugerman, EL; DeMaria, EJ; Kellum, JM; Kennedy, C; Mowery, Y; Wolfe, LG
MLA Citation
Sugerman, HJ, Sugerman, EL, DeMaria, EJ, Kellum, JM, Kennedy, C, Mowery, Y, and Wolfe, LG. "Bariatric surgery for severely obese adolescents." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 7.1 (January 2003): 102-107.
PMID
12559191
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
7
Issue
1
Publish Date
2003
Start Page
102
End Page
107
DOI
10.1016/s1091-255x(02)00125-7

Training the novice in laparoscopy. More challenge is better.

BACKGROUND: Virtual reality simulation is effective in training the novice to perform basic laparoscopic skills. METHODS: Using the Minimally Invasive Surgery Training--Virtual Reality (MIST-VR) trainer, 27 honors high school students were tested at the easy level, prospectively randomized to eight training sessions at the easy (group A, n = 14) or medium (group B, n = 13) level, then retested at the easy level. RESULTS: Both groups were statistically similar at baseline. All scores improved significantly (50.1% to 81.3%) over the period of training (p < 0.05). Although the group A scores were significantly better than the group B scores throughout training (p < 0.05), on final testing at the easy level, group B surpassed group A for all the tasks except TransferPlace (p = 0.054). CONCLUSIONS: Virtual simulation is an effective laparoscopic training method for the novice, providing significant improvement in skill levels over a relatively short period. More challenging training seems to predict greater improvement over time and better final skill levels.

Authors
Ali, MR; Mowery, Y; Kaplan, B; DeMaria, EJ
MLA Citation
Ali, MR, Mowery, Y, Kaplan, B, and DeMaria, EJ. "Training the novice in laparoscopy. More challenge is better." Surgical endoscopy 16.12 (December 2002): 1732-1736.
PMID
12140638
Source
epmc
Published In
Surgical Endoscopy
Volume
16
Issue
12
Publish Date
2002
Start Page
1732
End Page
1736
DOI
10.1007/s00464-002-8850-6
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