Multiple myeloma – Treatments of symptoms In conventional medicine perspective

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
A.4. A.4. Treatments of symptoms
1. Painful vertebral compression
Patients with painful vertebral compression fractures produced by multiple myeloma (MM) often experience reduction in pain after spinal augmentation with kyphoplasty or vertebroplasty. According to the study by The University of Texas MD Anderson Cancer Center, pain reduction after spinal augmentation with vertebroplasty or kyphoplasty was positively associated with reduction in other patient-reported cancer-related symptoms. Future studies of these augmentation procedures should measure multiple symptoms, in addition to pain and functional status(61). Patients of Multiple myeloma with common symptoms of back back may be prescribed by apin reliever or a back brace.
2. Infection
Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. According to the study by The Abbott Northwestern Hospital, Minneapolis, administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma(62).
For parients of Mutliple myeloma with complication of infection, antibiotics may be necessary
3. Renal impairment
Renal impairment is a common complication of multiple myeloma (MM) and is supported in virtually all patients by a tubulointerstitial pathology that results from high serum concentrations of monoclonal free light chains (FLCs). According to the study by the UCL Centre for Nephrology, Royal Free Hospital, The mainstay of therapy is presently the removal of aggravating factors (dehydration, hypercalcaemia, nephrotoxic drugs) and the prompt institution of rapidly acting novel chemotherapy combinations. This approach allows the rescue of kidney function in more than two-thirds of patients. High cut-off haemodialysis dialysers may potentially add clinical benefits and the outcomes of controlled trials are eagerly awaited(63).
But other study indicated that if a patient with cast nephropathy and severe acute kidney injury remains dialysis-dependent, the prognosis is poor. A prompt diagnosis and commencement of effective chemotherapy is a critical determinant of renal recovery. A randomized controlled trial of high cut-off haemodialysis in patients with cast nephropathy, who all receive bortezomib-based chemotherapy, is underway(64).
4. Bone diseases
Bone disease associated with multiple myeloma(MM)is characterized by increased osteoclast activity and suppressed osteoclast function because of some factors produced by myeloma cells, leading to severe osteolytic lesions. According to the study by Tochigi Cancer Center, Tochigi, Japan, good control of MM itself is very important in order to manage bone lesions caused by MM. Bisphosphonate(BP), a potent inhibitor of osteoclast activity and function, should be used as adjunctive therapy for MM bone disease. Recently, the MRC Myeloma IX trial demonstrated improved survival and delayed disease progression with the use of an intravenous BP, zoledronate, in patients with newly diagnosed MM. Its results may lead to an alteration of guidelines for BP treatments of MM(65).
Other study also indicated that of treatment of bone diseases of which intravenous pamidronate and zoledronic acid are equally effective in reducing SREs, whereas zoledronic acid seems to offer survival benefits in symptomatic patients. Caution is needed to avoid adverse events, such as renal impairment and osteonecrosis of the jaw. Novel antiresorptive agents, such as denosumab, have given encouraging results, but further studies are needed before their approval for managing myeloma bone disease. Combination approaches with novel antimyeloma agents, such as bortezomib (which has anabolic effects on bone) with bisphosphonates or with drugs that enhance osteoblast function, such as antidickkopf-1 agents, antisclerostin drugs, or sotatercept, may favorably alter our way of managing myeloma bone disease in the near future(66).
5. Anemia
Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. According to the Department of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, treatment options for anemic myeloma patients include red blood cell (RBC) transfusions and recombinant human erythropoietin (rHuEPO).
5.1. Red blood cell transfusions convey an immediate effect and rapidly increase the patient’s hemoglobin level. Unfortunately, effects of RBC transfusions are only transient and can be associated with several risks, including infections and mild to even life-threatening immunologic reactions.
5.2. rHuEPO is biologically equivalent to the human endogenous hormone EPO, and its application leads to an increase of hemoglobin levels over an extended time without the risks of blood transfusions. Several studies reported a significant improvement of erythropoiesis, reduction in transfusion need, and improved quality of life by using rHuEPO as long-term treatment of myeloma-associated anemia. Recently, an international expert panel recommended the use of rHuEPO for anemic myeloma patients where other possible causes of anemia have been eliminated(67).
1. Painful vertebral compression
