scholarly journals Mechanisms of the Antitumor Activity of Low Molecular Weight Heparins in Pancreatic Adenocarcinomas

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 432 ◽  
Author(s):  
Alexandros Bokas ◽  
Pavlos Papakotoulas ◽  
Panagiotis Sarantis ◽  
Adriana Papadimitropoulou ◽  
Athanasios G Papavassiliou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Weight ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Resistance Mechanisms ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Treatment And Prevention

Immune checkpoint inhibitors have revolutionized cancer treatment in the last decade. Despite the progress in immunotherapy, most pancreatic cancer patients still do not derive benefit when receiving immune-based therapies. Recently, resistance mechanisms to immune therapies have been mainly focused on tumor microenvironment properties. Pancreatic cancer is considered one of the most lethal and difficult to treat tumors due to its highly immunosuppressive and desmoplastic microenvironment. Low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thromboembolic disease in these patients. However, many nonanticoagulant properties attributed to LMWHs have been described. Exploiting LMWH properties in a combined treatment modality with immune checkpoint inhibition and chemotherapy could provide a new approach in the management of pancreatic adenocarcinoma patients. The ability of LMWH to interfere with various aspects of the tumor microenvironment could result in both the alleviation of immunosuppression and improvement in drug delivery within the tumor, leading to higher cancer cell destruction rates and more potent immune system activity that would, ultimately, lead to better patient outcomes.

Potential alteration of tumor microenvironments by β-mercaptoethanol

2020 ◽  
Author(s):  
Robert E Click
Keyword(s):  
Molecular Weight ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Suppressor Cells ◽  
Low Molecular Weight ◽  
Uptake Inhibition ◽  
Tumor Microenvironments

The therapeutic effectiveness of immune checkpoint inhibitors in cancer patients is quite profound. However, it is generally accepted that further progress is curtailed by accompanying adverse events and by low cure rates linked to the tumor microenvironment. The multitudes of immune processes altered by low-molecular-weight thiols published over the past decades suggest they have potential to alter tumor microenvironment processes which could result in an increase in immune checkpoint inhibitor survival rates. Based on one of the most studied and most potent low-molecular-weight thiols, β-mercaptoethanol (BME), it is proposed that clinical assessment be undertaken to identify any BME benefits with relevance for proliferation/differentiation of immune cells, lymphocyte exhaustion, immunogenicity of tumor antigens and inactivation of suppressor cells/factors. The BME alterations projected to be most effective are: maintenance/replacement of glutathione in lymphocytes via facilitation of cysteine uptake, inhibition of suppressor cells/soluble factors and inactivation of free-radical, reactive oxygen species.

scholarly journals Advisory Board conclusion following the discussion "Controversial issues of low molecular weight heparins use in obstetrics"

2021 ◽  
Vol 15 (4) ◽  
pp. 461-469
Author(s):  
Article Editorial
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Controversial Issues ◽  
Systemic Embolism ◽  
Low Molecular Weight Heparins ◽  
Maternal Complications ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Low Incidence ◽  
Valve Prostheses

Antithrombotic therapy is often used during pregnancy for the treatment and prevention of venous thromboembolism, systemic embolism in patients with heart valve prostheses, for prevention of foetal loss in patients with antiphospholipid syndrome, placenta-mediated complications. In common, low molecular weight heparins (LMWHs) have largely replaced unfractionated heparin as the anticoagulant. However, in case of placenta-mediated complications it has off-label status. The effectiveness and safety of the LMWHs in pregnant women at an increased risk of placenta-mediated complications is discussed in this review. LMWH is effective, safety, easy to administer and associated with a low incidence of foetal and maternal complications.

scholarly journals Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hong-Bo Li ◽  
Zi-Han Yang ◽  
Qing-Qu Guo
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Immune Effector ◽  
Effector Cells ◽  
Pathological Subtype

AbstractPancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting.

scholarly journals Fatal Retroperitoneal Hematoma in a Patient Receiving Enoxaparin for Bilateral Pulmonary Emboli

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Jordan Sexe ◽  
Robin McCarthy ◽  
Navid Dara ◽  
Lyon Brown ◽  
Gaurav Dutta
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Retroperitoneal Hematoma ◽  
Morbidity And Mortality ◽  
Low Molecular Weight ◽  
Pulmonary Emboli ◽  
Low Molecular Weight Heparins ◽  
Vein Thrombosis ◽  
Treatment And Prevention ◽  
Rare Side Effect

Venous thromboembolism occurs when a deep vein thrombosis travels to the lungs and forms a pulmonary embolism. Low-molecular-weight heparins are a mainstay in the treatment and prevention of venous thromboembolism and should be initiated promptly due to substantial morbidity and mortality. A rare side effect of low-molecular-weight heparins is major bleeding, which also carries a significant morbidity and mortality rate. Here, we present a case of a fatal retroperitoneal hematoma in a patient being treated with enoxaparin for bilateral pulmonary emboli.

A Perspective on Low Molecular Weight Heparins in the Management of Thrombosis

1993 ◽  
Vol 13 (S 01) ◽  
pp. S5-S11 ◽  
Author(s):  
Debra Hoppensteadt ◽  
Jeanine Walenga ◽  
A Ahsan ◽  
O Iqbal ◽  
W Jeske ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Mechanism Of Action ◽  
Manufacturing Process ◽  
Laboratory Tests ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Pharmacological Management

SummaryThe introduction of low molecular weight heparins has added a new dimension to the pharmacological management of thrombotic disorders. Because of different chemical and pharmacological characteristics, due to the manufacturing process, each LMWH should be considered as a distinct entitity and only be used for its given indication. A list of commercially available LMWHs is included. The mechanism of action of the LMWHs and their use in various disorders are discussed. Available laboratory tests for monitoring LMWHs are presented and their limitations pointed out.

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