Serum Levels of Leptin in Multiple Myeloma Patients and Its Relation to Angiogenic and Inflammatory Cytokines

Background Leptin, apart from the regulation of food intake, has been implicated in hematopoiesis, the immune response and angiogenesis. Leptin has been found to be decreased in various hematological malignancies. In the present study leptin was measured in multiple myeloma (MM) patients before and after treatment and correlated with other angiogenic molecules and markers of disease activity. Methods Serum leptin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), interleukin-1 beta (IL-1β), beta 2 microglobulin (β2M) and C-reactive protein (CRP) were measured in 62 newly diagnosed MM patients, 22 of whom obtaining disease stabilization after treatment. The same parameters were measured in 20 healthy controls. Disease stage was defined according to the Durie-Salmon criteria. Results Leptin, VEGF, b-FGF, IL-1β, and β2M were significantly higher in newly diagnosed MM patients than in controls (p<0.05). VEGF, b-FGF, IL-1β, β2M, CRP but not leptin increased with advancing stage of disease (p<0.01). All parameters decreased significantly following treatment (p<0.001). Although IL-1β correlated positively with VEGF, β2M, b-FGF and CRP, leptin did not correlate with any of the measured parameters. Conclusion Leptin serum levels do not reflect disease severity in MM. However, there seems to be a decrease in leptin following treatment, which may be associated with an alteration in the metabolic state or the chemokine milieu.

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Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment

Mediators of Inflammation ◽

10.1155/2011/867576 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

K. Sfiridaki ◽

C. A. Pappa ◽

G. Tsirakis ◽

P. Kanellou ◽

M. Kaparou ◽

...

Keyword(s):

Multiple Myeloma ◽

Growth Factor ◽

Serum Levels ◽

Response To Treatment ◽

Disease Stage ◽

Vascular Endothelial ◽

Newly Diagnosed ◽

Plateau Phase ◽

Endothelial Growth Factor ◽

Hepatocyte Growth

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6),β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis.

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The Ratio of Angiopoietin-1 to Angiopoietin-2 Is Reduced and Predicts Independently for Survival in Newly Diagnosed Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.1478.1478 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1478-1478

Author(s):

Meletios A. Dimopoulos ◽

Konstantinos Anargyrou ◽

Eirini Katodritou ◽

Efstathios Kastritis ◽

Anastasia Pouli ◽

...

Keyword(s):

