Thalidomide multiple myeloma mechanism

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  3. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease
  4. Thalidomide and immunomodulatory drugs (IMiDs) have now been shown to block several pathways important for disease progression in multiple myeloma. First established as agents with antiangiogenic properties, thalidomide and IMiDs inhibit the production of interleukin (IL)-6, which is a growth factor for the proliferation of myeloma cells
  5. Although several mechanisms have been proposed to explain the activity of thalidomide, lenalidomide and pomalidomide in multiple myeloma (MM), including demonstrable anti-angiogenic, anti-proliferative and immunomodulatory effects, the precise cellular targets and molecular mechanisms have only recently become clear

The understanding of the disease's pathophysiology has significantly improved over the past few years, partly due to the discovery of the role of immunomodulatory agents and the study of their mechanism of action. Thalidomide, the first of the immunomodulatory family to be used in the management of multiple myeloma, proved not only to be effective in the treatment of multiple myeloma, but also instigated a wide range of in vitro and in vivo studies to define the pathophysiology of the plasma. Thalomid (thalidomide) for Treatment in Myeloma Thalomid® is an oral immunomodulatory drug, an agent that can modify or regulate the immune system. It has both anti-inflammatory and anti-cancer activities. Thalidomide was first used to treat multiple myeloma in 1997 [Therapeutic effectiveness of thalidomide to multiple myeloma and its mechanism]. [Article in Chinese] Wang M(1), Liu Y, Li Y, Wu H. Author information: (1)Department of Hematology, Dongying Hospital, Dongying 257091, China. OBJECTIVE: To observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM)

BACKGROUND: Thalidomide, as a single agent, has been recently found to induce a clinical response in one third of refractory or relapsed myeloma patients. Although it has been reported that thalidomide significantly inhibits angiogenesis. it is still unclear whether its clinical effect is mediated, at least in part, by its anti-angiogenic properties In 1999, they demonstrated that supporting stromal cells are a significant source of angiogenic molecules in multiple myeloma, suggesting a possible mechanism for its trophism.21'25 In addition to antiangiogenesis, thalidomide has a second mechanism of action that may be relevant in multiple myeloma Thalidomide is used as a first-line treatment in multiple myeloma in combination with dexamethasone or with melphalan and prednisone, to treat acute episodes of erythema nodosum leprosum, and for maintenance therapy. The bacterium that causes tuberculosis (TB) is related to leprosy

Multipelt myelom är en typ av cancer som påverkar en viss typ av vita blodkroppar, så kallade plasmaceller. Dessa celler samlas i benmärg en och delar sig utan kontroll. Det kan skada skelettet och njurarna. Multipelt myelom kan i allmänhet inte botas Although its mechanism of action in myeloma is unclear, several trialsshow that thalidomide is active in 25% to 35% of patients with relapsed myeloma.Since many patients who respond have failed other active regimens, includingtransplantation, these results are impressive

New drugs for treatment of multiple myeloma - The Lancet

Although thalidomide (Thal) was initially used to treat multiple myeloma (MM) because of its known antiangiogenic effects, the mechanism of its anti-MM activity is unclear. These studies demonstrate clinical activity of Thal against MM that is refractory to conventional therapy and delineate mechani The immunomodulatory drug (IMiD) thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Recent advances in the clinical application of these agents and in our understanding of their mechanism of action, and toxicity have made safer and smarter use of these drugs possible Thalidomide may directly inhibit the growth of myeloma cells most likely due to oxidative damage caused by free radicals, which has been implicated as the mechanism of thalidomide‐induced teratogenicity (Parman et al. 1999) More recently, thalidomide has been shown to prevent neoangiogenesis in human malignancies and to exert immunomodulatory and anti-inflammatory properties, although the exact mechanism of action is unclear. 1-5 Thalidomide was first used 10 years ago to treat patients with multiple myeloma (MM)

