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  1. AU="Franklin, Renty B"
  2. AU="Tetri, Laura H"
  3. AU="Badve, Sunil V"
  4. AU=Zhang Yinan
  5. AU="Piquero, Nicole Leeper"
  6. AU="Russo, Giorgio Ivan" AU="Russo, Giorgio Ivan"
  7. AU=Pourdowlat Guitti
  8. AU="Frisenda, Riccardo"
  9. AU=Palmucci Stefano

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  1. Artikel: Zinc: The Wonder Drug for the Treatment of Carcinomas.

    Costello, Leslie C / Franklin, Renty B

    Acta scientific cancer biology

    2020  Band 4, Heft 5, Seite(n) 33–39

    Abstract: Evidence is evolving that support the relationship that all carcinomas exhibit the following important relationships: The malignant cells exhibit a significant decreased zinc compared to the normal cells. The higher zinc levels that exist in the normal ... ...

    Abstract Evidence is evolving that support the relationship that all carcinomas exhibit the following important relationships: The malignant cells exhibit a significant decreased zinc compared to the normal cells. The higher zinc levels that exist in the normal cells are cytotoxic in the malignant cells. The decrease in zinc is due to the down regulation of the ZIP-family zinc uptake transporter. These cells are as "ZIP-deficient/decreased zinc" malignancies. This provides a target for a chemotherapy that can restore the high zinc levels that will manifest cytotoxic effects in the malignant cells. In order to achieve this, a vehicle that facilitates the uptake and accumulation of zinc in the ZIP-deficient cells is required. The zinc ionophore, clioquinol, exhibits the properties that will provide these requirements. This is demonstrated by the treatment of a patient with 3% Clioquinol Cream, which successfully suppressed the progression of androgen-dependent prostate cancer. This treatment should also be efficacious for pancreatic cancer, liver cancer, breast cancer, thyroid cancer, kidney cancer, stomach cancer, gall bladder cancer, and lung cancer; which are carcinomas that exhibit decreased zinc. Thus, it is appropriate to describe that "Zinc is the wonder drug for the treatment of carcinomas".
    Sprache Englisch
    Erscheinungsdatum 2020-04-27
    Erscheinungsland India
    Dokumenttyp Journal Article
    DOI 10.31080/ascb.2020.04.0223
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: A Proposed Efficacious Treatment with Clioquinol (Zinc Ionophore) and Cabergoline (Prolactin Dopamine Agonist) for the Treatment of Terminal Androgen-independent Prostate Cancer. Why and How?

    Costello, Leslie C / Franklin, Renty B

    Journal of clinical research in oncology

    2018  Band 2, Heft 1

    Abstract: All cases of prostate cancer exhibit the hallmark condition of marked decrease in zinc in malignancy compared to the high zinc levels in the normal and benign prostate. There exists no reported corroborated case of prostate cancer in which malignancy ... ...

    Abstract All cases of prostate cancer exhibit the hallmark condition of marked decrease in zinc in malignancy compared to the high zinc levels in the normal and benign prostate. There exists no reported corroborated case of prostate cancer in which malignancy exhibits the high zinc levels that exist in the normal prostate acinar epithelium. The decrease in zinc is achieved by the downregulation of ZIP1 zinc transporter, which prevents the uptake and accumulation of cytotoxic zinc levels. Thus, prostate cancer is a "ZIP1-deficient" malignancy. Testosterone and prolactin are the major hormones that similarly regulate the growth, proliferation, metabolism, and functional activities of the acinar epithelial cells in the peripheral zone (the site of development and progression of malignancy). Testosterone regulation provides the basis for androgen ablation treatment of advanced prostate cancer, which leads to the development of terminal androgen-independent malignancy. Androgen-independent malignancy progresses under the influence of prolactin. These relationships provide the basis for the prevention and treatment of advanced prostate cancer. Clioquinol (zinc ionophore; 5-chloro-7-iodoquinolin-8-ol) is employed to facilitate zinc transport and accumulation in the ZIP1-deficient malignant cells and induce cytotoxic effects. Cabergoline (dopamine agonist) is employed to decrease prolactin production and its role in the progression of androgen-independent malignancy. We propose a clioquinol/cabergoline treatment regimen that will be efficacious for aborting terminal advanced prostate cancer. FDA policies permit this treatment regimen to be employed for these patients.
    Sprache Englisch
    Erscheinungsdatum 2018-02-05
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2639-8230
    ISSN (online) 2639-8230
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Energy Dispersive X-Ray Fluorescence Zn/Fe Ratiometric Determination of Zinc Levels in Expressed Prostatic Fluid: A Direct, Non-Invasive and Highly Accurate Screening for Prostate Cancer.