Multiple Myeloma ◽

Growth Factor ◽

Median Survival ◽

Bone Disease ◽

Univariate Analysis ◽

Disease Status ◽

Serum Levels ◽

Newly Diagnosed ◽

Angiopoietin 2 ◽

Angiopoietin 1

Abstract Angiogenesis represents an essential step of disease progression in several hematological malignancies, including multiple myeloma (MM). Angiopoietin-1 (Ang-1) and its natural antagonist angiopoietin-2 (Ang-2), both ligands for the receptor tyrosine kinase Tie-2, are essential cytokines for angiogenesis process. Maturation and stabilization of the vascular wall are critically regulated by Ang-1 binding to Tie-2 receptor, while Ang2- antagonizes Tie-2 binding and induces vessel destabilization, which leads to the angiogenic sprouting. Vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF) are also potent stimulators of both physiological and pathological angiogenesis. The aim of this study was to evaluate the serum levels of the above angiogenesis cytokines and explore possible correlations with clinical data, including survival, in 143 newly diagnosed, untreated, MM patients (75M/68F; median age: 68 years, range: 40–94 years). According to ISS, 49 patients had stage 1, 46 stage 2 and 48 stage 3 disease. Serum levels of Ang-1, Ang-2, VEGF, VEGF-A (the major angiogenesis component of VEGF), angiogenin, and bFGF were evaluated using ELISA methodology (R&D Systems, Minneapolis, MN, USA, for all, except VEGF-A: Diaclone, Bensancon, France). MM patients had increased serum levels of Ang-2 (p<0.0001), angiogenin (p<0.0001), VEGF (p=0.033) and VEGF-A (p=0.010) compared with 25 controls of similar age and gender. Ang-1 levels were not different between patients and controls; thus the ratio of Ang-1/Ang-2 was reduced in MM (p<0.0001). Ang-1/Ang-2 ratio correlated with ISS (p=0.022) and beta2-microglobulin (p=0.03), while angiogenin showed strong correlations with ISS (p<0.0001), bone disease status (p=0.01) and hemoglobin (p=0.01). Interestingly, VEGF levels correlated with both Ang-1 (p<0.0001) and Ang-2 (p<0.0001) as well as with bFGF (p<0.0001) and LDH (p=0.01) serum levels. The median survival of all patients was 47 months and the median follow-up was 20 months. The univariate analysis revealed that ISS stage (p=0.001), serum LDH (p=0.001), serum beta2-microglobulin (p=0.0002), bone disease status (p=0.0007), serum creatinine (p=0.045), and the ratio of Ang-1/Ang-2 predicted for survival. Patients with serum Ang-1/Ang-2 of below or equal to the median value (4.8) had a median survival of 25 months, while patients with Ang-1/Ang-2 values of above the median value of 4.8 had a median survival of 53 months (p=0.0065). The multivariate analysis revealed that only serum LDH (p=0.003), Ang-1/Ang-2 ratio (p=0.005) and bone disease status (p=0.015) could independently predict for survival. These results reveal for the first time in MM patients the correlation of reduced Ang-1/Ang-2 ratio with advanced disease and highlight the role of Ang-1/Ang-2 pathway in the biology of plasma cell growth as reflected by its influence on survival. These observations reveal Ang-1/Ang-2/Tie-2 system as a possible target for the development of novel anti-myeloma agents.

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Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction

Journal of Clinical Medicine ◽

10.3390/jcm9103201 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3201

Author(s):

Evangelos Terpos ◽

Ioannis Ntanasis-Stathopoulos ◽

Gerasimos-Petros Papassotiriou ◽

Efstathios Kastritis ◽

Alexandra Margeli ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Function ◽

Plasminogen Activator ◽

Disease Stage ◽

Newly Diagnosed ◽

Best Response ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Before And After ◽

Plasminogen Activator Receptor

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m2. (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.

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Serum Proinflammatory Mediators at Different Periods of Therapy in Patients With Multiple Myeloma

Mediators of Inflammation ◽

10.1155/mi.2005.171 ◽

2005 ◽

Vol 2005 (3) ◽

pp. 171-174 ◽

Cited By ~ 19

Author(s):

Irfan Kuku ◽

Mehmet Refik Bayraktar ◽

Emin Kaya ◽

Mehmet Ali Erkurt ◽

Nihayet Bayraktar ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cells ◽

Interleukin 1 ◽

Interleukin 2 ◽

Serum Levels ◽

Strong Impact ◽

Healthy Controls ◽

Newly Diagnosed ◽

Proinflammatory Mediators ◽

Clonal Proliferation

Multiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells within the bone marrow. Several cytokines have been demonstrated to be involved in the control of growth, progression, and dissemination of MM. We determined serum levels of interleukin-1β(IL-1β), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α), and C-reactive protein (CRP) in 14 newly diagnosed MM patients. The median age of the patients was63.4±10.8years and all of the patients were stage III (classified according to the Durie-Salmon classification). The same parameters were measured in 15 healthy controls. In addition, we also examined the effects of vincristine-adriamycin-dexamethasone (VAD) therapy on the same parameters and mediators as well as the relationship among the parameters in the same patient groups. The serum concentrations of TNF-α, IL-1β, sIL-2R, IL-6, IL-8, and CRP (18.6±3.7pg/mL,10.1±2.8pg/mL,730±220U/mL,11.4±3.3pg/mL,23.9±8.3pg/mL, and49.9±19.5mg/dL, resp) were significantly higher in newly diagnosed MM patients than in healthy controls (P<.0001). All of the parameters were found to be significantly reduced after chemotherapy. In conclusion, we found that after the VAD therapy, the level of these cytokines which are thought to play an important role in the pathogenesis of MM was significantly suppressed. This is the first study demonstrating strong impact of VAD treatment on circulating mediators of sIL-2R and IL-8 levels parameters.

