المؤلفون: Upasana Ray, Debarshi Roy, Ling Jin, Prabhu Thirusangu, Julie Staub, Yinan Xiao, Eleftheria Kalogera, Andrea E. Wahner Hendrickson, Grace D. Cullen, Krista Goergen, Ann L. Oberg, Viji Shridhar

المصدر: Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-16 (2021)

مصطلحات موضوعية: Ovarian cancer, metastasis, Group III phospholipase A2, chemosensitivity, autophagy, primary cilia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. Methods CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. Results Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. Conclusions Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-9966Test

الوصول الحر: https://doaj.org/article/c51f205913f048ecae91afeecbaec90fTest

المؤلفون: Shi-Wen Jiang, Haibin Chen, Sean Dowdy, Alex Fu, John Attewell, Eleftheria Kalogera, Ronny Drapkin, Karl Podratz, Russell Broaddus, Jinping Li

المصدر: International Journal of Molecular Sciences, Vol 14, Iss 11, Pp 22655-22677 (2013)

مصطلحات موضوعية: HE4, transcription, splice variants, gene expression, endometrial cancer, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/14/11/22655Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/28129aff1b8b4814a7ffdb5f0825f989Test

المؤلفون: Upasana Ray (3763864), Debarshi Roy (10920043), Ling Jin (133762), Prabhu Thirusangu (10920046), Julie Staub (10920049), Yinan Xiao (7336949), Eleftheria Kalogera (10920052), Andrea E. Wahner Hendrickson (10920055), Grace D. Cullen (10920058), Krista Goergen (277812), Ann L. Oberg (217897), Viji Shridhar (278465)

مصطلحات موضوعية: Biophysics, Biochemistry, Microbiology, Cell Biology, Genetics, Molecular Biology, Physiology, Pharmacology, Biotechnology, Cancer, Hematology, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Ovarian cancer, metastasis, Group III phospholipase A2, chemosensitivity, autophagy, primary cilia

الوصف: Additional file 1.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_Group_III_phospholipase_A2_downregulation_attenuated_survival_and_metastasis_in_ovarian_cancer_and_promotes_chemo-sensitization/14728585Test

الإتاحة: https://doi.org/10.6084/m9.figshare.14728585.v1Test

المؤلفون: Debarshi Roy, Prabhu Thirusangu, Ann L. Oberg, Krista M. Goergen, Viji Shridhar, Andrea E. Wahner Hendrickson, Grace D. Cullen, Upasana Ray, Yinan Xiao, Ling Jin, Julie Staub, Eleftheria Kalogera

المصدر: Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-16 (2021)
Journal of Experimental & Clinical Cancer Research : CR

مصطلحات موضوعية: Cancer Research, autophagy, Cell Survival, Pyridines, medicine.disease_cause, Metastasis, Mice, primary cilia, Downregulation and upregulation, Microscopy, Electron, Transmission, Ovarian cancer, medicine, Animals, Humans, metastasis, MTT assay, Viability assay, Neoplasm Metastasis, Cytotoxicity, RC254-282, Cell Proliferation, Platinum, Ovarian Neoplasms, Chemistry, Research, Group III Phospholipases A2, Lipogenesis, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Lipid Droplets, medicine.disease, Gene Expression Regulation, Neoplastic, chemosensitivity, Group III phospholipase A2, Oncology, Cancer research, Quinolines, Heterografts, Female, CRISPR-Cas Systems, Carcinogenesis

الوصف: Background Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. Methods CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. Results Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. Conclusions Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2312f39716829d872e4f2d1f69a840aTest
https://doaj.org/article/c51f205913f048ecae91afeecbaec90fTest

المؤلفون: Eleftheria Kalogera, Gregg Nelson, Sean C. Dowdy

المصدر: Journal of Gynecologic Surgery. 37:122-126

مصطلحات موضوعية: Obstetrics and Gynecology, Surgery

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::83feb3fca1ae8c8182e4975aebe0ad6eTest
https://doi.org/10.1089/gyn.2021.0007Test