    Costello, Leslie C / Franklin, Renty B

    Acta scientific cancer biology

    2018  Band 2, Heft 9, Seite(n) 20–26

    Abstract: Prostate specific antigen (PSA) does not provide the reliability that is required for the accurate urology screening of prostate cancer (PCa). Consequently, there has been a major focus and search for a simple, rapid, direct, preferably non-invasive, and ...

    Abstract Prostate specific antigen (PSA) does not provide the reliability that is required for the accurate urology screening of prostate cancer (PCa). Consequently, there has been a major focus and search for a simple, rapid, direct, preferably non-invasive, and highly accurate biomarker and procedure for the urology screening for prostate cancer. Virtually all PCa cases exhibit a marked decrease in zinc in prostate tissue and in prostatic fluid. This is a hallmark "signature" clinical characteristic for all prostate cancers, which provides the clinical basis for zinc screening of PCa. Energy dispersive x-ray fluorescence (EDXRF) of zinc levels in expressed prostatic fluid (EPF) provides > 90% accuracy for the identification of prostate cancer vs normal/benign prostate. An energy dispersive x-ray fluorescence (EDXRF) Zn/Fe ratiometric analysis of expressed prostatic fluid (EPF) can provide > 90% accuracy for the identification of prostate cancer vs normal/benign prostate. This will be achieved by direct EDXRF analysis of a "drop" of EPF directly deposited on a filter paper disc during the urology digital rectal examination of the subject. Interfering and confounding conditions that besiege PSA do not exist in the EDXRF Zn/Fe radiometric analyses. This report reviews the basis for zinc analysis for PCA, provides the supporting evidence that EDXRF Zn/Fe ratiometric analysis of EPF will provide a simple, rapid, direct, non-invasive, and highly accurate biomarker and procedure for the urology screening for prostate cancer.
    Sprache Englisch
    Erscheinungsdatum 2018-10-10
    Erscheinungsland India
    Dokumenttyp Journal Article
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: The implications of the hypocitricemic response to surgery and the role of liver function and hepatocyte metabolism: An important, but neglected, clinical relationship.

    Costello, Leslie C / Franklin, Renty B

    Journal of liver research, disorders & therapy

    2018  Band 4, Heft 3, Seite(n) 114–119

    Abstract: Reported studies more than forty years ago established that all surgery patients exhibit a marked postoperative hypocitricemia within one day following surgery and persists for seven days and longer. Animals also exhibit the postoperative hypocitricemia. ...

    Abstract Reported studies more than forty years ago established that all surgery patients exhibit a marked postoperative hypocitricemia within one day following surgery and persists for seven days and longer. Animals also exhibit the postoperative hypocitricemia. The hypocitricemia results from increased liver clearance of plasma citrate, in which the hepatocytes become capable of transporting and utilizing citrate from plasma. This represents a physiologic/metabolic response during the patient recovery from surgery. The extensive hypocitricemia in response to surgery is not manifested by known citricemic hormones, but is initiated via an unidentified putative endocrine hypocitricemic hormone. In addition to the importance relating to surgery patients, the surgical hypocitricemic effects, along with the liver and hepatic cell effects, will impact virtually all human and animal clinical and experimental studies that include surgical intervention; including the conclusions and translational clinical implications. Unfortunately, the hypocitricemic response to surgery has been ignored for the past forty years, and most contemporary clinicians and biomedical investigators are not aware of this clinical relationship. The intent of this review is to inform members of the medical community of the established hypocitricemic response to surgery and the important role of liver clearance and hepatocyte metabolism of plasma citrate; which, hopefully, will generate interest and research that should be integrated into contemporary issues that involve surgical intervention.
    Sprache Englisch
    Erscheinungsdatum 2018-06-08
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2471-1381
    ISSN (online) 2471-1381
    DOI 10.15406/jlrdt.2018.04.00112
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Testosterone, prolactin, and oncogenic regulation of the prostate gland. A new concept: Testosterone-independent malignancy is the development of prolactin-dependent malignancy!

