Mononuclear cells release low molecular weight factors with anti-cancer activity: A lower level of production by cells of cancer patients.

1998 ◽  
Author(s):  
D Cohen-Aloro ◽  
O Merimsky ◽  
S Bar-Yehuda ◽  
B Klein ◽  
S Kayzer ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Mononuclear Cells ◽  
Low Molecular Weight ◽  
Weight Factors ◽  
Anti Cancer ◽  
Cancer Activity

Anti-cancer properties of low-molecular-weight heparin: Preclinical evidence

2009 ◽  
Vol 102 (08) ◽  
pp. 258-267 ◽  
Author(s):  
Lars Petersen ◽  
Shaker Mousa
Keyword(s):  
Molecular Weight ◽  
Clinical Trials ◽  
Unfractionated Heparin ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumour Progression ◽  
Coagulation Cascade ◽  
Low Molecular Weight ◽  
Anti Cancer ◽  
The Impact

SummaryMalignant conditions are frequently associated with a hypercoaguable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy or radiotherapy on the coagulation cascade. Heparin and, its pharmacokinetically improved versions, low-molecular-weight heparins (LMWH) are effective in the prevention and treatment of thromboembolic events in cancer patients. There are several lines of preclinical evidence suggesting potential benefits of LMWH in hypercoagulation and thrombosis as well as in various processes involved in tumour growth and metastasis.Tinzaparin is a LMWH produced by controlled enzymatic depolymerisation of unfractionated heparin. The efficacy of tinzaparin has been documented in several clinical trials across various conditions and in special patient populations.The main objective of this review is to present the existing knowledge on the preclinical anti-cancer properties of tinzaparin and other LMWH.The evidence for tinzaparin, as well as other LMWH, regarding interference with cancer-induced hypercoagulation, cancer cell proliferation, degradation of extra-cellular matrix, angiogenesis, selectin-mediated binding of platelet and cancer cells, chemokine signalling, tumour progression, and metastasis are reviewed. Certain clinical trials suggest improved survival of cancer patients with deep venous thrombosis treated with LMWH versus unfractionated heparin and when added to the promising preclinical anti-cancer properties of LMWH this warrants further investigations in prospective, randomised, controlled clinical trials in cancer patients.The benefits of LMWH in cancer might at least in part, be independent from its anti-coagulant activities, but may still be partially dependent on its anti-coagulant activities.

scholarly journals Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review

2021 ◽  
Vol 27 ◽  
pp. 107602962097959
Author(s):  
I. A. Vathiotis ◽  
N. K. Syrigos ◽  
E. P. Dimakakos
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Special Populations ◽  
Low Molecular Weight ◽  
Patients With Cancer

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

scholarly journals In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa

Molecules ◽  
2016 ◽  
Vol 21 (5) ◽  
pp. 625 ◽  
Author(s):  
Xiaoxiao Liu ◽  
Yong Liu ◽  
Jiejie Hao ◽  
Xiaoliang Zhao ◽  
Yinzhi Lang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Chondroitin Sulfate ◽  
Sea Cucumber ◽  
Low Molecular Weight ◽  
Anti Cancer ◽  
Cucumaria Frondosa

scholarly journals Molecular Cloning, Expression, and Immunogenicity of MTB12, a Novel Low-Molecular-Weight Antigen Secreted byMycobacterium tuberculosis

1998 ◽  
Vol 66 (9) ◽  
pp. 4208-4214 ◽  
Author(s):  
John R. Webb ◽  
Thomas S. Vedvick ◽  
Mark R. Alderson ◽  
Jeffrey A. Guderian ◽  
Shyian S. Jen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Molecular Cloning ◽  
Mononuclear Cells ◽  
Single Copy ◽  
Low Molecular Weight ◽  
Peripheral Blood Mononuclear ◽  
Purified Protein Derivative ◽  
Culture Filtrate Proteins ◽  
Processed Form

ABSTRACT Proteins secreted into the culture medium by Mycobacterium tuberculosis are thought to play an important role in the development of protective immune responses. In this report, we describe the molecular cloning of a novel, low-molecular-weight antigen (MTB12) secreted by M. tuberculosis. Sequence analysis of the MTB12 gene indicates that the protein is initially synthesized as a 16.6-kDa precursor protein containing a 48-amino-acid hydrophobic leader sequence. The mature, fully processed form of MTB12 protein found in culture filtrates has a molecular mass of 12.5 kDa. MTB12 protein constitutes a major component of the M. tuberculosis culture supernatant and appears to be at least as abundant as several other well-characterized culture filtrate proteins, including members of the 85B complex. MTB12 is encoded by a single-copy gene which is present in both virulent and avirulent strains of the M. tuberculosis complex, the BCG strain of M. bovis, and M. leprae. Recombinant MTB12 containing an N-terminal six-histidine tag was expressed in Escherichia coli and purified by affinity chromatography. Recombinant MTB12 protein elicited in vitro proliferative responses from the peripheral blood mononuclear cells of a number of purified protein derivative-positive (PPD+) human donors but not from PPD− donors.

scholarly journals The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer

2020 ◽  
Author(s):  
Ming-Fang Wu ◽  
Chih-An Lin ◽  
Tzu-Hang Yuan ◽  
Hsiang-Yuan Yeh ◽  
Sheng-Fang Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Malignant Pleural Effusion ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Anti Cancer ◽  
Cancer Activity

Abstract Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. Conclusions We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

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