Molecular mechanisms of hemostasis impairment in oncology

Malignant neoplasms are characterized by the presence of the hemostasis system pathology, predisposing cancer patients to thrombohemorrhagic complications. The pathogenesis of cancer-associated coagulopathy is complex and involves a variety of mechanisms. Tumor cells have the ability to activate the host’s hemostasis system, and this phenomenon is controlled by the same oncogenes that are responsible for neoplastic transformation. In addition to predisposing factors to impaired hemostasis from the side of the disease, the anticancer drugs themselves carry risks of developing coagulation disorders. The pathophysiological basis of this kind of disorders caused by chemotherapy is associated with damage to the endothelium, imbalance of coagulation and anticoagulant proteins, platelet dysfunction and their deficiency. In this article, the authors set themselves the goal of generalizing and updating the current knowledge of the molecular mechanisms that cause thrombohemorrhagic risk in cancer.

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Cancer and Signaling Pathway Deregulation

Handbook of Research on Computational and Systems Biology ◽

10.4018/978-1-60960-491-2.ch017 ◽

2011 ◽

pp. 369-379

Author(s):

Yingchun Liu

Keyword(s):

Cancer Patients ◽

Tumor Cells ◽

Malignant Tumor ◽

Molecular Mechanisms ◽

Complex Disease ◽

Cancer Therapies ◽

Normal Cells ◽

Genetic Aberrations ◽

Cancer Subtypes ◽

Pathway Deregulation

Cancer is a complex disease that is associated with a variety of genetic aberrations. The diagnosis and treatment of cancer have been difficult because of poor understanding of cancer and lack of effective cancer therapies. Many studies have investigated cancer from different perspectives. It remains unclear what molecular mechanisms have triggered and sustained the transition of normal cells to malignant tumor cells in cancer patients. This chapter gives an introduction to the genetic aberrations associated with cancer and a brief view of the topics key to decode cancer, from identifying clinically relevant cancer subtypes to uncovering the pathways deregulated in particular subtypes of cancer.

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Molecular mechanisms of autophagy and its role in cancer development

Revista de la Facultad de Medicina ◽

10.15446/revfacmed.v64n3.54152 ◽

2016 ◽

Vol 64 (3) ◽

pp. 529

Author(s):

Kathleen Salazar-Ramírez ◽

Jhonny Molinares-Rodríguez ◽

Samir Bolívar-González

Keyword(s):

Cancer Patients ◽

Tumor Cells ◽

Therapeutic Efficacy ◽

Molecular Mechanisms ◽

Evolutionary Process ◽

Cancer Development ◽

Cell Homeostasis ◽

Pathological Conditions ◽

Extracellular Stimuli

Autophagy is an evolutionary process preserved in eukaryotes, which removes harmful components and maintains cell homeostasis in response to a variety of extracellular stimuli. It is involved in both physiological and pathological conditions, including cancer.The role of autophagy in the treatment of cancer is described as a “double-edged sword”, which reflects its involvement in tumor suppression, survival and subsequent proliferation of tumor cells. Recent advances are useful for planning appropriate adjustments to inhibit or promote autophagy in order to obtain therapeutic efficacy in cancer patients. The objectives of this review are to clarify the role of autophagy in cancer and to highlight the need for more research in the field.

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The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

Cancers ◽

10.3390/cancers13184721 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4721

Author(s):

Manuel Linder ◽

Elke Pogge von Strandmann

Keyword(s):

Tumor Cells ◽

Immune Cells ◽

Molecular Mechanisms ◽

Defense Mechanism ◽

Immune Cell ◽

Current Knowledge ◽

Cell Activity ◽

Cross Presentation ◽

Membrane Bound ◽

Molecular Patterns

Extracellular vesicles released by tumor cells (T-EVs) are known to contain danger-associated molecular patterns (DAMPs), which are released in response to cellular stress to alert the immune system to the dangerous cell. Part of this defense mechanism is the heat shock protein 70 (HSP70), and HSP70-positive T-EVs are known to trigger anti-tumor immune responses. Moreover, extracellular HSP70 acts as an immunogen that contributes to the cross-presentation of major histocompatibility complex (MHC) class I molecules. However, the release of DAMPs, including HSP70, may also induce chronic inflammation or suppress immune cell activity, promoting tumor growth. Here, we summarize the current knowledge on soluble, membrane-bound, and EV-associated HSP70 regarding their functions in regulating tumor-associated immune cells in the tumor microenvironment. The molecular mechanisms involved in the translocation of HSP70 to the plasma membrane of tumor cells and its release via exosomes or soluble proteins are summarized. Furthermore, perspectives for immunotherapies aimed to target HSP70 and its receptors for cancer treatment are discussed and presented.

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Basis of PD1/PD-L1 Therapies

Journal of Clinical Medicine ◽

10.3390/jcm8122168 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2168 ◽

Cited By ~ 13

Author(s):

Barbara Seliger

Keyword(s):

Tumor Cells ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Checkpoint Inhibitors ◽

Immune Surveillance ◽

Constitutive Expression ◽

Immune Checkpoints ◽

Altered Expression ◽

Variable Expression ◽

Number Of Patients

It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 results in an activation of self-tolerance pathways in both immune cells as well as tumor cells. Thus, these molecules represent excellent targets for T cell-based immunotherapies. However, the efficacy of therapies using checkpoint inhibitors is variable and only a limited number of patients receive a long-term response, while others develop resistances. Therefore, a better insight into the constitutive expression levels and their control as well as the predictive and prognostic value of PD-1/PD-L1, which are controversially discussed due to the methodological assessment, the dynamic and time-related variable expression of these molecules, is urgently required. In this review, the current knowledge of the PD-L1 and PD-1 genes, their expression in immune and tumor cells, the underlying molecular mechanisms of their regulation and their association with clinical parameters and therapy responses are summarized.

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P1.01-038 Identification and Characterization of Circulating Tumor Cells from Lung Cancer Patients for Selecting Target Anticancer Drugs for Relapse

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.692 ◽

2017 ◽

Vol 12 (11) ◽

pp. S1908

Author(s):

B. Kim

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Anticancer Drugs ◽

Lung Cancer Patients ◽

Identification And Characterization

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Mesophyll conductance: the leaf corridors for photosynthesis

Biochemical Society Transactions ◽

10.1042/bst20190312 ◽

2020 ◽

Vol 48 (2) ◽

pp. 429-439 ◽

Cited By ~ 3

Author(s):

Jorge Gago ◽

Danilo M. Daloso ◽

Marc Carriquí ◽

Miquel Nadal ◽

Melanie Morales ◽

...

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Main Role ◽

Mesophyll Conductance ◽

Future Studies ◽

Cell Structures ◽

Leaf Tissues ◽

Change Framework ◽

Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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