    Costello, Leslie C / Franklin, Renty B

    Oncology reviews

    2018  Band 12, Heft 2, Seite(n) 356

    Abstract: Hormone-independent malignancy is a major issue of morbidity and deaths that confronts prostate cancer. Despite decades of research, the oncogenic and hormonal implications in the development and progression of prostate malignancy remain mostly ... ...

    Abstract Hormone-independent malignancy is a major issue of morbidity and deaths that confronts prostate cancer. Despite decades of research, the oncogenic and hormonal implications in the development and progression of prostate malignancy remain mostly speculative. This is largely due to the absence and/or lack of consideration by contemporary clinicians and biomedical investigators regarding the established implications of the co-regulation of testosterone and prolactin in the development, maintenance, metabolism and functions of the prostate gland. Especially relevant is the major metabolic function of production of high levels of citrate by the peripheral zone acinar epithelial cells. Citrate production, along with growth and proliferation by these cells, is regulated by co-existing testosterone and prolactin signaling pathways; and by the oncogenic down-regulation of ZIP1 transporter/zinc/citrate in the development of malignancy. These relationships had not been considered in the issues of hormonedependent malignancy. This review provides the relevant background that has established the dual role of testosterone and prolactin regulation of the prostate gland; which is essential to address the implications in the oncogenic development and progression of hormone-dependent malignancy. The oncogenic factor along with testosterone-dependent and prolactin-dependent relationships leads to the plausible concept that androgen ablation for the treatment of testosteronedependent malignancy results in the development of
    Sprache Englisch
    Erscheinungsdatum 2018-07-04
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2390302-8
    ISSN 1970-5565 ; 1970-5565 ; 1970-5557
    ISSN (online) 1970-5565
    ISSN 1970-5565 ; 1970-5557
    DOI 10.4081/oncol.2018.356
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: A Novel Patient Case Report to Show the Successful Termination of Untreatable Androgen-independent Prostate Cancer: Treatment with Cabergoline (Dopamine agonist).

    Costello, Leslie C / Franklin, Renty B / Yu, George W

    Mathews journal of case reports

    2019  Band 4, Heft 1

    Abstract: Introduction: Testosterone promotes the initial development of androgen-dependent prostate cancer. This is the basis for androgen ablation treatment, which attenuates, but does not terminate, the malignancy. Instead, it leads to prolactin-dependent ... ...

    Abstract Introduction: Testosterone promotes the initial development of androgen-dependent prostate cancer. This is the basis for androgen ablation treatment, which attenuates, but does not terminate, the malignancy. Instead, it leads to prolactin-dependent malignancy; in which patient death generally occurs within 5 years. This report describes the novel treatment of a patient; which terminated androgen-independent prostate cancer.
    Results: Patient "XY" was diagnosed with prostate malignancy and metastases. He received hormonal androgen ablation treatment, chemotherapy, and radiation treatment. He developed androgen-independent prostate cancer; with expected death in 2-3 years. He was treated with cabergoline (dopamine agonist) treatment, which decreased the plasma prolactin 88%; by inhibiting the pituitary production of prolactin. The subsequent PET scan (positron emission tomography) revealed the absence of malignancy; and the CTC (circulating tumor cells) decreased from count=5.4 to count=0.
    Discussion: The cause of androgen-independent malignancy has been unknown, and an effective chemotherapy did not exist. The activities of normal and malignant prostate cells are regulated primarily by testosterone. When testosterone availability diminishes; prolactin regulation is manifested. This is represented when androgen ablation results in the development of prolactin-dependent malignancy. An effective chemotherapy would be targeted to eliminate the plasma prolactin-manifestation of the androgen-independent malignancy.
    Conclusions: This report of a novel chemotherapy for androgen-independent malignancy corroborates our understanding of the implications of prolactin in its development and treatment. There are about 165,000 cases/year with 25,000 deaths/year in the U.S.; and 1.0 million cases/year with 260,000 deaths/year worldwide. Those patients with androgen-independent prostate cancer can now employ this cabergoline treatment to prevent or terminate this deadly type of prostate cancer.
    Sprache Englisch
    Erscheinungsdatum 2019-05-08
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2474-3666
    ISSN (online) 2474-3666
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Decreased zinc in the development and progression of malignancy: an important common relationship and potential for prevention and treatment of carcinomas.

