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 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.

Acetazolamide-based [ 18 F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors

2018 ◽  
Vol 28 (5) ◽  
pp. 915-921 ◽  
Author(s):  
Kunal N. More ◽  
Jun Young Lee ◽  
Dong-Yeon Kim ◽  
Nam-Chul Cho ◽  
Ayoung Pyo ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Solid Tumors ◽  
Carbonic Anhydrase Ix ◽  
Ca Ix ◽  
Pet Tracer ◽  
In Vivo Validation

Silicon Substitution for Calcium in the Shell of the Fingernail Clam, Musculium Transversum Studied By X-Ray Analysis

1980 ◽  
Vol 38 ◽  
pp. 560-561
Author(s):  
Judith A. Murphy ◽  
Anthony Paparo ◽  
Richard Sparks
Keyword(s):  
Carbonic Anhydrase ◽  
River Water ◽  
Food Chains ◽  
Well Water ◽  
Shell Formation ◽  
X Ray ◽  
Molluscan Shell ◽  
Fingernail Clams

Fingernail clams (Muscu1ium transversum) are dominant bottom-dwelling animals in some waters of the midwest U.S. These organisms are key links in food chains leading from nutrients in water and mud to fish and ducks which are utilized by man. In the mid-1950’s, fingernail clams disappeared from a 100-mile section of the Illinois R., a tributary of the Mississippi R. Some factor(s) in the river and/or sediment currently prevent clams from recolonizing areas where they were formerly abundant. Recently, clams developed shell deformities and died without reproducing. The greatest mortality and highest incidence of shell deformities appeared in test chambers containing the highest proportion of river water to well water. The molluscan shell consists of CaCO3, and the tissue concerned in its secretion is the mantle. The source of the carbonate is probably from metabolic CO2 and the maintenance of ionized Ca concentration in the mantle is controlled by carbonic anhydrase. The Ca is stored in extracellular concentric spherical granules(0.6-5.5μm) which represent a large amount of inertCa in the mantle. The purpose of this investigation was to examine the role of raw river water and well water on shell formation in the fingernail clam.

Practical consensus recommendations - Current role of immune response evaluation criteria in solid tumors criteria in the management of cancer patients receiving immunotherapy

2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Evaluation Criteria ◽  
Supporting Evidence ◽  
Response Evaluation ◽  
Consensus Recommendation ◽  
Current Role ◽  
New Class ◽  
Response Evaluation Criteria

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

Bridging the Gap of Drug Delivery in Colon Cancer: The Role of Chitosan and Pectin Based Nanocarriers System

2020 ◽  
Vol 17 (10) ◽  
pp. 911-924
Author(s):  
Rohitas Deshmukh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Therapeutic Agent ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Target Tissue ◽  
Polymer Carriers

Colon cancer is one of the most prevalent diseases, and traditional chemotherapy has not been proven beneficial in its treatment. It ranks second in terms of mortality due to all cancers for all ages. Lack of selectivity and poor biodistribution are the biggest challenges in developing potential therapeutic agents for the treatment of colon cancer. Nanoparticles hold enormous prospects as an effective drug delivery system. The delivery systems employing the use of polymers, such as chitosan and pectin as carrier molecules, ensure the maximum absorption of the drug, reduce unwanted side effects and also offer protection to the therapeutic agent from quick clearance or degradation, thus allowing an increased amount of the drug to reach the target tissue or cells. In this systematic review of published literature, the author aimed to assess the role of chitosan and pectin as polymer-carriers in colon targeted delivery of drugs in colon cancer therapy. This review summarizes the various studies employing the use of chitosan and pectin in colon targeted drug delivery systems.

scholarly journals Distinct Expression Patterns of Carbonic Anhydrase IX in Clear Cell, Microcystic, and Angiomatous Meningiomas

2019 ◽  
Vol 78 (12) ◽  
pp. 1081-1088
Author(s):  
Rati Chkheidze ◽  
Patrick J Cimino ◽  
Kimmo J Hatanpaa ◽  
Charles L White ◽  
Manuel Ferreira ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Clear Cell ◽  
Expression Patterns ◽  
Carbonic Anhydrase Ix ◽  
World Health ◽  
Loss Of Function ◽  
Ca Ix ◽  
Hypoxia Marker ◽  
Other World ◽  
Health Organization

Abstract Clear cell, microcytic, and angiomatous meningiomas are 3 vasculature-rich variants with overlapping morphological features but different prognostic and treatment implications. Distinction between them is not always straightforward. We compared the expression patterns of the hypoxia marker carbonic anhydrase IX (CA-IX) in meningiomas with predominant clear cell (n = 15), microcystic (n = 9), or angiomatous (n = 11) morphologies, as well as 117 cases of other World Health Organization recognized histological meningioma variants. Immunostaining for SMARCE1 protein, whose loss-of-function has been associated with clear cell meningiomas, was performed on all clear cell meningiomas, and selected variants of meningiomas as controls. All clear cell meningiomas showed absence of CA-IX expression and loss of nuclear SMARCE1 expression. All microcystic and angiomatous meningiomas showed diffuse CA-IX immunoreactivity and retained nuclear SMARCE1 expression. In other meningioma variants, CA-IX was expressed in a hypoxia-restricted pattern and was highly associated with atypical features such as necrosis, small cell change, and focal clear cell change. In conclusion, CA-IX may serve as a useful diagnostic marker in differentiating clear cell, microcystic, and angiomatous meningiomas.

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

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