Patients with painful vertebral compression fractures produced by multiple myeloma (MM) often experience reduction in pain after spinal augmentation with kyphoplasty or vertebroplasty. According to the study by The University of Texas MD Anderson Cancer Center, pain reduction after spinal augmentation with vertebroplasty or kyphoplasty was positively associated with reduction in other patient-reported cancer-related symptoms. Future studies of these augmentation procedures should measure multiple symptoms, in addition to pain and functional status(61). Patients of Multiple myeloma with common symptoms of back back may be prescribed by apin reliever or a back brace.
2. Infection
Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. According to the study by The Abbott Northwestern Hospital, Minneapolis, administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma(62).
For parients of Mutliple myeloma with complication of infection, antibiotics may be necessary
3. Renal impairment
Renal impairment is a common complication of multiple myeloma (MM) and is supported in virtually all patients by a tubulointerstitial pathology that results from high serum concentrations of monoclonal free light chains (FLCs). According to the study by the UCL Centre for Nephrology, Royal Free Hospital, The mainstay of therapy is presently the removal of aggravating factors (dehydration, hypercalcaemia, nephrotoxic drugs) and the prompt institution of rapidly acting novel chemotherapy combinations. This approach allows the rescue of kidney function in more than two-thirds of patients. High cut-off haemodialysis dialysers may potentially add clinical benefits and the outcomes of controlled trials are eagerly awaited(63).
But other study indicated that if a patient with cast nephropathy and severe acute kidney injury remains dialysis-dependent, the prognosis is poor. A prompt diagnosis and commencement of effective chemotherapy is a critical determinant of renal recovery. A randomized controlled trial of high cut-off haemodialysis in patients with cast nephropathy, who all receive bortezomib-based chemotherapy, is underway(64).
4. Bone diseases
Bone disease associated with multiple myeloma(MM)is characterized by increased osteoclast activity and suppressed osteoclast function because of some factors produced by myeloma cells, leading to severe osteolytic lesions. According to the study by Tochigi Cancer Center, Tochigi, Japan, good control of MM itself is very important in order to manage bone lesions caused by MM. Bisphosphonate(BP), a potent inhibitor of osteoclast activity and function, should be used as adjunctive therapy for MM bone disease. Recently, the MRC Myeloma IX trial demonstrated improved survival and delayed disease progression with the use of an intravenous BP, zoledronate, in patients with newly diagnosed MM. Its results may lead to an alteration of guidelines for BP treatments of MM(65).
Other study also indicated that of treatment of bone diseases of which intravenous pamidronate and zoledronic acid are equally effective in reducing SREs, whereas zoledronic acid seems to offer survival benefits in symptomatic patients. Caution is needed to avoid adverse events, such as renal impairment and osteonecrosis of the jaw. Novel antiresorptive agents, such as denosumab, have given encouraging results, but further studies are needed before their approval for managing myeloma bone disease. Combination approaches with novel antimyeloma agents, such as bortezomib (which has anabolic effects on bone) with bisphosphonates or with drugs that enhance osteoblast function, such as antidickkopf-1 agents, antisclerostin drugs, or sotatercept, may favorably alter our way of managing myeloma bone disease in the near future(66).
5. Anemia
Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. According to the Department of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, treatment options for anemic myeloma patients include red blood cell (RBC) transfusions and recombinant human erythropoietin (rHuEPO).
5.1. Red blood cell transfusions convey an immediate effect and rapidly increase the patient’s hemoglobin level. Unfortunately, effects of RBC transfusions are only transient and can be associated with several risks, including infections and mild to even life-threatening immunologic reactions.
5.2. rHuEPO is biologically equivalent to the human endogenous hormone EPO, and its application leads to an increase of hemoglobin levels over an extended time without the risks of blood transfusions. Several studies reported a significant improvement of erythropoiesis, reduction in transfusion need, and improved quality of life by using rHuEPO as long-term treatment of myeloma-associated anemia. Recently, an international expert panel recommended the use of rHuEPO for anemic myeloma patients where other possible causes of anemia have been eliminated(67).
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(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(61) http://www.ncbi.nlm.nih.gov/pubmed/22543044
(62) http://www.ncbi.nlm.nih.gov/pubmed/8678082.
(63) http://www.ncbi.nlm.nih.gov/pubmed/23114897
(64) http://www.ncbi.nlm.nih.gov/pubmed/20827195
(65) http://www.ncbi.nlm.nih.gov/pubmed/22902442
(66) http://www.ncbi.nlm.nih.gov/pubmed/21483016
(67) http://www.ncbi.nlm.nih.gov/pubmed/16163188