    Costello, Leslie C / Franklin, Renty B

    Expert opinion on therapeutic targets

    2016  Band 21, Heft 1, Seite(n) 51–66

    Abstract: Introduction: Efficacious chemotherapy does not exist for treatment or prevention of prostate, liver, and pancreatic carcinomas, and some other cancers that exhibit decreased zinc in malignancy. Zinc treatment offers a potential solution; but its ... ...

    Abstract Introduction: Efficacious chemotherapy does not exist for treatment or prevention of prostate, liver, and pancreatic carcinomas, and some other cancers that exhibit decreased zinc in malignancy. Zinc treatment offers a potential solution; but its support has been deterred by adverse bias. Areas covered: 1. The clinical and experimental evidence for the common ZIP transporter/Zn down regulation in these cancers. 2. The evidence for a zinc approach to prevent and/or treat these carcinomas. 3. The issues that introduce bias against support for the zinc approach. Expert opinion: ZIP/Zn downregulation is a clinically established common event in prostate, hepatocellular and pancreatic cancers. 2. Compelling evidence supports the plausibility that a zinc treatment regimen will prevent development of malignancy and termination of progressing malignancy in these cancers; and likely other carcinomas that exhibit decreased zinc. 3. Scientifically-unfounded issues that oppose this ZIP/Zn relationship have introduced bias against support for research and funding of a zinc treatment approach. 4. The clinically-established and supporting experimental evidence provide the scientific credibility that should dictate the support for research and funding of a zinc approach for the treatment and possible prevention of these cancers. 5. This is in the best interest of the medical community and the public-at-large.
    Mesh-Begriff(e) Animals ; Bias ; Disease Progression ; Down-Regulation ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/pathology ; Liver Neoplasms/prevention & control ; Male ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/prevention & control ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/prevention & control ; Repressor Proteins/genetics ; Research Support as Topic ; Zinc/administration & dosage ; Zinc/metabolism
    Chemische Substanzen Repressor Proteins ; ZGPAT protein, human ; Zinc (J41CSQ7QDS)
    Sprache Englisch
    Erscheinungsdatum 2016-12-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2055208-7
    ISSN 1744-7631 ; 1472-8222
    ISSN (online) 1744-7631
    ISSN 1472-8222
    DOI 10.1080/14728222.2017.1265506
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer.

    Costello, Leslie C / Franklin, Renty B

    Archives of biochemistry and biophysics

    2016  Band 611, Seite(n) 100–112

    Abstract: The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, ... ...

    Abstract The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, which is achieved by the high cellular zinc level effects on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued.
    Mesh-Begriff(e) Aconitate Hydratase/metabolism ; Animals ; Biological Transport ; Cation Transport Proteins/metabolism ; Citrates/chemistry ; Disease Progression ; Epithelial Cells/metabolism ; Humans ; Ligands ; Male ; Mitochondria/metabolism ; Prolactin/metabolism ; Prostate/physiology ; Prostatic Neoplasms/metabolism ; Testosterone/metabolism ; Zinc/physiology
    Chemische Substanzen Cation Transport Proteins ; Citrates ; Ligands ; SLC39A1 protein, human ; Testosterone (3XMK78S47O) ; Prolactin (9002-62-4) ; Aconitate Hydratase (EC 4.2.1.3) ; Zinc (J41CSQ7QDS)
    Sprache Englisch
    Erscheinungsdatum 2016-12-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 523-x
    ISSN 1096-0384 ; 0003-9861
    ISSN (online) 1096-0384
    ISSN 0003-9861
    DOI 10.1016/j.abb.2016.04.014
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Plasma Citrate Homeostasis: How It Is Regulated; And Its Physiological and Clinical Implications. An Important, But Neglected, Relationship in Medicine.

