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Article ; Online: The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine.

O'Connell, Cailin / VandenHeuvel, Sabrina / Kamat, Aparna / Raghavan, Shreya / Godin, Biana

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical ... ...

Abstract	Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical features of OvCa, including staging and current techniques for diagnosis and therapy. Further, the important role of proteases in OvCa progression and dissemination is described. Proteases contribute to tumor angiogenesis, remodeling of extracellular matrix, migration and invasion, major processes in OvCa pathology. Multiple proteases, such as metalloproteinases, trypsin, cathepsin and others, are overexpressed in the tumor tissue. Presence of these catabolic enzymes in OvCa tissue can be exploited for improving early diagnosis and therapeutic options in advanced cases. Nanomedicine, being on the interface of molecular and cellular scales, can be designed to be activated by proteases in the OvCa microenvironment. Various types of protease-enabled nanomedicines are described and the studies that focus on their diagnostic, therapeutic and theranostic potential are reviewed.
MeSH term(s)	Carcinoma, Ovarian Epithelial ; Endopeptidases ; Female ; Humans ; Nanomedicine ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Tumor Microenvironment
Chemical Substances	Endopeptidases (EC 3.4.-)
Language	English
Publishing date	2022-09-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179981
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Article ; Online: Macrophage Checkpoint Nanoimmunotherapy Has the Potential to Reduce Malignant Progression in Bioengineered

VandenHeuvel, Sabrina N / Chau, Eric / Mohapatra, Arpita / Dabbiru, Sameera / Roy, Sanjana / O'Connell, Cailin / Kamat, Aparna / Godin, Biana / Raghavan, Shreya A

ACS applied bio materials

2024

Abstract: Most ovarian carcinoma (OvCa) patients present with advanced disease at the time of diagnosis. Malignant, metastatic OvCa is invasive and has poor prognosis, exposing the need for improved therapeutic targeting. High CD47 (OvCa) and SIRPα (macrophage) ... ...

Abstract	Most ovarian carcinoma (OvCa) patients present with advanced disease at the time of diagnosis. Malignant, metastatic OvCa is invasive and has poor prognosis, exposing the need for improved therapeutic targeting. High CD47 (OvCa) and SIRPα (macrophage) expression has been linked to decreased survival, making this interaction a significant target for therapeutic discovery. Even so, previous attempts have fallen short, limited by CD47 antibody specificity and efficacy. Macrophages are an important component of the OvCa tumor microenvironment and are manipulated to aid in cancer progression via CD47-SIRPα signaling. Thus, we have leveraged lipid-based nanoparticles (LNPs) to design a therapy uniquely situated to home to phagocytic macrophages expressing the SIRPα protein in metastatic OvCa. CD47-SIRPα presence was evaluated in patient histological sections using immunohistochemistry. 3D tumor spheroids generated on a hanging drop array with OVCAR3 high-grade serous OvCa and THP-1-derived macrophages created a representative model of cellular interactions involved in metastatic OvCa. Microfluidic techniques were employed to generate LNPs encapsulating SIRPα siRNA (siSIRPα) to affect the CD47-SIRPα signaling between the OvCa and macrophages. siSIRPα LNPs were characterized for optimal size, charge, and encapsulation efficiency. Uptake of the siSIRPα LNPs by macrophages was assessed by Incucyte. Following 48 h of 25 nM siSIRPα treatment, OvCa/macrophage heterospheroids were evaluated for SIRPα knockdown, platinum chemoresistance, and invasiveness. OvCa patient tumors and
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.4c00076
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Article ; Online: Editor's Note: The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer.

Kamat, Aparna A / Fletcher, Mavis / Gruman, Lynn M / Mueller, Peter / Lopez, Adriana / Landen, Charles N / Han, Liz / Gershenson, David M / Sood, Anil K

Clinical cancer research : an official journal of the American Association for Cancer Research

2021 Volume 27, Issue 15, Page(s) 4455

Language	English
Publishing date	2021-07-24
Publishing country	United States
Document type	Journal Article ; Expression of Concern
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-2121
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Zs.A 4223: Show issues

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Article: Laparoscopic Allograft Spacer Placement to Minimize Bowel Dose During Re-irradiation with Interstitial Brachytherapy.

