1,720,985 research outputs found
Brush border inositol transport by intestines of carnivourus and herbivourus teleosts. Am. J. Physiol. 256: G501-G508.
No full textSynergy between low dose metronomic chemotherapy and the pH-centered approach against cancer
No full textLow dose metronomic chemotherapy (MC) is becoming a mainstream treatment for cancer in veterinary medicine. Its mechanism of action is anti-angiogenesis by lowering vascular endothelial growth factor (VEGF) and increasing trombospondin-1 (TSP1). It has also been adopted as a compassionate treatment in very advanced human cancer. However, one of the main limitations of this therapy is its short-term effectiveness: 6 to 12 months, after which resistance develops. pH-centered cancer treatment (pHT) has been proposed as a complementary therapy in cancer, but it has not been adopted or tested as a mainstream protocol, in spite of existing evidence of its advantages and benefits. Many of the factors directly or indirectly involved in MC and anti-angiogenic treatment resistance are appropriately antagonized by pHT. This led to the testing of an association between these two treatments. Preliminary evidence indicates that the association of MC and pHT has the ability to reduce anti-angiogenic treatment limitations and develop synergistic anti-cancer effects. This review will describe each of these treatments and will analyze the fundamentals of their synergy
Resistance to antiangiogenic treatments: A review
No full textAngiogenesis (blood vessel formation) is essential for tissue growth in both normal development and physiology and in some diseases such as inflammation and cancer. Angiogenesis is a hallmark of cancer, however, it took many years to establish its importance. Ever since Judah Folkman’s seminal publications in 1971, that clearly showed cancer angiogenesis-dependence, researchers have been investigating the mechanisms of angiogenesis and how to block them. This search blossomed with the finding of inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathways. These new molecules and monoclonal antibodies showed therapeutic efficacy in both the laboratory and human clinical settings and hopes rose. Unfortunately, the benefits did not reach all the patients and they were short-lived: sooner or later tumors resumed their growth and proliferation and became refractory to further antiangiogenic treatments. Worse, antiangiogenic treatments seemed to increase metastatic risk. The development of treatment resistance is still one of the main causes of failure in cancer therapy. Antiangiogenic treatments are no exception and a deeper knowledge of the mechanisms of resistance is necessary if we intend to delay or eliminate them.Two different mechanisms have been identified: primary or evasive resistance and secondary or adaptive resistance.The existence of these two mechanisms led to the non-mainstream conclusion, now shared by many authors, that there are at least two different angiogenic pathways: one is the canonical VEGF- VEGF receptor (VEGFR) axis and others, which are independent of this axis and not fully known. Primary resistance works exclusively through these independent pathways, while secondary resistance, which initially is VEGF-VEGFR-dependent, switches to the other pathways becoming non-responsive to classical antiangiogenic treatments. For the time being, the clear identification of these other pathways belongs to the realm of hypothesis. However, there is enough experimental evidence supporting their existence. We will discuss this evidence as a central issue in antiangiogenic treatment resistance. Some non-conventional pharmacologic strategies against resistance will also be considered
Basolateral amino acid and glucose transport by the intestine of the teleost Anguilla anguilla. Comp. Biochem. Physiol. 91: 779-788
No full textRole of Stromal Cells in Determining Tumor and Cancer Stem Cell Behaviors and Therapeutic Response
No full textWhile research previously focused extensively on the tumor cells, over the last two decades, the tumor microenvironment (TME) has received increasing attention with a particular emphasis in its role in tumor development, metabolism, progression, and treatment response [...
pH Deregulation as the Eleventh Hallmark of Cancer
No full textpH Deregulation as the Eleventh Hallmark of Cancer presents key concepts about pH deregulation in a concise and straight-forward manner. The book discusses topics such as pH regulation and metabolism, sodium hydrogen exchanger, monocarboxylate transporter, V-ATPase proton pump, carbonic anhydrases, and voltage gated sodium channels. In addition, it covers clinical and therapeutic implications and future perspectives. This is a valuable resource for researchers, oncologists, students and members of the biomedical and medical fields who want to learn more about the role of pH deregulation in cancer treatment. pH deregulation can improve the outcome of classical treatments without adding toxicity to them, and the book shows that treating the pH peculiarities of cancer is simple and can be performed with existing drugs. Based on the classification of tumor malignancy in ten hallmarks, the authors put pH deregulation at the spotlight and separated from metabolic reprogramming due to its impact on all other hallmarks, proposing it as an additional characteristic to evaluate and fight cancer
Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer
Full text linkPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Present-day treatments have not shown real improvements in reducing the high mortality rate and the short survival of the disease. The average survival is less than 5% after 5 years. New innovative treatments are necessary to curtail the situation. The very dense pancreatic cancer stroma is a barrier that impedes the access of chemotherapeutic drugs and at the same time establishes a pro-proliferative symbiosis with the tumor, thus targeting the stroma has been suggested by many authors. No ideal drug or drug combination for this targeting has been found as yet. With this goal in mind, here we have explored a different complementary treatment based on abundant previous publications on repurposed drugs. The cell surface protein CD44 is the main receptor for hyaluronan binding. Many malignant tumors show over-expression/over-activity of both. This is particularly significant in pancreatic cancer. The independent inhibition of hyaluronan-producing cells, hyaluronan synthesis, and/or CD44 expression, has been found to decrease the tumor cell’s proliferation, motility, invasion, and metastatic abilities. Targeting the hyaluronan-CD44 pathway seems to have been bypassed by conventional mainstream oncological practice. There are existing drugs that decrease the activity/expression of hyaluronan and CD44: 4-methylumbelliferone and bromelain respectively. Some drugs inhibit hyaluronan-producing cells such as pirfenidone. The association of these three drugs has never been tested either in the laboratory or in the clinical setting. We present a hypothesis, sustained by hard experimental evidence, suggesting that the simultaneous use of these nontoxic drugs can achieve synergistic or added effects in reducing invasion and metastatic potential, in PDAC. A non-toxic, low-cost scheme for inhibiting this pathway may offer an additional weapon for treating pancreatic cancer
Ezrin phosphorylation and activation of RhoA play a role in the rescue of F508CFTR in CFBE41o- cells by NHERF1
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