The proposed mechanisms of action of lenalidomide in mu

tion. Thus, at present, multiple myeloma remains a fatal disease. Pharmacokinetics of thalidomide and mechanism of antimyeloma effect Thalidomide is a racemic mixture of two enantio-isomers. This drug is slowly absorbed in the intestine due to its poor water solubility and is rapidly degraded in plasma with Thalidomide is a more targeted therapy than conventional chemotherapy; however the exact mechanism of action is still not fully understood. There are several theories on how thalidomide works, some or all of which may occur: • It directly kills or suppresses the growth and survival of myeloma cells Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion. Neben K(1), Moehler T, Kraemer A, Benner A, Egerer G, Ho AD, Goldschmidt H. Author information: (1)Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. k.neben@dkfz.d However the introduction of thalidomide has remarkably expanded the therapeutic armamentarium for the management of multiple myeloma. Because of the first encouraging results and the lack of myelosuppressive effect it has been considered ideal for use in combination with chemotherapy and is also being tested in clinical trials of front‐line combination therapy for newly diagnosed patients [ 3 ]

Targeted Therapy in Multiple Myeloma

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Download Citation | [Therapeutic effectiveness of thalidomide to multiple myeloma and its mechanism] | To observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM) Thalidomide (Thd), a potent teratogen, was shown to have therapeutic potential in cancer, primarily in multiple myeloma (MM), yet its mechanism of action has not been elucidated 1. History of multiple myeloma treatment. Multiple myeloma (MM) is a plasma cell malignancy. The World Health Organization ranks MM among immunosecretory peripheral neoplasms of B lymphocytes .MM has complex pathophysiology characterized by accumulation of clonal malignant plasma cells in the bone marrow accompanied by production of monoclonal immunoglobulins or light or heavy chains. In 1998 thalidomide was approved by the U.S. Food and Drug Administration (FDA) for use in newly diagnosed multiple myeloma (MM) under strict regulations. This has led to the development of a number of analogs with fewer side effects and increased potency which include lenalidomide , pomalidomide and apremilast , all of which are currently marketed and manufactured by Celgene

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Thalidomide is being used, in association with dexamethasone 39 and cytotoxic agents such as cyclophosphamide, 40 for the treatment of multiple myeloma. 41 Its mechanism of antitumor action is complex and, besides the inhibition of angiogenesis, also involves induction of apoptosis and other mechanisms. 4 4.. Preclinical activity and mechanism of actionIn vitro studies of thalidomide examining its effect on the myeloma cells as well as the mechanisms of its cytotoxicity has been hampered by several of it properties. First, mechanistic studies with the drug are complicated by its enantiomeric inter-conversion and spontaneous cleavage to many metabolites in solutions at physiologic pH. 25 Second.

Thalidomide for the treatment of multiple myelom

  1. Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis
  2. MD Anderson Has One of the Largest Multidisciplinary Multiple Myeloma Programs in the U.S. Learn More About Our Approach to Multiple Myeloma Diagnosis and Treatment
  3. Singhal and colleagues were the first to describe its effect in the treatment of MM, where it induces apoptosis of myeloma cells, down-regulates expression of adhesion molecules thereby disrupting mutual interactions between myeloma cells and bone marrow stromal cells; thalidomide also possesses anti-angiogenic and anti-inflammatory properties and stimulates host immune cells , , ,
  4. Thalidomide, a sedative hypnotic that had become infamous due to its teratogenic side effects, was first introduced for treating myeloma due to its potential anti-angiogenic activity and became the first effective drug to become available for this disease in over two decades.5, 6 Thalidomide alone or in combination with other drugs rapidly became an important part of the armamentarium for treating myeloma
  5. CONCLUSION: The unbanlace of Th17/Treg cell ratio and abnormality of IL-17, IL-35 levels play an important role in the progression of multiple myeloma. The anti-MM mechanism of thalidomide may relate with the regulation of Th17 / Treg cell ratio and expression levels of IL-17 and IL-35
  6. The mechanism of thrombosis by thalidomide is probably multifactorial and one of them is likely through platelet activation. Further study on the affected pathway/s in the platelet activation process would confirm the exact mechanism of thalidomide-induced thrombosis and potential extended usage of this drug in future. PMID: 2403011

Although thalidomide (Thal) was initially used to treat multiple myeloma (MM) because of its known antiangiogenic effects, the mechanism of its anti-MM activity is unclear. These studies demonstrate clinical activity of Thal against MM that is refractory to conventional therapy and delineate mechanisms of anti-tumor activity of Thal and its potent analogs (immunomodulatory drugs [IMiDs]) thalidomide (MPT) and myeloma Treatments and tests Myeloma Infoguide Series. Myeloma Infoline: 0800 980 3332 or 1800 937 773 from Ireland Myeloma, also known as multiple myeloma, is a type of cancer arising from plasma cells that are normally found in the bone marrow