Dalwadi, Shraddha / Suri, Anuj / Kamat, Aparna / Butler, E Brian / Farach, Andrew M

Cureus

2019 Volume 11, Issue 10, Page(s) e5958

Abstract: In primary or re-irradiation of gynecologic malignancies, achieving optimal dosimetry with adjacent normal tissue becomes challenging. Surgical spacers are tissue-equivalent materials placed within the patient to protect organs at risk from long-term ... ...

Abstract	In primary or re-irradiation of gynecologic malignancies, achieving optimal dosimetry with adjacent normal tissue becomes challenging. Surgical spacers are tissue-equivalent materials placed within the patient to protect organs at risk from long-term radiation effects and are commonly used in prostate cancer. We report the use of an allograft mesh to protect adhesed bowel from high-dose radiation for definitive treatment of recurrent endometrial cancer. An 88-year-old female was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer after she developed urinary frequency, hesitancy, and hematuria. She underwent neoadjuvant chemoradiation, followed by laparoscopic hysterectomy with bilateral salpingo-oophorectomy and adjuvant vaginal cuff brachytherapy. She developed 1.8 cm bilateral vaginal cuff recurrence and was dispositioned for interstitial brachytherapy. An allograft mesh spacer was placed laparoscopically before repeat, high dose rate brachytherapy to protect nearby structures. Dose-escalation was achieved without compromising normal tissue constraints. The patient tolerated the procedure without evidence of long-term toxicity at one year. Multidisciplinary discussion may help identify patients who would benefit from spacer placement before select dose-escalated radiation therapy. Laparoscopic allograft mesh is one of many types of surgical spacers available for such patients.
Language	English
Publishing date	2019-10-22
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.5958
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Article ; Online: Erythropoeisis-stimulating agents (ESAs) in cervix cancer: The "black box" paradox.

Kamat, Aparna A / Coleman, Robert L

Cancer biology & therapy

2009 Volume 8, Issue 1, Page(s) 18–20

MeSH term(s)	Anemia/etiology ; Anemia/prevention & control ; Erythropoietin/therapeutic use ; Female ; Hematinics/therapeutic use ; Hemoglobins/metabolism ; Humans ; Quality of Life ; Recombinant Proteins ; Uterine Cervical Neoplasms/blood ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/radiotherapy
Chemical Substances	Hematinics ; Hemoglobins ; Recombinant Proteins ; epoetin beta ; Erythropoietin (11096-26-7) ; hemoglobin B (9041-75-2)
Language	English
Publishing date	2009-01-29
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2146305-0
ISSN	1555-8576 ; 1538-4047
ISSN (online)	1555-8576
ISSN	1538-4047
DOI	10.4161/cbt.8.1.7520
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Zs.A 5887: Show issues

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Article: Correction: Focal Adhesion Kinase Targeting Using

Halder, Jyotsnabaran / Kamat, Aparna A / Landen, Charles N / Han, Liz Y / Lutgendorf, Susan K / Lin, Yvonne G / Merritt, William M / Jennings, Nicholas B / Chavez-Reyes, Arturo / Coleman, Robert L / Gershenson, David M / Schmandt, Rosemarie / Cole, Steven W / Lopez-Berestein, Gabriel / Sood, Anil K

Clinical cancer research : an official journal of the American Association for Cancer Research

2019 Volume 25, Issue 10, Page(s) 3194

Language	English
Publishing date	2019-03-29
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-1132
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Article ; Online: Author Correction: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.

