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Article ; Online: Expansion of T Cells with Interleukin-21 for Adoptive Immunotherapy of Murine Mammary Carcinoma.

Zoon, Christine K / Wan, Wen / Graham, Laura / Bear, Harry D

International journal of molecular sciences

2017 Volume 18, Issue 2

Abstract: We previously demonstrated that culturing antigen-sensitized draining lymph node (DLN) lymphocytes from BALB/c mice in interleukin (IL)-7/15 after activation with bryostatin/ionomycin (B/I) is superior to culture in IL-2 for expansion, differentiation to ...

Abstract	We previously demonstrated that culturing antigen-sensitized draining lymph node (DLN) lymphocytes from BALB/c mice in interleukin (IL)-7/15 after activation with bryostatin/ionomycin (B/I) is superior to culture in IL-2 for expansion, differentiation to cluster of differentiation (CD)8+ cells and anti-tumor activity. We sought to determine whether the substitution or addition of IL-21 to culture had a similar effect. DLN lymphocytes were antigen-sensitized with 4T1 mammary carcinoma 10 days prior to harvest, activated with B/I, and expanded in culture for 7 days with either IL-2, IL-21, IL-2/21, IL-7/15, or IL-7/15/21. Cellular expansion, phenotype, interferon (IFN)-γ responses, and in vivo anti-tumor activity were compared. We found that T cells grown in IL7/15/21 demonstrated significantly greater lymphocyte expansion than IL-2, IL-21, IL-2/21, and IL-7/15 (38.4-fold vs. 5.5, 6.6, 9.5, and 23.9-fold, respectively). Of these expanded cells, IL-7/15/21 significantly expanded the greatest percentage of CD8+ cells (67.1% vs. 22.2%, 47.2%, 47.4%, and 55.3%, respectively), and the greatest number of T central memory cells (T
MeSH term(s)	Animals ; Biomarkers ; Disease Models, Animal ; Female ; Immunophenotyping ; Immunotherapy, Adoptive/methods ; Interleukins/pharmacology ; Lymphocyte Activation ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mice ; Phenotype ; Primary Cell Culture ; T-Lymphocyte Subsets/drug effects ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Tumor Burden/immunology
Chemical Substances	Biomarkers ; Interleukins ; interleukin-21
Language	English
Publishing date	2017-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18020270
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Article ; Online: The role of margin status and reexcision in local recurrence following breast conservation surgery.

Adams, Barbara J / Zoon, Christine K / Stevenson, Christina / Chitnavis, Padma / Wolfe, Luke / Bear, Harry D

Annals of surgical oncology

2013 Volume 20, Issue 7, Page(s) 2250–2255

Abstract: Introduction: Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is ... ...

Abstract	Introduction: Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is performed only if tumor is at inked margin or with extensive disease close to multiple margins. The purpose of this study was to determine rates of reexcision and recurrences among BCS patients using this policy. Methods: We performed an institutional review board-approved retrospective analysis of BCS patients who underwent surgery between January 2001 and June 2005. We identified patients who had a second breast excision within 8 weeks of the first, and those patients with an IBTR. Clinical and pathologic features of patients' tumors were reviewed. Results: We identified 543 patients who underwent BCS, 84 patients (15.5 %) underwent reexcision for margin status. The crude IBTR rate was 3.4 %, and the 5-year local recurrence-free survival of the reexcised group was 90.6 % compared with 97.4 % in the non-reexcised group (p = 0.0097). Of the 64 reexcision patients, 6 (9.4 %) had an IBTR versus 12 (2.6 %) of the 459 non-reexcised patients (p = 0.0151). Discussion: Our reexcision rate is low compared with other reports. This results from a policy that defines "no tumor on ink" as an adequate margin for BCS, and the use of selective irradiation boosts based on margins assessed by our pathologists. Our local recurrence rate compares favorably with those seen in other studies while minimizing the need for additional operations. A higher IBTR rate after reexcision likely reflects tumor biology.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/metabolism ; Breast Neoplasms/surgery ; Breast Neoplasms/therapy ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/surgery ; Carcinoma, Ductal, Breast/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Neoplasm Recurrence, Local/therapy ; Neoplasm, Residual ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Reoperation ; Retrospective Studies
Chemical Substances	Antineoplastic Agents ; Receptors, Estrogen ; Receptors, Progesterone ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-012-2831-3
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Article ; Online: The importance of considering competing risks in recurrence analysis of intracranial meningioma.

