Roles of carbonic anhydrases in the alimentary tract

2000 ◽  
pp. 461-474
Author(s):  
Seppo Parkkila
Keyword(s):  
Alimentary Tract ◽  
Carbonic Anhydrases

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

State of the Art on Carbonic Anhydrase Modulators for Biomedical Purposes

2019 ◽  
Vol 26 (15) ◽  
pp. 2558-2573 ◽  
Author(s):  
Murat Bozdag ◽  
Abdulmalik Saleh Alfawaz Altamimi ◽  
Daniela Vullo ◽  
Claudiu T. Supuran ◽  
Fabrizio Carta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
State Of The Art ◽  
Cellular Level ◽  
Hydration Reaction ◽  
Carbonic Anhydrases ◽  
Crucial Importance ◽  
Learning Impairments ◽  
Current Review ◽  
Potential Use

The current review is intended to highlight recent advances in the search of new and effective modulators of the metalloenzymes Carbonic Anhydrases (CAs, EC 4.2.1.1) expressed in humans (h). CAs reversibly catalyze the CO2 hydration reaction, which is of crucial importance in the regulation of a plethora of fundamental processes at cellular level as well as in complex organisms. The first section of this review will be dedicated to compounds acting as activators of the hCAs (CAAs) and their promising effects on central nervous system affecting pathologies mainly characterized from memory and learning impairments. The second part will focus on the emerging chemical classes acting as hCA inhibitors (CAIs) and their potential use for the treatment of diseases.

MOTOR FUNCTIONS OF THE ALIMENTARY TRACT

BMJ ◽  
1938 ◽  
Vol 1 (4020) ◽  
pp. 176-176
Keyword(s):  
Alimentary Tract ◽  
Motor Functions

scholarly journals Angiosarcoma of sigmoid colon with intraperitoneal bleeding: case report and literature review

2011 ◽  
Vol 93 (6) ◽  
pp. e91-e93 ◽  
Author(s):  
Tse-Hua Lo ◽  
Mu-Shiun Tsai ◽  
Tzu-An Chen
Keyword(s):  
Sigmoid Colon ◽  
Alimentary Tract ◽  
Surgical Excision ◽  
Sigmoid Colectomy ◽  
Epithelioid Cells ◽  
Spindle Cells ◽  
Choice Of Treatment ◽  
Intraperitoneal Bleeding ◽  
Immunohistochemical Studies

Primary angiosarcomas arising from the alimentary tract are rare and only a few cases have been reported in the literature. We report a case of an angiosarcoma of the sigmoid colon with intraperitoneal bleeding but not rectal bleeding. A 21-year-old female patient received a laparotomy and a mass lesion over the sigmoid colon was found with active bleeding. A sigmoid colectomy was performed as a curative resection. Grossly, the sigmoid colon contained a kidney shaped, hemorrhagic tumour from the submucosal layer extension to the antimesenteric side. Intraluminally, the mucosa of the colon was intact. Microscopic examination revealed a high grade angiosarcoma composed of fascicles of spindle cells and solid sheets of epithelioid cells. Immunohistochemical stains revealed a positive result for CD31 and the endothelial nature of the malignancy was confirmed. Smooth muscle antigens, desmins, cytokeratins AE1/AE3 and CD117 were all negative. The patient is still alive without evidence of recurrence or metastasis at a three-year follow-up appointment. Owing to the availability of immunohistochemical studies, some atypical sarcomas would now be correctly classified as angiosarcomas. Since no optimal adjuvant treatment is effective, curative surgical excision is still the best choice of treatment.

scholarly journals Society for Surgery of the Alimentary Tract

1966 ◽  
Vol 50 (1) ◽  
pp. 159-165
Author(s):  
Robert Turell
Keyword(s):  
Alimentary Tract
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