المؤلفون: Ayssa Teles Abrao Trad, Prajakta Tamhane, Amy L. Weaver, Mary V. Baker, Sue L. Visscher, Bijan J. Borah, Eleftheria Kalogera, John B. Gebhart, Emanuel C. Trabuco

المصدر: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and ObstetricsREFERENCES. 159(3)

مصطلحات موضوعية: Analgesics, Opioid, Pain, Postoperative, Obstetrics and Gynecology, Humans, Female, General Medicine, Length of Stay, Medicare, Enhanced Recovery After Surgery, United States, Aged, Retrospective Studies

الوصف: To assess the effect of Enhanced Recovery After Surgery (ERAS) with and without liposomal bupivacaine (LB) on opioid use, hospital length of stay (LOS), costs, and morbidity of women undergoing sacrocolpopexy.Retrospective cohort of women who underwent abdominal sacrocolpopexy between April 1, 2009 and November 30, 2017. Costs for relevant healthcare services were determined by assigning 2017 charges multiplied by 2017 Medicare Cost Report's cost to charge ratios. Outcomes were compared among periods with multivariable regression models adjusted for age, American Society of Anesthesiologists score, and concurrent hysterectomy and posterior repair.Patients were subdivided into pre-ERAS (G1, n = 128), post-ERAS (G2, n = 83), and post-ERAS plus LB (G3, n = 91). The proportion of patients needing opioids during postoperative days 0-2 was significantly less for G3 (75.8%) compared with G1 (97.7%) and G2 (92.8%); P 0.001). The median morphine equivalent units (MEU) with interquartile ranges, mean LOS, and adjusted mean standardized costs were significantly lower in G3 compared with the other two groups (35 [20-75] vs. 67 [31-109], and 60 [30-122] MEUs; 1.8 vs. 2.3 vs. 2.9 days; and $2391, $2975, and $3844, for G3, G2, and G1, respectively; P 0.001).Implementation of an ERAS pathway led to significant decreases in opioid use, LOS, and costs. Supplementation with LB further improved these measures.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b0b876a34df0a335950fa3854ac9305Test
https://pubmed.ncbi.nlm.nih.gov/35598156Test

المؤلفون: Yinan Xiao, Viji Shridhar, Julie Staub, Chaolin Deng, Sayantani Sarkar Bhattacharya, Upasana Ray, Ling Jin, Xiaoling Fang, Eleftheria Kalogera, Haotian Xu, Ye Guan, Prabhu Thirusangu

المصدر: Oncogene

مصطلحات موضوعية: Cancer Research, Programmed cell death, Phosphofructokinase-2, Pyridines, Apoptosis, Biology, Article, Carboplatin, chemistry.chemical_compound, Targeted therapies, Endometrial cancer, Downregulation and upregulation, Cell Line, Tumor, Autophagy, Genetics, medicine, Chemotherapy, Humans, Molecular Biology, Protein kinase B, Cell Proliferation, Cisplatin, Cell growth, TOR Serine-Threonine Kinases, Xenograft Model Antitumor Assays, Endometrial Neoplasms, Gene Expression Regulation, Neoplastic, chemistry, Drug Resistance, Neoplasm, Cell culture, Quinolines, Cancer research, Female, Signal Transduction, medicine.drug