Mirian, Christian / Jensen, Lasse Rehné / Juratli, Tareq A / Maier, Andrea Daniela / Torp, Sverre H / Shih, Helen A / Morshed, Ramin A / Young, Jacob S / Magill, Stephen T / Bertero, Luca / Stummer, Walter / Spille, Dorothee Cäcilia / Brokinkel, Benjamin / Oya, Soichi / Miyawaki, Satoru / Saito, Nobuhito / Proescholdt, Martin / Kuroi, Yasuhiro / Gousias, Konstantinos /

Simon, Matthias / Moliterno, Jennifer / Prat-Acin, Ricardo / Goutagny, Stéphane / Prabhu, Vikram C / Tsiang, John T / Wach, Johannes / Güresir, Erdem / Yamamoto, Junkoh / Kim, Young Zoon / Lee, Joo Ho / Koshy, Matthew / Perumal, Karthikeyan / Baskaya, Mustafa K / Cannon, Donald M / Shrieve, Dennis C / Suh, Chang-Ok / Chang, Jong Hee / Kamenova, Maria / Straumann, Sven / Soleman, Jehuda / Eyüpoglu, Ilker Y / Catalan, Tony / Lui, Austin / Theodosopoulos, Philip V / McDermott, Michael W / Wang, Fang / Guo, Fuyou / Góes, Pedro / de Paiva Neto, Manoel Antonio / Jamshidi, Aria / Komotar, Ricardo / Ivan, Michael / Luther, Evan / Souhami, Luis / Guiot, Marie-Christine / Csonka, Tamás / Endo, Toshiki / Barrett, Olivia Claire / Jensen, Randy / Gupta, Tejpal / Patel, Akash J / Klisch, Tiemo J / Kim, Jun Won / Maiuri, Francesco / Barresi, Valeria / Tabernero, María Dolores / Skyrman, Simon / Broechner, Anders / Bach, Mathias Jacobsen / Law, Ian / Scheie, David / Kristensen, Bjarne Winther / Munch, Tina Nørgaard / Meling, Torstein / Fugleholm, Kåre / Blanche, Paul / Mathiesen, Tiit

Journal of neuro-oncology

2024 Volume 166, Issue 3, Page(s) 503–511

Abstract: Background: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of ... ...

Abstract	Background: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. Methods: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. Results: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). Conclusion: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.
MeSH term(s)	Humans ; Aged ; Meningioma/pathology ; Meningeal Neoplasms/pathology ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Risk Assessment
Language	English
Publishing date	2024-02-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-024-04572-y
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Article: Psychiatric aspects of child and adolescent obesity: a review of the past 10 years.

Zametkin, Alan J / Zoon, Christine K / Klein, Hannah W / Munson, Suzanne

Journal of the American Academy of Child and Adolescent Psychiatry

2004 Volume 43, Issue 2, Page(s) 134–150

Abstract: Objective: To review the past 10 years of published research on psychiatric aspects of child and adolescent obesity and highlight information mental health professionals need for preventing obesity in youths and diagnosing and treating it.: Method: ... ...