Velcade®, thalidomide and dexamethasone (VTD) and myeloma Treatments and tests Myeloma Infoguide Series VVTD Infoguide Dec 2016 Final.indd 1TD Infoguide Dec 2016 Final.indd 1 112/01/2017 15:30:522/01/2017 15:30:5 It has been known for more than four decades that patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE). 1 During the past decade, the introduction of the oral immunomodulatory drugs (IMiDs) thalidomide and lenalidomide has improved the clinical outcome of patients diagnosed with MM. 2-3 However, a high rate of thromboembolic complications has been.

Pomalidomide (Pomalyst) is also related to thalidomide and is used to treat multiple myeloma. Some common side effects include low red blood cell counts (anemia) and low white blood cell counts. The risk of nerve damage is not as severe as it is with the other immunomodulating drugs, but it's also linked to an increased risk of blood clots Immunotherapy has attracted increasing attention in the treatment of multiple myeloma due to its advantages of targeting ability and low toxicity level. 2 While there are few studies on the mechanism of immunotherapy resistance, the ability of lenalidomide to regulate the immune function as a second generation of immunomodulators has widely been adopted in the treatment of MM. Elotuzumab (Elo.

Lenalidomide and thalidomide: mechanisms of action

thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multi-ple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs in-hibit release of tumor necrosis factor-α and increas Thalidomide and IMiDs are only able to stimulate T cells that have been partially activated by either anti-CD3 or DC; their presence abrogates the requirement of a secondary co-stimula Both thalidomide-derivatives are successfully used to treat certain bone-marrow cancers such as multiple myeloma. While showing stronger anti-tumor potential, they have fewer side effects than.

The researchers demonstrated that lenalidomide — a more powerful derivative of thalidomide — killed multiple myeloma cells by disabling overactive switches called transcription factors that drive the cells' excessive growth

Molecular mechanism of action of immune-modulatory drugs

We conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering (SMM) or indolent multiple myeloma (IMM). Sixteen patients were studied. Thalidomide was given orally at. Whatever its exact mechanism of action, thalidomide has impressive activity in myeloma, as first reported by Singhal et al (1999 ). In this pivotal study, 84 patients were treated with thalidomide at a starting dose of 200 mg/d, increasing in 200 mg increments every 2 weeks to a maximum dose of 800 mg/d

Thalidomide: present and future in multiple myelom

In this review, we mainly introduce the results of clinical trials using IMiDs in the treatment of multiple myeloma. Thalidomide. In 2008 thalidomide was approved as a treatment for relapsed/refractory multiple myeloma (RRMM) by Pharmaceuticals and Medical Devices Agency (PMDA) in Japan Thalidomide has a number of properties that could explain its activity in myeloma; it can alter the expression of adhesion molecules, 25 suppress the production of tumor necrosis factor α, 26. Microenvironment immune reconstitution patterns correlate with outcomes after autologous transplant in multiple myeloma. (thalidomide, lenalidomide, pomalidomide); NR, no response/disease progression. which is a major mechanism of antitumor efficacy by therapeutic antibodies to tumor antigens,. Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98:1614. Zangari M, Siegel E, Barlogie B, et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002; 100:1168

59 questions with answers in PROTEASOME | Science topic

Thalomid/Thalidomide for Multiple Myeloma The IM

Whilst the mechanism of action of thalidomide remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials both as a single agent and in combination have confirmed benefit in relapsed and refractory disease Thalidomide toxicity also seems to increase when used in conjunction with dexamethasone or other chemotherapy drugs. Of those receiving thalidomide and dexamethasone for multiple myeloma treatment, approximately 10% will discontinue the treatment due to toxicity-related effects

Purpose: This research examines the profile of metabolites of thalidomide that are formed in refractory multiple myeloma patients undergoing thalidomide therapy in comparison with those that are detected in healthy mice. Experimental Design: Urine or plasma samples from patients during thalidomide therapy (100-400 mg daily), or from mice treated i.p. (100 mg/kg) or p.o. with thalidomide (50. We have explored the mechanism of the antiangiogenic effects of thalidomide by structure-activity studies. These investigations revealed that angiogenesis inhibition correlates with teratogenicity but not with tumor necrosis factor-alpha (TFA-alpha) inhibition. Additionally, one analog of thalidomide, 3-aminothalidomide, exhibited an unusual capacity to directly inhibit myeloma cell proliferation