Multiple myeloma – Treatments for relapsed or treatment-resistant multiple myeloma In conventional medicine perspective

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
VI. Treatments
A. In conventional medicine perspective
A.3. Treatments for relapsed or treatment-resistant multiple myeloma
According to the study to estimate the efficacy of thalidomide monotherapy in the treatment of refractory and relapsed cases of multiple myelomaby Katedry i Kliniki Hematologii i Transplantacji Szpiku Kostnego Slaskiej Akademii Medycznej w Katowicach, found that the good tolerance of the drug, especially in lower doses, and lack of myelosuppression effect allows to expect, that the combination of thalidomide with other cytostatic drugs will improve the efficacy in patients with refractory or relapsed myeloma(59).
Other study in an assessment to compare the costs of two recent treatments (bortezomib (BORT) and lenalidomide plus dexamethasone (LEN/DEX)) for relapsed/refractory multiple myeloma (rrMM), from the perspective of a United States (US) payer, found that drug costs for the treatments were very similar, differing by under $10 per day. Medical and AE management costs for BORT were higher by more than $40 per day. Treatment with BORT had annual excess total costs of >$17,000 compared with LEN/DEX. A cost advantage for LEN/DEX was maintained across a variety of sensitivity analyses. Total cost per month without progression was 11% lower with LEN/DEX. rrMM treatment with BORT and LEN/DEX had comparable drug costs, total treatment costs for BORT were higher due to ongoing direct medical and AE management costs. Total costs per outcome (a month without disease progression) were lower for LEN/DEX, according to the study by Cedars-Sinai Samuel Oschin Cancer Center(60).
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(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(59) http://www.ncbi.nlm.nih.gov/pubmed/14526479
(60) http://www.ncbi.nlm.nih.gov/pubmed/23281721

Multiple myeloma – Initial therapy for myeloma treatments In conventional medicine perspective

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
VI. Treatments
A. In conventional medicine perspective
There is no cure for multiple myeloma. The aim of the treatment is to relieve the symptoms and bring back the normal quality of life in the patients.
A.2. Initial therapy for myeloma
Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. The choice of initial therapy is affected by two main factors: risk-stratification and eligibility for autologous hematopoietic cell transplantation (HCT) and it has the potential for cure, but as a cost of increased treatment-related mortality.
The introduction of plerixafor as a peripheral blood stem cell mobilization agent has allowed more patients with multiple myeloma, non-Hodgkin’s lymphoma, and Hodgkin’s disease to mobilize sufficient hematopoietic progenitor cells (HPCs) to proceed to autologous transplantation, according to the study by the Columbia University, University of Pennsylvania,(57).
Hematopoietic stem cell transplantation (HSCT) is an effective therapy for hematological diseases such as lymphoma and multiple myeloma. According to the Unidad de Hematología Intensiva, Hospital del Salvador, 6 patients with Hodgkin lymphoma, three with multiple myeloma and one with a diffuse large B cell lymphoma were transplanted. Age range was 19 to 48 years and five patients were male. An average of 2.2 aphereses per patient was required. The CD 34 stem cell collection was 5.06 x 10(6) x Kg. The conditioning regimes were BEAM (carmus-tine, etoposide, cytosine arabinoside, melphalan) and melphalan 200 according to the underlying disease. Seventy percent of the patients developed mild to moderate mucositis and 50% had febrile neutropenia, with good response to treatment. In two cases there was an association with influenza. The engraftment of neutrophils and platelets was achieved on day +10 and +11 respectively. At follow-up until day +100, there was no morbidity or mortality(58).
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(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(57) http://www.ncbi.nlm.nih.gov/pubmed/23362980
(58) http://www.ncbi.nlm.nih.gov/pubmed/23354645