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Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy

Scientific Reports ◽

10.1038/s41598-021-88780-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Meysam Yousefi ◽

Sara Rajaie ◽

Vahideh Keyvani ◽

Somayeh Bolandi ◽

Malihe Hasanzadeh ◽

...

Keyword(s):

Ovarian Cancer ◽

Adjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Clinical Significance ◽

Therapy Response ◽

Serum Levels ◽

Circulating Tumor Cell ◽

Tumor Stage ◽

Disease Stage ◽

Before And After

AbstractCirculating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).

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PO-03 bFGF, IL-6, TNF-α and VEGF serum levels in newly diagnosed multiple myeloma patients treated with thalidomide, dexamethasone and autologous transplantation

Thrombosis Research ◽

10.1016/s0049-3848(07)70156-1 ◽

2007 ◽

Vol 120 ◽

pp. S145-S146

Author(s):

C. Cellini ◽

V. Tazzari ◽

T. Grafone ◽

M. Conti ◽

C. Baccini ◽

...

Keyword(s):

Multiple Myeloma ◽

Autologous Transplantation ◽

Serum Levels ◽

Newly Diagnosed ◽

Tnf Α

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Impact of Serum Albumin and B2-Microglobulin level on 2-Year Overall Survival among Newly Diagnosed Multiple Myeloma Patients: A retrospective Study

RAS Medical Science ◽

10.51520/2766-5240-5 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Sherian Salama ◽

Rodaina Yousef ◽

Asma Al Olama ◽

Mahmoud Marashi ◽

Hana Salama ◽

...

Keyword(s):

Multiple Myeloma ◽

Serum Albumin ◽

United Arab Emirates ◽

Staging System ◽

Albumin Level ◽

Age At Diagnosis ◽

Newly Diagnosed ◽

International Staging System ◽

Beta 2 ◽

Beta 2 Microglobulin

Background: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Evaluation and initial staging of the disease is made once the diagnosis is confirmed. The recommended staging system is the International Staging System (ISS). Which determines the Myeloma prognosis by 2 factors: beta-2 Microglobulin and Serum albumin. Goal and Objective: The main goal of this study is to assess the effect of Beta-2 microglobulin and Serum albumin on patient’s survival rate with Multiple Myeloma. The secondary objective is to compare the age at diagnosis with other literature. Methodology: The current study was carried out in Hematology Unit, Dubai Hospital, Dubai, Dubai Health Authority (DHA), United Arab Emirates. Chart review was done retrospectively for 49 newly diagnosed patients with Multiple Myeloma diagnosed between the period 2012-2016. Purposive sample was used to those patients who met the inclusion criteria of this study, to be diagnosed and treated in DH. diagnosed and received regular treatment in Dubai Hospital. Results: Medina follow-up of the patients in this study was (12.8) months. The 2-year overall survival rate for patients with Multiple Myeloma (n = 49) was approximately 80%. While, the 2-year OS rate based on Albumin level. Patients with albumin level > 3.5 mg\dl was significantly higher compared to those who had an albumin level <3.5 mg\dl. 100%, 65% respectively, P = 0.033. Moreover, the 2-year OS rate in terms B2MG level. Patients who had a B2MG < 3.5 mg\dl OS was slightly higher compared to those who had (3.5-5.5 and 5.5 mg\dl). OS rate approximately 85 %, 80 % and 75 respectively, P = .737 Conclusion: Multiple myeloma (MM) is a very heterogeneous disease. For this reason, various prognostic factors and staging systems have been developed to predict the disease outcome. International Staging System (ISS) is very useful in determine the survival based on serum β2- microglobulin and serum albumin levels. The age at diagnosis in Dubai hospital, United Arab Emirates is much younger compared to other studies conducted worldwide. The sample used in the study was also highly diverse in terms of culture and nationality. Such diversity is largely typical in Gulf especially in United Arab Emirates. Therefore, this can play important role in age at diagnosis.

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