Thaker, Premal H / Han, Liz Y / Kamat, Aparna A / Arevalo, Jesusa M / Takahashi, Rie / Lu, Chunhua / Jennings, Nicholas B / Armaiz-Pena, Guillermo / Bankson, James A / Ravoori, Murali / Merritt, William M / Lin, Yvonne G / Mangala, Lingegowda S / Kim, Tae Jin / Coleman, Robert L / Landen, Charles N / Li, Yang / Felix, Edward / Sanguino, Angela M /

Newman, Robert A / Lloyd, Mary / Gershenson, David M / Kundra, Vikas / Lopez-Berestein, Gabriel / Lutgendorf, Susan K / Cole, Steven W / Sood, Anil K

Nature medicine

2021 Volume 27, Issue 12, Page(s) 2246

Language	English
Publishing date	2021-11-19
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-021-01566-5
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 39: Show issues

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Article: The merits of vascular targeting for gynecologic malignancies.

Kamat, Aparna A / Sood, Anil K

Current oncology reports

2005 Volume 7, Issue 6, Page(s) 444–450

Abstract: Neovascularization is an early and critical step in tumor development and progression. Tumor vessels are distinct from their normal counterparts morphologically as well as at a molecular level. Recent studies on factors involved in tumor vascular ... ...

Abstract	Neovascularization is an early and critical step in tumor development and progression. Tumor vessels are distinct from their normal counterparts morphologically as well as at a molecular level. Recent studies on factors involved in tumor vascular development have identified new therapeutic targets for inhibiting tumor neovascularization and thus tumor progression. However, the process of tumor blood vessel formation is complex, and each tumor exhibits unique features in its vasculature. An understanding of the relative contribution of various pathways in the development of tumor vasculature is critical for developing effective and selective therapeutic approaches. Several such agents are currently in clinical trials, and many others are under development. In this review, the mechanisms and factors involved in tumor blood vessel formation are discussed. In addition, selected novel classes of antivascular therapies, including those targeting tumor endothelial cells and other components of the tumor vasculature, are summarized.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Female ; Genital Neoplasms, Female/blood supply ; Genital Neoplasms, Female/pathology ; Humans ; Microcirculation ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/pathology
Chemical Substances	Angiogenesis Inhibitors
Language	English
Publishing date	2005-04-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2057359-5
ISSN	1523-3790
ISSN	1523-3790
DOI	10.1007/s11912-005-0009-x
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Zs.A 5521: Show issues

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Article ; Online: A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families.

Kimble, Danielle C / Lach, Francis P / Gregg, Siobhan Q / Donovan, Frank X / Flynn, Elizabeth K / Kamat, Aparna / Young, Alice / Vemulapalli, Meghana / Thomas, James W / Mullikin, James C / Auerbach, Arleen D / Smogorzewska, Agata / Chandrasekharappa, Settara C

Human mutation

2017 Volume 39, Issue 2, Page(s) 237–254

Abstract: Fanconi anemia (FA) is a rare recessive DNA repair deficiency resulting from mutations in one of at least 22 genes. Two-thirds of FA families harbor mutations in FANCA. To genotype patients in the International Fanconi Anemia Registry (IFAR) we employed ... ...

Abstract	Fanconi anemia (FA) is a rare recessive DNA repair deficiency resulting from mutations in one of at least 22 genes. Two-thirds of FA families harbor mutations in FANCA. To genotype patients in the International Fanconi Anemia Registry (IFAR) we employed multiple methodologies, screening 216 families for FANCA mutations. We describe identification of 57 large deletions and 261 sequence variants, in 159 families. All but seven families harbored distinct combinations of two mutations demonstrating high heterogeneity. Pathogenicity of the 18 novel missense variants was analyzed functionally by determining the ability of the mutant cDNA to improve the survival of a FANCA-null cell line when treated with MMC. Overexpressed pathogenic missense variants were found to reside in the cytoplasm, and nonpathogenic in the nucleus. RNA analysis demonstrated that two variants (c.522G > C and c.1565A > G), predicted to encode missense variants, which were determined to be nonpathogenic by a functional assay, caused skipping of exons 5 and 16, respectively, and are most likely pathogenic. We report 48 novel FANCA sequence variants. Defining both variants in a large patient cohort is a major step toward cataloging all FANCA variants, and permitting studies of genotype-phenotype correlations.
MeSH term(s)	Cell Line ; Fanconi Anemia/genetics ; Fanconi Anemia/pathology ; Fanconi Anemia Complementation Group A Protein/genetics ; Fluorescent Antibody Technique ; Humans ; Mutation, Missense/genetics
Chemical Substances	Fanconi Anemia Complementation Group A Protein
Language	English
Publishing date	2017-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1126646-6
ISSN	1098-1004 ; 1059-7794
ISSN (online)	1098-1004
ISSN	1059-7794
DOI	10.1002/humu.23366
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Zs.A 3586: Show issues