Multiple myeloma – Standard treatments In conventional medicine perspective

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
VI. Treatments
A. In conventional medicine perspective
There is no cure for multiple myeloma. The aim of the treatment is to relieve the symptoms and bring back the normal quality of life in the patients.
A.1. Standard treatment
Thalidomide (T) and lenalidomide (R) had been used as first line therapy for previously untreated myeloma. In the study to to assess the treatment effects of lenalidomide-versus thalidomide-based regimen via common comparators, found that lenalidomide seemed to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further the direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted(51a). Other study indicated that LBCT is more efficient in the treatment of MM and has significant role in serum protein alterations especially in the reduction of M-protein in the MM patients(51b).
1. Immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib, carfilzomib) and chemotherapy
Immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib, carfilzomib) can induce apoptosis of myeloma plasma cells and suppress cytokine release and metabolic ways which sustain the disease. These novel agents demonstrate substantial activity either alone or as part of a range of combination regimens. MM therapy is now based on 1 or 2 new drugs plus standard chemotherapy, according to Azienda Ospedaliera Careggi(51). Other study indicated that although high-dose therapy with stem cell transplantation (SCT) and novel targeted therapies (thalidomide, its more potent analogues, and bortezomib) represent two approaches for overcoming resistance of multiple myeloma (MM) cells to conventional therapies, Gene expression profiling (GEP) will help to improve the management of MM not only by identifying prognostic subgroups but also by defining molecular pathways that are associated with these subgroups and that are possible targets for future therapies(52).
2. Corticosteroids
Corticosteroids may be used in patients of multiple myeloma with Disorder of glucose metabolism regulation. According to the study by Interní hematoonkologická klinika Lékarské fakulty MU a FN Brno, The deterioration of glucose tolerance leads to worsening of morbidity and mortality of seriously ill patients. In glucocorticoid-induced diabetes mellitus the highest levels of glucose are seen in the afternoon, in the evening and postprandially: Normal levels of glucose are seen in the morning. Excluding 11 patients with diabetes (16%), we idenfied 7 (10%) patients with normal glucose tolerance, 13 (19%) patients with impaired fasting glucose or/and impaired glucose tolerance and glucocorticoid-induced diabetes mellitus we found in 37 (55%) patients treated in our department with diagnosis of myeloma multiplex in the year 2004 intermitently with 40 mg dexamethason(53).
3. Radiation therapy for local symptoms
In the review of the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma of of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990, found that rtherapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients(54).
4. Stem cell transplantation
A high dose of melphalan followed by autologous stem cell transplantation (ASCT) is considered as the standard therapy for multiple myeloma(55).
5. Treatments and Supportive care
Treatment of younger fit patients with Multiple myeloma is with induction therapy consisting of steroids with one or more novel anti-myeloma agents followed by high dose melphalan and autologous stem cell transplantation, while older and less fit patients are treated with melphalan-based combination chemotherapy. Supportive care is of paramount importance and includes the use of bisphosphonates, prophylactic antibiotics, thrombosis prophylaxis and the use of hematopoietic growth factors along with the treatment of complications of disease and its therapy(56).
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Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca   Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(51) http://www.ncbi.nlm.nih.gov/pubmed/23289028
(51a) http://www.ncbi.nlm.nih.gov/pubmed/23394458
(51b) http://www.ncbi.nlm.nih.gov/pubmed/23303000
(52) http://www.ncbi.nlm.nih.gov/pubmed/15561686
(53) http://www.ncbi.nlm.nih.gov/pubmed/17472011
(54) http://www.ncbi.nlm.nih.gov/pubmed/7683017
(55) http://www.ncbi.nlm.nih.gov/pubmed/23391654
(56) http://www.ncbi.nlm.nih.gov/pubmed/23386937

