scholarly journals Recent Research on Methods to Improve Tumor Hypoxia Environment

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Xiao-Hua Zhu ◽  
Jun-Xi Du ◽  
Dan Zhu ◽  
Shen-Zhen Ren ◽  
Kun Chen ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Anticancer Drugs ◽  
Disease Burden ◽  
Antitumor Agents ◽  
Tumor Therapy ◽  
Tumor Hypoxia ◽  
Therapeutic Effects ◽  
Chemotherapy Sensitivity ◽  
O2 Supply ◽  
Different Origins

Cancer is a major disease burden worldwide. In recent years, in addition to surgical resection, radiotherapy and chemotherapy are recognized as the most effective methods for treating solid tumors. These methods have been introduced to treat tumors of different origins and stages clinically. However, due to insufficient blood flow and oxygen (O2) supply in solid tumors, hypoxia is caused, leading to decreased sensitivity of tumor cells and poor therapeutic effects. In addition, hypoxia will also lead to resistance to most anticancer drugs, accelerate malignant progress, and increase metastasis. In solid tumors, adequate O2 supply and adequate delivery of anticancer drugs are essential to improve radiotherapy and chemotherapy sensitivity. In recent decades, the researches on relieving tumor hypoxia have attracted researchers’ extensive attention and achieved good results. However, as far as we know, there is no detailed review of the researches on alleviating tumor hypoxia. Therefore, in this contribution, we hope to give an overview of the researches on methods to improve tumor hypoxia environment and summarize their effect and application in tumor therapy, to provide a methodological reference for the research and development of new antitumor agents.

scholarly journals An Easily Expandable Multi-Drug LC-MS Assay for the Simultaneous Quantification of 57 Oral Antitumor Drugs in Human Plasma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6329
Author(s):  
Niklas Kehl ◽  
Katja Schlichtig ◽  
Pauline Dürr ◽  
Laura Bellut ◽  
Frank Dörje ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Antitumor Agents ◽  
Plasma Concentrations ◽  
Antitumor Drugs ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Clinical Routine ◽  
Multiple Tumor ◽  
Simultaneous Quantification ◽  
Exposure Monitoring

Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.

scholarly journals An update on anticancer drug development and delivery targeting carbonic anhydrase IX

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4068 ◽  
Author(s):  
Justina Kazokaitė ◽  
Ashok Aspatwar ◽  
Seppo Parkkila ◽  
Daumantas Matulis
Keyword(s):  
Carbonic Anhydrase ◽  
Solid Tumors ◽  
Antitumor Agents ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Antitumor Drugs ◽  
Enzymatic Assays ◽  
Ca Ix ◽  
Specific Tumor

The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors.

scholarly journals Role of the ABL tyrosine kinases in the epithelial–mesenchymal transition and the metastatic cascade

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jillian Hattaway Luttman ◽  
Ashley Colemon ◽  
Benjamin Mayro ◽  
Ann Marie Pendergast
Keyword(s):  
Solid Tumors ◽  
Tyrosine Kinases ◽  
Epithelial To Mesenchymal Transition ◽  
Kinase Inhibitors ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Metastatic Cascade ◽  
Abl Kinases ◽  
Treatment Paradigm

AbstractThe ABL kinases, ABL1 and ABL2, promote tumor progression and metastasis in various solid tumors. Recent reports have shown that ABL kinases have increased expression and/or activity in solid tumors and that ABL inactivation impairs metastasis. The therapeutic effects of ABL inactivation are due in part to ABL-dependent regulation of diverse cellular processes related to the epithelial to mesenchymal transition and subsequent steps in the metastatic cascade. ABL kinases target multiple signaling pathways required for promoting one or more steps in the metastatic cascade. These findings highlight the potential utility of specific ABL kinase inhibitors as a novel treatment paradigm for patients with advanced metastatic disease.

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Silvani ◽  
M. Caroli ◽  
P. Gaviani ◽  
V. Fetoni ◽  
R. Merli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Solid Tumors ◽  
Antitumor Agents ◽  
Palliative Radiotherapy ◽  
Symptomatic Treatment ◽  
Diagnostic Techniques ◽  
Prospective Clinical Study ◽  
Pattern Of Care ◽  
Bulky Disease

Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

Polymeric micelles for targeted tumor therapy of platinum anticancer drugs

2017 ◽  
Vol 14 (12) ◽  
pp. 1423-1438 ◽  
Author(s):  
Yuki Mochida ◽  
Horacio Cabral ◽  
Kazunori Kataoka
Keyword(s):  
Anticancer Drugs ◽  
Polymeric Micelles ◽  
Tumor Therapy ◽  
Platinum Anticancer Drugs

Abstract 1037: Agents that target the PI3K/mTOR pathway decrease oxygen consumption, reduce tumor hypoxia and improve radiation response in solid tumors.

2013 ◽  
Author(s):  
George J. Cerniglia ◽  
Natalie Daurio ◽  
Shannon M. Gallagher-Colombo ◽  
Theresa M. Busch ◽  
Stephen W. Tuttle ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Solid Tumors ◽  
Tumor Hypoxia ◽  
Mtor Pathway ◽  
Radiation Response

Responsive agarose hydrogel incorporated with natural humic acid and MnO2 nanoparticles for effective relief of tumor hypoxia and enhanced photo-induced tumor therapy

2020 ◽  
Vol 8 (1) ◽  
pp. 353-369 ◽  
Author(s):  
Mengmeng Hou ◽  
Weiwei Liu ◽  
Lei Zhang ◽  
Leiyang Zhang ◽  
Zhigang Xu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Humic Acid ◽  
Tumor Microenvironment ◽  
Tumor Therapy ◽  
Tumor Hypoxia ◽  
Therapeutic Outcome ◽  
Severe Hypoxia ◽  
Tumor Penetration ◽  
Mno2 Nanoparticles ◽  
Agarose Hydrogel

In spite of widespread applications of nano-photosensitizers, poor tumor penetration and severe hypoxia in the tumor microenvironment (TME) always result in an undesirable therapeutic outcome of photodynamic therapy (PDT).

scholarly journals A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 352 ◽  
Author(s):  
Li Liu ◽  
Lu Yan ◽  
Ning Liao ◽  
Wan-Qin Wu ◽  
Jun-Ling Shi
Keyword(s):  
Drug Resistance ◽  
Early Diagnosis ◽  
Successful Treatment ◽  
Therapeutic Target ◽  
Crucial Role ◽  
Tumor Therapy ◽  
Therapeutic Effects ◽  
Cellular Functions ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.

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