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Article ; Online: Non-16/18 high-risk HPV infection predicts disease persistence and progression in women with an initial interpretation of LSIL.

Lyons, Yasmin A / Kamat, Aparna A / Zhou, Haijun / Mody, Dina R / Schwartz, Mary R / Hobday, Christopher / Ge, Yimin

Cancer cytopathology

2015 Volume 123, Issue 7, Page(s) 435–442

Abstract: Background: The current management strategy for women with low-grade squamous intraepithelial lesions (LSILs) is inefficient and expensive because of the inability to identify patients at high risk for disease progression. The current study was designed ...

Abstract	Background: The current management strategy for women with low-grade squamous intraepithelial lesions (LSILs) is inefficient and expensive because of the inability to identify patients at high risk for disease progression. The current study was designed to determine the genotypic patterns of human papillomavirus (HPV) associated with the persistence and progression of cervical lesions in women with an initial interpretation of LSIL. Methods: One hundred sixty-seven women with LSIL on Papanicolaou tests collected between December 1, 2009 and March 30, 2011 were studied. HPV DNA was extracted from residual SurePath specimens, genotypes were determined with a DNA microarray containing 40 HPV genotype probes, and microarray data were confirmed by sequencing. Follow-up Papanicolaou tests and/or biopsies were performed within a 20- to 46-month period after the initial diagnosis. Results: Ninety-seven of the 167 cases with follow-up results were included in the study. Compared with the women with a regressed cervical lesion, those with a persistent cervical lesion (PCL) were significantly more commonly infected with high-risk human papillomavirus (HR-HPV) genotypes (P < .01) and particularly with non-16/18 HR-HPV genotypes (P < .05). The PCL group also had a significantly higher average number of HR-HPV genotypes and non-16/18 HPV genotypes per specimen (P < .01). Infection with HPV-16/18 genotypes was not significantly associated with the persistence or progression of cervical lesions. Conclusions: Infection with non-16/18 HR-HPV genotypes but not with HPV-16/18 genotypes was a strong predictor of the persistence and progression of cervical disease upon follow-up. Genotyping solely for HPV-16/18 would miss the majority of patients with LSIL who progress to high-grade squamous intraepithelial lesions. Pooled HR-HPV tests provide a better predictive value than HPV-16/18 genotyping alone in guiding the clinical management of patients with LSIL.
MeSH term(s)	Adult ; Age Factors ; Carcinoma, Squamous Cell/epidemiology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cervical Intraepithelial Neoplasia/genetics ; Cervical Intraepithelial Neoplasia/pathology ; Cervical Intraepithelial Neoplasia/physiopathology ; China/epidemiology ; Chronic Disease ; Cohort Studies ; DNA, Viral/genetics ; Disease Progression ; Female ; Genotype ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Humans ; Middle Aged ; Neoplasm Invasiveness/pathology ; Papanicolaou Test ; Papillomavirus Infections/epidemiology ; Papillomavirus Infections/genetics ; Papillomavirus Infections/pathology ; Predictive Value of Tests ; Prevalence ; Retrospective Studies ; Risk Assessment ; Vaginal Smears ; Young Adult
Chemical Substances	DNA, Viral
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2594979-2
ISSN	1934-6638 ; 1934-662X
ISSN (online)	1934-6638
ISSN	1934-662X
DOI	10.1002/cncy.21549
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