Multiple myeloma – Antioxidants to prevent Multiple myeloma

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
V. Preventions
C. Antioxidants to prevent Multiple myeloma
According to the study by University of Iowa, Iowa Cityprovides, there is stronge evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy(46).
According to the study by the Chinese Academy of Medical Sciences and Peking Union Medical College, 4 antioxidant constituents from black tea, namely theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B) and theaflavin digallate (TF3) have stronger antioxidant activity than that of BHT (Butylated hydorxytoluene)(47).
1. Theaflavin (TF1)
Black tea extract (T5550) enriched in theaflavins inhibited the chymotrypsin-like (CT) activity of the proteasome and proliferation of human multiple myeloma cells in a dose-dependent manner, according to Chinese Academy of Medical Sciences and Peking Union Medical College(48).
2. Vitamin A
Retinoids are vitamin A derivatives that critically regulate several physiological and pathological processes, including immune functions and cancer development. According to the study by the Seràgnoli University of Bologna, in vitro treatment with retinoids decreases bcl-2 protein expression and enhances dexamethasone-induced cytotoxicity and apoptosis in multiple myeloma cells(49).
3. Quercetin and myricetin
Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. This inhibitory effect was associated with chemical reactions between quercetin and the boronic acid group, -RB(OH)2, in bortezomib. The addition of boric acid diminished the inhibitory effect of both quercetin and plasma on bortezomib-induced apoptosis. The protective effect was also reduced when myeloma cell lines, but not B-cell lines, were preincubated with quercetin, indicating a direct effect of quercetin on myeloma cells. At high doses, quercetin itself induced tumor cell death(50).
4. Betulinic acid
According to the study by The University of Texas M. D. Anderson Cancer Center, in the study to investigate Whether betulinic acid, a pentacyclic triterpene, can modulate the STAT3 pathway, was investigated in human multiple myeloma (MM) cells, indicated that betulinic acid inhibited constitutive activation of STAT3, Src kinase, JAK1 and JAK2. Pervanadate reversed the betulinic acid-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase (PTP). Furthermore, betulinic acid induced the expression of the PTP SHP-1 and silencing of the SHP-1 gene abolished the ability of betulinic acid to inhibit STAT3 activation and rescued betulinic acid-induced cell death. Betulinic acid also downregulated the expression of STAT3-regulated gene products such as bcl-xL, bcl-2, cyclin D1 and survivin(50a)
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(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(46) http://www.ncbi.nlm.nih.gov/pubmed/22471522
(47) http://www.ncbi.nlm.nih.gov/pubmed/15850353
(48) http://www.ncbi.nlm.nih.gov/pubmed/?term=theaflavin+and+Multiple+myeloma
(49) http://www.ncbi.nlm.nih.gov/pubmed/10089890
(50) http://www.ncbi.nlm.nih.gov/pubmed/?term=Myricetin+in+multiple+myeloma
(50a) http://www.ncbi.nlm.nih.gov/pubmed/19937797

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All rights reserved. Any reproducing of this article must have the author name and all the links intact. "Let Take Care Your Health, Your Health Will Take Care You" Kyle J. Norton I have been studying natural remedies for disease prevention for over 20 years and working as a financial consultant since 1990. Master degree in Mathematics, teaching and tutoring math at colleges and universities before joining insurance industries. Part time Health, Insurance and Entertainment Article Writer.

Multiple myeloma – Phytochemicals to prevent Multiple myeloma

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
V. Preventions
B. Phytochemicals to prevent Multiple myeloma
1. Curcumin
Curcumin (diferuloylmethane), a yellow pigment in turmeric, has been shown to inhibit the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor closely linked to chemoresistance in multiple myeloma cells. According to the study by The University of Texas M. D. Anderson Cancer Center,, curcumin inhibited the proliferation of human multiple myeloma cells regardless of their sensitivity to dexamethasone, doxorubicin, or melphalan. Curcumin also potentiated the apoptotic effects of thalidomide and bortezomib by down-regulating the constitutive activation of NF-kappaB and Akt, and this correlated with the suppression of NF-kappaB-regulated gene products, including cyclin D1, Bcl-xL, Bcl-2, TRAF1, cIAP-1, XIAP, survivin, and vascular endothelial growth factor(42).
2. Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation.(43).
3. Resveratrol
Resveratrol exerts its chemotherapeutic effect on human MM cells through mechanisms involving the impairment of the pro-survival XBP1 signaling and the activation of pro-apoptotic ER stress response(44).
4. Retinoic acid
All-trans retinoic acid (ATRA) is a derivative of vitamin A. ATRA inhibits the growth of human myeloma cell lines and freshly isolated myeloma cells in vitro mainly by down-regulating interleukin-6 receptor. In the study of patients with stable multiple myeloma after conventional chemotherapy received ATRA alone for 2 months, followed by a combination of ATRA and the chemotherapy regimen, showed that the bone marrow cells of responding patients were sensitive to ATRA in vitro. These results show that ATRA alone is not effective to treat multiple myeloma. There may be some beneficial effect of ATRA in combination chemotherapy in selected patients who have activated IL-6 signalingm, according to Turku University Central Hospital(45).
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(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(42) http://www.ncbi.nlm.nih.gov/pubmed/19372569
(43) http://www.ncbi.nlm.nih.gov/pubmed/16809610
(44) http://www.ncbi.nlm.nih.gov/pubmed/21723843
(45) http://www.ncbi.nlm.nih.gov/pubmed/15160951