    Costello, Leslie C / Franklin, Renty B

    HSOA journal of human endocrinology

    2016  Band 1, Heft 1

    Abstract: The homeostatic maintenance of a normal plasma citrate concentration is an important factor in humans and in animals; and is required for many normal physiological activities. Dysregulation of normal plasma citrate presents pathophysiological ... ...

    Abstract The homeostatic maintenance of a normal plasma citrate concentration is an important factor in humans and in animals; and is required for many normal physiological activities. Dysregulation of normal plasma citrate presents pathophysiological hypocitricemic or hypercitricemic conditions. This can lead to clinical consequences in many areas of medicine; such as impaired blood clotting, altered acid/base status, impaired neuromuscular/cardiac activities, hypocitraturia and stone formation, bone disorders with loss of bone strength and increased fractures, hypocitricemia of surgical stress. These important implications of citrate relationships have been largely ignored by the contemporary clinical and biomedical community; to the extent that it is not even described in most current textbooks and review papers. This review describes the physiological, endocrine, and metabolic relationships in the normal regulation and maintenance of plasma citrate; and presents some important clinical consequences of its dysfunctional maintenance. The importance of bone, kidney and liver activities in the maintenance of normal plasma citrate is described along with the citricemic roles of parathyroid hormone, calcitonin and vitamin D. These factors and relationships are presented as the contemporary understanding of the integrated regulation of plasma citrate as the basis for its clinical importance in medicine. The exclusion of these citrate relationships leads to misunderstanding and misrepresentation of physiological and clinical conditions in many issues in medicine and paramedicine areas. The intent of this review is to revive the interest and support for research to address the many unknown and speculative issues of plasma citrate regulation and its important clinical implications. This is in the best interest of the medical community and the public-at-large.
    Sprache Englisch
    Erscheinungsdatum 2016-12-31
    Erscheinungsland United States
    Dokumenttyp Journal Article
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship.

    Costello, Leslie C / Franklin, Renty B

    Cancer biology & therapy

    2014  Band 15, Heft 4, Seite(n) 353–360

    Abstract: Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby ... ...

    Abstract Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic agents and biomarkers for early detection of HCC. A consistent marked decrease in zinc in HCC tumors compared with normal liver is an established clinical relationship, which occurs in virtually all cases of HCC. However, this relationship has been largely ignored by the contemporary clinical and research community. Consequently, the factors and mechanisms involved in this relationship have not been addressed. Thus, the opportunity and potential for its employment as biomarkers for early identification of malignancy, and for development of a chemotherapeutic approach have been lacking. This presentation includes a review of the literature and the description of important recent and new data, which provide the basis for a concept of the role of zinc in the development of HCC. The basis is presented for characterizing HCC malignancy as ZIP14-deficient tumors, and its requirement to prevent zinc cytotoxic effects on the malignant cells. The potential for an efficacious zinc treatment approach for HCC is described. The involvement of zinc in the predisposition for HCC by chronic liver disease/cirrhosis is presented. Hopefully, this presentation will raise the awareness, interest, and support for the much needed research in the implications of zinc in the development and progression of HCC.
    Mesh-Begriff(e) Animals ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cation Transport Proteins/metabolism ; Humans ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Zinc/metabolism ; Zinc Compounds/therapeutic use
    Chemische Substanzen Antineoplastic Agents ; Biomarkers, Tumor ; Cation Transport Proteins ; SLC39A14 protein, human ; Zinc Compounds ; Zinc (J41CSQ7QDS)
    Sprache Englisch
    Erscheinungsdatum 2014-01-21
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2146305-0
    ISSN 1555-8576 ; 1538-4047
    ISSN (online) 1555-8576
    ISSN 1538-4047
    DOI 10.4161/cbt.27633
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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