الوصف: The advanced or recurrent endometrial cancer (EC) has a poor prognosis because of chemoresistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a glycolytic enzyme, is overexpressed in a variety of human cancers and plays important roles in promoting tumor cell growth. Here, we showed that high expression of PFKFB3 in EC cell lines is associated with chemoresistance. Pharmacological inhibition of PFKFB3 with PFK158 and or genetic downregulation of PFKFB3 dramatically suppressed cell proliferation and enhanced the sensitivity of EC cells to carboplatin (CBPt) and cisplatin (Cis). Moreover, PFKFB3 inhibition resulted in reduced glucose uptake, ATP production, and lactate release. Notably, we found that PFK158 with CBPt or Cis exerted strong synergistic antitumor activity in chemoresistant EC cell lines, HEC-1B and ARK-2 cells. We also found that the combination of PFK158 and CBPt/Cis induced apoptosis- and autophagy-mediated cell death through inhibition of the Akt/mTOR signaling pathway. Mechanistically, we found that PFK158 downregulated the CBPt/Cis-induced upregulation of RAD51 expression and enhanced CBPt/Cis-induced DNA damage as demonstrated by an increase in γ-H2AX levels in HEC-1B and ARK-2 cells, potentially revealing a means to enhance PFK158-induced chemosensitivity. More importantly, PFK158 treatment, either as monotherapy or in combination with CBPt, led to a marked reduction in tumor growth in two chemoresistant EC mouse xenograft models. These data suggest that PFKFB3 inhibition alone or in combination with standard chemotherapy may be used as a novel therapeutic strategy for improved therapeutic efficacy and outcomes of advanced and recurrent EC patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9889ad4045dd12b8f7e423ae5438c349Test
https://doi.org/10.1038/s41388-020-01621-4Test

المؤلفون: Eleftheria Kalogera

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::d52c66c194752d14e7054696b686c5a6Test
https://doi.org/10.1016/b978-0-323-91208-2.00005-6Test

المؤلفون: Chahin Achtari, Alon D. Altman, Jamie N. Bakkum-Gamez, Victoria Bennett, Geetu Bhandoria (Prakash), Steven Bisch, Hans D. de Boer, Laurent Bollag, Adela Cope, Kevin M. Elias, William John Fawcett, Emily Fay, Gretchen E. Glaser, Sarah P. Huepenbecker, Maria D. Iniesta, Chris Jones, Eleftheria Kalogera, Leigh Kelliher, Zaraq Khan, Fleurisca J. Korteweg, Amanika Kumar, Jenna K. Lovely, Larissa A. Meyer, Ester Miralpeix, Basile Pache, Magali Robert, Michael J. Scott, Pranav Shah, T.S. Shylasree, Henriette Smid-Nanninga, Diana Encalada Soto, Pervez Sultan, Carolyn Swenson, Jolyn S. Taylor, Pat Trudeau, Leense S. Wagenaar, Sumer K. Wallace, Simrit K. Warring, Lena Wijk

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::1723a6f6f8c401ec0acc7b9e7d1e22b0Test
https://doi.org/10.1016/b978-0-323-91208-2.09991-1Test

المؤلفون: Eleftheria Kalogera, Sean C. Dowdy

المصدر: Clinical Obstetrics & Gynecology. 62:656-665

مصطلحات موضوعية: medicine.medical_specialty, MEDLINE, Audit, 03 medical and health sciences, Gynecologic Surgical Procedures, 0302 clinical medicine, medicine, Humans, Pain Management, Patient Reported Outcome Measures, Intensive care medicine, Enhanced recovery after surgery, Analgesics, Pain, Postoperative, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Perioperative, Acute Pain, Colorectal surgery, Systematic review, Opioid, Acute postoperative pain, Female, Enhanced Recovery After Surgery, business, medicine.drug

الوصف: Enhanced recovery pathways were first developed in colorectal surgery and have since been adapted to other surgical subspecialties including gynecologic surgery. Mounting evidence has shown that the adoption of a standardized perioperative pathway based on evidence-based literature reduces length of hospital stay, reduces cost, reduces opioid requirements with stable to improved pain scores, and accelerates return to normal function as measured by validated patient reported outcomes measurements. The many elements of enhanced recovery may be distilled into 3 concepts: (1) optimizing nutrition before and after surgery, recognizing that nutritional status directly impacts healing; (2) opioid-sparing analgesia, considering the current American prescription opioid crisis and the importance of pain control to regaining functional recovery; and (3) maintenance of euvolemia before, during, and after surgery. Evidence supporting enhanced recovery is presented with reference to international guidelines which were formed based on systematic reviews. Change management and the use of auditing are discussed to assure that patients derive the greatest improvement in surgical outcomes from implementation of an enhanced recovery pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efbf5905bd80aa92acaeed475ddde0c1Test
https://doi.org/10.1097/grf.0000000000000475Test