Abstract	Objective: To review the past 10 years of published research on psychiatric aspects of child and adolescent obesity and highlight information mental health professionals need for preventing obesity in youths and diagnosing and treating it. Method: Researchers performed computerized and manual searches of the literature and summarized the most relevant articles. Results: The growing epidemic of child and adolescent obesity deserves attention for its immediate mental health and long-term medical complications. Mental health professionals working with obese youths should be aware of recent advances in neuroscience, genetics, and etiologies associated with obesity. Those who assess and treat obese youth should view obesity as a chronic disease. Currently, no approved pharmacological or surgical approaches exist to treat childhood obesity. Conclusions: Health care providers should focus on modest weight-loss goals that correlate with significant health benefits. The most effective treatments include substantial parental involvement. Mental health professionals should help obese children build self-esteem to help them lead full lives regardless of weight.
MeSH term(s)	Adolescent ; Body Mass Index ; Child ; Female ; Health Status ; Humans ; Obesity/epidemiology ; Obesity/psychology ; Obesity/therapy ; Prevalence ; Self Concept
Language	English
Publishing date	2004-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	392535-3
ISSN	1527-5418 ; 0890-8567
ISSN (online)	1527-5418
ISSN	0890-8567
DOI	10.1097/00004583-200402000-00008
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Article ; Online: Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells.

Payne, Kyle K / Zoon, Christine K / Wan, Wen / Marlar, Khin / Keim, Rebecca C / Kenari, Mehrab Nasiri / Kazim, A Latif / Bear, Harry D / Manjili, Masoud H

Breast cancer research and treatment

2013 Volume 142, Issue 1, Page(s) 45–57

Abstract: Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding ... ...

Abstract	Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding and reprogramming tumor-sensitized lymphocytes, ex vivo, yielded T memory (Tm) cells as well as activated CD25+ NKT cells and NK cells. The presence of activated CD25+ NKT and NK cells rendered reprogrammed T cells resistant to MDSC-mediated suppression, and adoptive cellular therapy (ACT) of reprogrammed lymphocytes protected the host from tumor development and relapse. Here, we performed a pilot study to determine the clinical applicability of our protocol using peripheral blood mononuclear cells (PBMCs) of breast cancer patients, ex vivo. We show that bryostatin 1 and ionomycin combined with IL-2, IL-7, and IL-15 can expand and reprogram tumor-sensitized PBMCs. Reprogrammed lymphocytes contained activated CD25+ NKT and NK cells as well as Tm cells and displayed enhanced reactivity against HER-2/neu in the presence of MDSCs. The presence of activated NKT cells was highly correlated with the rescue of anti-HER-2/neu immune responses from MDSC suppression. Ex vivo blockade experiments suggest that the NKG2D pathway may play an important role in overcoming MDSC suppression. Our results show the feasibility of reprogramming tumor-sensitized immune cells, ex vivo, and provide rationale for ACT of breast cancer patients.
MeSH term(s)	Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Bryostatins/pharmacology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Humans ; Immunotherapy, Adoptive ; Interleukin-15/pharmacology ; Interleukin-2/pharmacology ; Interleukin-7/pharmacology ; Ionomycin/pharmacology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Activation/immunology ; Lymphocyte Subsets/drug effects ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/metabolism ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/metabolism ; Neoplasm Staging ; Receptor, ErbB-2/immunology ; Receptor, ErbB-2/metabolism ; Tumor Burden
Chemical Substances	Bryostatins ; Interleukin-15 ; Interleukin-2 ; Interleukin-7 ; bryostatin 1 (37O2X55Y9E) ; Ionomycin (56092-81-0) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-10-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-013-2733-5
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Article ; Online: Current molecular diagnostics of breast cancer and the potential incorporation of microRNA.

Zoon, Christine K / Starker, Elizabeth Q / Wilson, Arianne M / Emmert-Buck, Michael R / Libutti, Steven K / Tangrea, Michael A

Expert review of molecular diagnostics

2009 Volume 9, Issue 5, Page(s) 455–467

Abstract: Although comprehensive molecular diagnostics and personalized medicine have sparked excitement among researchers and clinicians, they have yet to be fully incorporated into today's standard of care. This is despite the discovery of disease-related ... ...

