scholarly journals Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors

2019 ◽  
Vol 20 (21) ◽  
pp. 5284 ◽  
Author(s):  
Maxim Shevtsov ◽  
Gabriele Multhoff ◽  
Elena Mikhaylova ◽  
Atsushi Shibata ◽  
Irina Guzhova ◽  
...  
Keyword(s):  
Heat Shock ◽  
Tumor Cell ◽  
Stress Factors ◽  
Cell Physiology ◽  
Cancer Therapies ◽  
Therapeutic Approaches ◽  
Pharmacological Stress ◽  
Proteotoxic Stress ◽  
Optimal Drug ◽  
Anti Cancer

Most molecular chaperones belonging to heat shock protein (HSP) families are known to protect cancer cells from pathologic, environmental and pharmacological stress factors and thereby can hamper anti-cancer therapies. In this review, we present data on inhibitors of the heat shock response (particularly mediated by the chaperones HSP90, HSP70, and HSP27) either as a single treatment or in combination with currently available anti-cancer therapeutic approaches. An overview of the current literature reveals that the co-administration of chaperone inhibitors and targeting drugs results in proteotoxic stress and violates the tumor cell physiology. An optimal drug combination should simultaneously target cytoprotective mechanisms and trigger the imbalance of the tumor cell physiology.

Hypoxia inhibition of camptothecin-induced apoptosis by Bax loss

Biologia ◽  
2012 ◽  
Vol 67 (3) ◽  
Author(s):  
Kyoungsook Park ◽  
Abdela Woubit ◽  
Cesar Fermin ◽  
Gopal Reddy ◽  
Tsegaye Habtemariam ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cancer Therapies ◽  
Normoxic Condition ◽  
Protein Levels ◽  
Cancer Chemotherapeutics ◽  
Apoptotic Protein ◽  
Anti Cancer ◽  
Cell Hypoxia ◽  
Human Solid Tumors ◽  
Induced Apoptosis

AbstractTumor cell hypoxia is linked to the resistance of human solid tumors to the various anti-cancer therapies: thus, its exploitation has been considered to be a potential target for cancer treatment. Previously, we demonstrated for the first time that hypoxia inhibits apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) through blocking translocation of Bax, a pro-apoptotic protein, from the cytosol to the mitochondria. Nevertheless, the molecular mechanism coupling hypoxia to resistance for drugs, especially for anti-cancer chemotherapeutics, still remains to be elucidated. Here, we demonstrate that hypoxia attenuates camptothecin (CPT)-induced apoptosis by decreasing the protein levels of Bax, thereby leading to resistance to the drug. DNA damage after exposure to CPT resulted in an increase of p53, and a concomitant up-regulation of p21, regardless of oxygen content. Under normoxic condition, CPT induced expression of p53 and its down-stream target molecule Bax as well, in the presence of increased p21. In contrast, when preexposed to hypoxia, Bax-inducing activity of CPT was completely lost and the Bax level was even decreased, although CPT increased both p53 and p21 as observed under normoxic condition. Our data indicate that hypoxia attenuates apoptosis via Bax. Our data also suggest that hypoxia regulates tumor cell apoptosis differentially, through regulating Bax translocation or through down-regulating Bax levels, depending on death-inducing signals as shown by TRAIL- or CPT-induced apoptosis.

scholarly journals Doxorubicin hydrochloride liposome and albumin-bound paclitaxel in cancer: a nanotechnology perspective

2021 ◽  
pp. 59-65
Author(s):  
Rajib Hossain ◽  
Rasel Ahmed Khan ◽  
Muhammad Torequl Islam ◽  
Divya Jain ◽  
Pracheta Janmeda ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Active Sites ◽  
Biosynthetic Pathway ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Tumor Cell Membrane ◽  
Routes Of Administration ◽  
Anti Cancer ◽  
Specific Reactions ◽  
Cancerous Cells

Nanoparticles (1-100 nanometres in size), products of nanotechnology, offer a modern way to transport anti-cancer drugs by acting as transporters of drugs into tumor cells, hence quenching tumor cell proliferation. Such nanoparticles may be formulated to bind to the tumor cell membrane or inhibit specific reactions of tumor biosynthetic pathway by gene repression, or directly bind to the active sites of essential enzymes in the biosynthetic pathway. Consequently, drugs are completely delivered to the desired cancerous cells without system interference. Liposomal doxorubicin and albumin-bound paclitaxel are two examples of nanotechnologically developed drugs for treating cancer. Modern knowledge of nanotechnology opens up new opportunities for innovative research on cancer therapies and administration and helps minimize harm to healthy cells. This review focuses on the doses and routes of administration of these chemotherapeutic agents used in treating cancers.