Thalidomide and Its Derivatives: New Promise for Multiple Myeloma Donna Weber, MD Background: The combination of melphalan and prednisone has been accepted as standard treatment for multiple myeloma (MM) because most studies demonstrate only minimal survival benefit of combination chemotherapy regimens when compared with melphalan and prednisone Lenalidomide acts by a novel drug mechanism—modulation of the substrate specificity of the CRL4 CRBN E3 ubiquitin ligase. In multiple myeloma, lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4 CRBN. Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells

[Therapeutic effectiveness of thalidomide to multiple

  1. o-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma
  2. Studies on the mechanism of action of thalidomide revealed the pleiotropic properties of this class of drugs, including their anti-inflammatory, antiangiogenic and immunomodulatory activities
  3. istered to pregnant female. It is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects, even after a single dose. Mortality at or shortly after birth reported in ~40% of infant
  4. Although its mechanism of action in myeloma is unclear, several trials show that thalidomide is active in 25% to 35% of patients with relapsed myeloma. Since many patients who respond have failed other active regimens, including transplantation, these results are impressive
From Anecdote to Targeted Therapy: The Curious Case of

Thalidomide in multiple myeloma, myelodysplastic syndromes

Mechanism of action of thalidomide and 3-aminothalidomide

Learn More About How Multiple Myeloma Is Treated. A Variety of Treatment Options That Depend on Several Factors Thalidomide modulates the biosynthesis of a number of cytokines that are essential to the growth and survival of multiple myeloma cells, suggesting that its primary mechanism of action in multiple myeloma patients involves down-regulation of cytokine synthesis (30, 31) The story of Immunomodulatory drugs for the treatment of multiple myeloma is one of serendipity. The immunomodulatory drug thalidomide was used in the 1950s to treat morning sickness but was discontinued in the early 1960s after it was found to cause birth defects. Dr. Ira Wolmer, a cardiologist had relapsed myeloma Methods: The author reviewed and reports the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents. Results: Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma

Subsequent research showed the diverse mechanism of action of thalidomide including its immunomodulatory effect by inhibition of de novo IgM antibody The pathobiology of multiple myeloma. Thalidomide, which was withdrawn from the European market in late 1961, was re-introduced in April 2008 for treating newly diagnosed multiple myeloma. The drug generated global sales of $132 million in 2017 and $59 million in the first half of 2018. This compares with global sales of $152 million and $70 million in the respective periods Thalidomide is a drug with interesting therapeutic properties but also with severe side effects which require a careful and monitored use. Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma

Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma. Hematol J 2004; 5 : 312-317. CAS Google Schola Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study A 75-year-old woman diagnosed with multiple myeloma in 2007 began treatment with monthly melphalan and prednisone for a total of 9 cycles in combination with thalidomide in 2009. The patient subsequently continued on thalidomide for long-term maintenance therapy. 3 years following initiation of thalidomide, the patient mentioned to her oncologist that her hair had become darker over the years Thalidomide Metabolites in Multiple Myeloma Patients. Seven patients with refractory multiple myeloma, receiving between 100 and 400 mg thalidomide daily, were recruited for this study. Urine samples from patients on thalidomide therapy were analyzed for metabolites using the same procedure as that for murine samples