Abstract	Although comprehensive molecular diagnostics and personalized medicine have sparked excitement among researchers and clinicians, they have yet to be fully incorporated into today's standard of care. This is despite the discovery of disease-related oncogenes, tumor-suppressor genes and protein biomarkers, as well as other biological anomalies related to cancer. Each year, new tests are released that could potentially supplement or surpass standard methods of diagnosis, including serum, protein and gene expression analyses. All of these novel approaches have shown great promise, but initial enthusiasm has diminished as difficulties in reproducibility, expense, standardization and proof of significance beyond current protocols have emerged. This review will focus on current and novel molecular diagnostic tools applied to breast cancer with special attention to the exciting new field of microRNA analysis.
MeSH term(s)	Biomarkers, Tumor/genetics ; Breast Neoplasms/diagnosis ; Breast Neoplasms/metabolism ; Early Detection of Cancer ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Medical Oncology/methods ; Medical Oncology/trends ; MicroRNAs/metabolism ; Models, Biological ; Molecular Diagnostic Techniques ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism
Chemical Substances	Biomarkers, Tumor ; MicroRNAs ; Receptors, Estrogen ; Receptors, Progesterone ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2009-06-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1586/erm.09.25
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Article ; Online: The Effect on Surgical Complications of Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer: NRG Oncology/NSABP Protocol B-40.

Annals of surgical oncology

2017 Volume 24, Issue 7, Page(s) 1853–1860

Abstract: Background: NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not ... ...

Abstract	Background: NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not receive bev. Methods: A total of 1206 women with HER2-negative operable breast cancer were randomly assigned to receive one of three different docetaxel-plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks) for the first 6 of 8 cycles and for 10 doses postoperatively. Surgical complications were assessed from date of surgery through 24 months following study entry. Results: Early surgical complications were significantly more frequent in the bev group (25.4 vs. 18.9%; trend test p = 0.008), but most were grade 1-2. Early noninfectious wound dehiscences were infrequent and not significantly different (5.4 vs. 3.1%; trend test p = 0.15). Long-term noninfectious wound complications were significantly higher for patients receiving bev (11.8 vs. 5.1%; trend test p = 0.0007), but the incidence of grade ≥3 wound dehiscence was low in both groups (<1%). Among 193 patients undergoing expander or implant reconstructions, 19 (19.6%) of 97 in the bev-receiving group versus 10 (10.4%) of 96 in the non-bev group had grade ≥3 complications (Pearson, p = 0.11). Conclusions: Overall, adding bev increased surgical complications, but most serious complications were not significantly increased. In particular, the need for surgical intervention in patients undergoing breast reconstruction with prosthetic implants was higher with bev but was not statistically significantly different. With precautions, bev can be used safely perioperatively in patients undergoing surgery for breast cancer.
MeSH term(s)	Anthracyclines/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bevacizumab/administration & dosage ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/adverse effects ; Mastectomy/adverse effects ; Prognosis ; Prospective Studies ; Surgical Wound Infection/etiology ; Survival Rate ; Taxoids/administration & dosage
Chemical Substances	Anthracyclines ; Taxoids ; docetaxel (15H5577CQD) ; Bevacizumab (2S9ZZM9Q9V)
Language	English
Publishing date	2017-07
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-016-5662-9
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Article ; Online: Expansion of T Cells with Interleukin-21 for Adoptive Immunotherapy of Murine Mammary Carcinoma.

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Article ; Online: The role of margin status and reexcision in local recurrence following breast conservation surgery.

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Article ; Online: The importance of considering competing risks in recurrence analysis of intracranial meningioma.

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Article: Psychiatric aspects of child and adolescent obesity: a review of the past 10 years.

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Article ; Online: Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells.

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Article ; Online: Current molecular diagnostics of breast cancer and the potential incorporation of microRNA.

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Article ; Online: The Effect on Surgical Complications of Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer: NRG Oncology/NSABP Protocol B-40.

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