Anti-Cancer Therapeutic Approaches Based on Intracellular and Extracellular Heat Shock Proteins

2007 ◽  
Vol 14 (27) ◽  
pp. 2839-2847 ◽  
Author(s):  
Celine Didelot ◽  
David Lanneau ◽  
Mathilde Brunet ◽  
Anne-Laure Joly ◽  
Aurelie Thonel ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Therapeutic Approaches ◽  
Anti Cancer ◽  
Shock Proteins

ANTICANCER EFFECT OF UVARIA GENUS

2014 ◽  
pp. 98-101
Author(s):  
Thi Bich Hien Le ◽  
Viet Duc Ho ◽  
Thi Hoai Nguyen
Keyword(s):  
Biological Activities ◽  
Current Trend ◽  
Healthcare Systems ◽  
Chemical Compositions ◽  
Cancer Therapies ◽  
Pharmacological Effects ◽  
Anticancer Effect ◽  
Anti Cancer ◽  
Tropical Areas ◽  
Cancer Activity

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

Kinase Inhibitors Targeting Anti-angiogenesis as Anti-cancer Therapies

2012 ◽  
Vol 1 (4) ◽  
pp. 335-346 ◽  
Author(s):  
Jing Liu ◽  
Feiyang Liu ◽  
David L. Waller ◽  
Junfeng Wang ◽  
Qingsong Liu
Keyword(s):  
Kinase Inhibitors ◽  
Cancer Therapies ◽  
Anti Cancer

scholarly journals AB0080 A SYSTEM-LEVEL APPROACH IDENTIFIES A CRITICAL REGULATOR OF CHONDROSARCOMA PROGRESSION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1340.3-1340
Author(s):  
H. Kim ◽  
Y. Cho ◽  
J. H. Kim
Keyword(s):  
Histological Grade ◽  
System Level ◽  
Clinical Approach ◽  
Cancer Therapies ◽  
Functional Roles ◽  
Network Analyses ◽  
Molecular Events ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis ◽  
Chemotherapy Agents

Background:Chondrosarcomas are cartilaginous tumors that constitute one-third of skeletal system cancers. Chondrosarcomas are capable of transitioning to highly metastatic and treatment-refractory states, resulting in significant patient mortality. However, the molecular events accompanying this behavior remain unknown.Objectives:We aimed to uncover the molecular pathway underlying such tumor progression that confers a higher malignancy to chondrosarcoma.Methods:We conducted unsupervised gene co-expression network analyses using transcriptomes of patients with chondrosarcoma and extracted a characteristic transcription network underlying chondrosarcoma malignancy. By implementing a system-level upstream analysis of this gene network, we identified the transcriptional factor as a key regulator governing chondrosarcoma progression. We unraveled the functional roles of the identified factor in promoting tumor growth and metastasis of chondrosarcomas in the context of their unique microenvironments.Results:By conducting system-level upstream analysis, we identified a factor as a transcriptional regulator that governs the malignancy gene module. The identified factor was upregulated in chondrosarcoma biopsies associated with a high histological grade and conferred chondrosarcoma cells invasiveness and tumor-initiating capacity. In an orthotopic xenograft mouse model, the identified factor modulated local outgrowth and pulmonary metastasis of chondrosarcoma. Pharmacological inhibition of the identified factor in conjunction with the chemotherapy agents such as cisplatin or doxorubicin synergistically enhanced chondrosarcoma cell apoptosis and abolished malignant phenotypes of chondrosarcoma in mice.Conclusion:Our study provides a proof of concept evidence that inhibiting the identified factor suppresses progression of chondrosarcoma and improves the efficacy of chemotherapy in cellular and pre-clinical levels. Taken together, we believe that our findings provide novel molecular insights for the development of new anti-cancer therapies to target chondrosarcomas.References:[1]Gelderblom H, et al. The clinical approach towards chondrosarcoma. Oncologist 13, 320-329 (2008)Disclosure of Interests:None declared

scholarly journals A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 174-193
Author(s):  
Jenny Valentina Garmendia ◽  
Juan Bautista De Sanctis
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Inflammatory Cells ◽  
Cell Physiology ◽  
Therapeutic Approaches ◽  
Pharmacological Modulation ◽  
New Therapeutic Approaches ◽  
Pharmacologic Modulation ◽  
Inflammatory Burden

NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

Sign in / Sign up

Export Citation Format

Share Document