Thalidomide - Wikipedi

  1. Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated
  2. Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications of leprosy. While it has been used in a number of HIV-associated conditions, such use is associated with increased levels of the virus
  3. Multiple myeloma is a plasma cell proliferative disorder that accounts for 10% of all malignant hematologic neoplasms. In 2002, approximately 14 600 new patients with multiple myeloma will be.
  4. Multiple myeloma is an incurable bone marrow cancer, the treatment of which is notoriously difficult. Only modest advances have been achieved using complex polychemotherapeutic regimens, transplant strategies and supportive therapy. In 1999, when new drugs for myeloma were urgently needed, thalidomide was introduced and opened up a completely new line of therapy for the disease
  5. This paper therefore puts the ability of thalidomide to block the development of new blood vessels as the most likely cause of its side effects. The aim is to produce a compound similar to thalidomide without the side effects, as it is currently an important therapeutic in the treatment of leprosy and multiple myeloma, a form of cancer
  6. The combination of thalidomide-dexamethasone showed superior activity, compared with thalidomide alone, in a study involving 47 patients with resistant multiple myeloma, said Donna M. Weber, MD, assistant professor, Department of Lymphoma and Myeloma, M.D. Anderson Cancer Center
  7. Thalidomide remains one of the world's most notorious drugs due to the severe birth defects it induced in children between 1957 and 1962. Yet, to some this drug is a lifesaver, as it now enjoys renaissance in the treatment for a wide range of conditions including leprosy, multiple myeloma, Behcet's disease, and some cancers

Thalidomide Celgene - FASS Allmänhe

  1. A maintenance treatment with thalidomide at 100 mg a day was safe and seen to delay disease progression by more than three years in multiple myeloma patients with stable disease in a Phase 2 study in Japan, researchers report. Data from the 34-patient trial were published in the International Journal of Hematology in the study, Thalidomide maintenance therapy in Japanese myeloma patients.
  2. Multiple myeloma causes up to 16,000 deaths per year, and 12,000 in the USA.1 For approximately 50 years, the combination of melphalan with prednisone was the reference therapy for elderly patients with multiple myeloma.2,3 Recently, however, the addition of thalidomide or bortezomib or lenalidomide to the standard melphalan plus prednisone combination has changed the treatment paradigm for.
  3. Thalidomide is widely used in the treatment of multiple myeloma (MM). In recent years, several cases of pulmonary hypertension have been reported following treatment with thalidomide. The aim of this review was to evaluate the published literature on multiple myeloma patients with pulmonary hypertension following thalidomide treatment. A literature search was performed between 2000 and 2016
  4. Fingerprint Dive into the research topics of 'Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma'. Together they form a unique fingerprint. pomalidomide Medicine & Life Science
  5. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells
  6. In addition, VEGF may serve as a paracrine growth factor for myeloma cells. Based on the increased angiogenesis observed in myeloma, thalidomide has been studied as antiangiogenic therapy. Although its mechanism of action in myeloma is still unclean thalidomide appears to be active in 25-30% of patients with refractory myeloma
  7. Although researchers have not identified the mechanism by which thalidomide treats multiple myeloma, they suspect several actions are involved, including the possibility that thalidomide suppresses tumor necrosis factor-alpha production, and that it increases the body s production of interleukin-10. Dr

Thalidomide in Multiple Myeloma - Cancer Networ

Thalidomide and its analogs overcome drug resistance of

ToxTutor - Regulation of Consumer Products and Drug SafetyRevlimid (Lenalidomide) for the Treatment of Mantle Cell

Multiple myeloma continues to be an incurable disease. The understanding of the disease's pathophysiology has significantly improved over the past few years, partly due to the discovery of the role of immunomodulatory agents and the study of their mechanism of action. Thalidomide, the first of the immunomodulatory family to be used in the management of multiple myeloma, proved not only to be. In a multicentre study by Palumbo et al, r r r 255 patients with newly diagnosed multiple myeloma were randomised to receive either standard melphalan and prednisolone (MP) or melphalan, prednisolone plus thalidomide (MPT). 126 patients received MP and 129 received MPT at the doses used in this regimen. 50% of the patients enrolled were aged >72 years, with half of these aged >75years Purpose To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). Patients and Methods We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the association of TrPN with 3,404 SNPs. The SNPs were selected in predicted functional regions. Thalomid (thalidomide) by Celgene, in combination with dexamethasone, is a treatment for myeloma, a type of blood cancer.Thalidomide was first marketed in Germany in 1957 and is considered an essential medicine by the World Health Organization.It's available as a generic formulation from multiple companies Novel tubulin-polymerization inhibitor derived from thalidomide directly induces apoptosis in human multiple myeloma cells: Possible anti-myeloma mechanism of thalidomide A 54-year-old woman developed psoriasis on the plantar surface of her feet after 2 weeks of thalidomide 100 mg daily for the treatment of multiple IgG myeloma. She did not have any previous history of psoriasis. Thalidomide was immediately stopped and topical treatment with calcipotriol ointment and β-methasone valerate was started

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