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All rights reserved. Any reproducing of this article must have the author name and all the links intact. "Let Take Care Your Health, Your Health Will Take Care You" Kyle J. Norton I have been studying natural remedies for disease prevention for over 20 years and working as a financial consultant since 1990. Master degree in Mathematics, teaching and tutoring math at colleges and universities before joining insurance industries. Part time Health, Insurance and Entertainment Article Writer.

Multiple myeloma- Diet to prevent Multiple myeloma

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a type of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
V. Preventions
A. Diet to prevent Multiple myeloma
1. Turmeric
In the study of Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis, scientists at the The University of Texas MD Anderson Cancer Center, showed that Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5′-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan(38)
2. Green tea
(-)-epigallocatechin-3-gallate extracted from green tea have exerted the inhibitory effect against multiple myeloma cells. Dr. Shammas MA and the research team at Veterans Administration Boston Health Care System, and Dana Farber Cancer Institute/Harvard Medical School, showed that EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18)(39)
3. Skins and seed of grape and wine
In the study to investigate the effect of Resveratrol trans-3, 4′, 5,-trihydroxystilbene, insuppressing the multiple myeloma (MM), found that Resveratrol activated IRE1α as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1α and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter(40)
4. Carrot
Retinoic acid found of a measure amount in carrot has a potential in prevent and treat Myeloma (Multiple Myenoma). Study showed that The inhibitory effect of cRA was significantly superior to tRA (P = 0.0129) and IFN-alpha, similar to IFN-gamma and DEX. The combinations of cRA + IFN alpha, tRA + IFN-gamma, tRA + DEX did not show any synergistic effect on myeloma proliferation. In contrast, the combination cRA + DEX (0.29 +/- 0.04, M +/- SEM) markedly increased the effect of both cRA and DEX used as single agents. Ig synthesis was not significantly affected by CRA, tRA, IFN-gamma and the combination tRA + IFN-gamma. As expected, only IFN-alpha (P = 0.002) and DEX (P < 0.001) inhibited Ig production(41).
5. Black tea
In the study to assess the effect of its polyphenols, theaflavins found in black tea on the tumor's cellular proteasome function, an important biological target in cancer prevention, found that black tea extract (T5550) enriched in theaflavins inhibited the chymotrypsin-like (CT) activity of the proteasome and proliferation of human multiple myeloma cells in a dose-dependent manner(41a).
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(38) http://www.ncbi.nlm.nih.gov/pubmed/12393461
(39) http://www.ncbi.nlm.nih.gov/pubmed/16809610
(40) http://www.ncbi.nlm.nih.gov/pubmed/21723843
(41) http://www.ncbi.nlm.nih.gov/pubmed/7734354
(41a) http://www.ncbi.nlm.nih.gov/pubmed/22351658
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367

About kylenorton

All rights reserved. Any reproducing of this article must have the author name and all the links intact. "Let Take Care Your Health, Your Health Will Take Care You" Kyle J. Norton I have been studying natural remedies for disease prevention for over 20 years and working as a financial consultant since 1990. Master degree in Mathematics, teaching and tutoring math at colleges and universities before joining insurance industries. Part time Health, Insurance and Entertainment Article Writer.