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Lactate AND Cancer AND Bicarbonate

Johannes C van der Mijn, Mathijs J Kuiper, Carl E H Siegert, Annabeth E Wassenaar, Carel J M van Noesel, Aernout C Ogilvie
Lactic acidosis is a commonly observed clinical condition that is associated with a poor prognosis, especially in malignancies. We describe a case of an 81-year-old patient who presented with symptoms of tachypnea and general discomfort. Arterial blood gas analysis showed a high anion gap acidosis with a lactate level of 9.5 mmol/L with respiratory compensation. CT scanning showed no signs of pulmonary embolism or other causes of impaired tissue oxygenation. Despite treatment with sodium bicarbonate, the patient developed an adrenalin-resistant cardiac arrest, most likely caused by the acidosis...
September 2017: Case Reports in Oncology
Ayano Kondo, Tsuyoshi Osawa
Conditions of the tumor microenvironment, such as hypoxia or nutrient starvation, play critical roles in cancer progression and malignancy. However, the role of acidic extracellular pH in tumor aggressiveness and its underlying mechanism has not been extensively studied compared to hypoxic or nutrient starvation conditions. In addition, a well-defined culture method to mimic the acidic extracellular tumor microenvironment has not been fully reported. Here we present a simple in vitro culture method to maintain acidic extracellular pH using reduced bicarbonate and increased lactate or HCl concentrations in the culture medium...
November 19, 2017: Journal of Visualized Experiments: JoVE
Hsiao-Ling Cheng, Wen-Tsan Chang, Yu-Chen Hu, Bau-Shan Hsieh, Tzu-Ching Huang, Inn-Wen Chong, Li-Wen Huang, Kee-Lung Chang
Background: Cancer cells proliferate rapidly and are resistant to cell death, relying on aggravated glycolysis to satisfy their increased demand for energy and biosynthetic precursors. However, this process may create unfavorable microenvironments, such as increased acidity, leading to cytotoxicity. Our previous study demonstrated that arecoline induces anoikis of HA22T/VGH hepatoma cells. The present study aimed to examine if arecoline induced anoikis is related to the glycolytic pathway and explore the underlying mechanisms...
2017: Journal of Cancer
Chin F Ng, Hermann B Frieboes
We present a three-dimensional nonlinear tumor growth model composed of heterogeneous cell types in a multicomponent-multispecies system, including viable, dead, healthy host, and extra-cellular matrix (ECM) tissue species. The model includes the capability for abnormal ECM dynamics noted in tumor development, as exemplified by pancreatic ductal adenocarcinoma, including dense desmoplasia typically characterized by a significant increase of interstitial connective tissue. An elastic energy is implemented to provide elasticity to the connective tissue...
October 7, 2017: Journal of Theoretical Biology
Karima Farhat, Caroline E Douma, E Ferrantelli, Pieter M Ter Wee, Robert H J Beelen, Frans J van Ittersum
♦ BACKGROUND: The use of pH-neutral peritoneal dialysis (PD) fluids low in glucose degradation products (GDP) may better preserve the peritoneal membrane and have fewer systemic effects. The effects of conversion from conventional to neutral-pH, low-GDP PD fluids in prevalent patients are unclear. Few studies on the role of neutral-pH, low-GDP PD have studied residual renal function, ultrafiltration, peritonitis incidence and technique failure, transport characteristics, and local and systemic markers of inflammation in prevalent PD patients...
May 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Ranjit Nair, Usman Shah
Lactic acidosis is a potentially life-threatening complication characterized by accumulation of blood lactate resulting in low arterial pH. The majority of lactic acidosis in malignancies are reported in association with hematologic malignancies. It may result from an imbalance between lactate production and hepatic lactate utilization, but the exact pathophysiology is far more complex than what we can fathom from current micromolecular studies. We report a case of a 71-year-old male with metastatic lung cancer presenting with fatal lactic acidosis in the absence of liver involvement...
April 2017: American Journal of the Medical Sciences
Erik R Swenson
Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many responses to hypoxia at both non-genomic and genomic levels, in part via altered hypoxia-inducible factor (HIF) metabolism. Healthy people at high altitude and persons hyperventilating to non-hypoxic stimuli can become alkalotic and alkalemic with arterial pH acutely rising as high as 7.7. Hypoxia-mediated respiratory alkalosis reduces sympathetic tone, blunts hypoxic pulmonary vasoconstriction and hypoxic cerebral vasodilation, and increases hemoglobin oxygen affinity...
2016: Advances in Experimental Medicine and Biology
Taro Hoshino, Hiroki Ishii, Taisuke Kitano, Mitsutoshi Shindo, Haruhisa Miyazawa, Hodaka Yamada, Kiyonori Ito, Yuichiro Ueda, Yoshio Kaku, Keiji Hirai, Honami Mori, Susumu Ookawara, Kaoru Tabei, Yoshiyuki Morishita
BACKGROUND: The highly concentrated lactate in peritoneal dialysis fluid (PDF) has been considered to contribute to peritoneal failure in patients undergoing PD. A new PDF containing a lower lactate concentration, physiological bicarbonate concentration, and neutral pH (bicarbonate/lactate-buffered neutral PDF) was recently developed. We compared the clinical effects of this bicarbonate/lactate-buffered neutral PDF and a lactate-buffered neutral PDF. METHODS AND DESIGN: Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF...
February 2016: Discovery Medicine
Jae Mo Park, Daniel M Spielman, Sonal Josan, Taichang Jang, Milton Merchant, Ralph E Hurd, Dirk Mayer, Lawrence D Recht
Hyperpolarized [1-(13)C]pyruvate MRS provides a unique imaging opportunity to study the reaction kinetics and enzyme activities of in vivo metabolism because of its favorable imaging characteristics and critical position in the cellular metabolic pathway, where it can either be reduced to lactate (reflecting glycolysis) or converted to acetyl-coenzyme A and bicarbonate (reflecting oxidative phosphorylation). Cancer tissue metabolism is altered in such a way as to result in a relative preponderance of glycolysis relative to oxidative phosphorylation (i...
May 2016: NMR in Biomedicine
Sylvie Opatrná, Anna Pöpperlová, Daniel Lysák, Radka Fuchsová, Ladislav Trefil, Jaroslav Racek, Ondrej Topolčan
Icodextrin peritoneal dialysis (PD) solution has been shown to increase interleukin-6 (IL-6) levels in PD effluent as well as leukocyte and mesothelial cell count. Mesothelial cells release cancer antigen 125 (CA125), which is used as a marker of mesothelial cell mass. This 1-year prospective study was designed to compare peritoneal effluent cell population, its inflammatory phenotype and biocompatibility biomarkers IL-6 and CA125 between icodextrin (E) and glucose bicarbonate/lactate (P) based PD solutions...
April 2016: Therapeutic Apheresis and Dialysis
Henrik Gutte, Adam Espe Hansen, Helle Hjorth Johannesen, Andreas Ettrup Clemmensen, Jan Henrik Ardenkjær-Larsen, Carsten Haagen Nielsen, Andreas Kjær
In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism...
2015: American Journal of Nuclear Medicine and Molecular Imaging
Talal El Imad, Lara El Khoury, Abdallah Sassine Geara
Lactic acidosis is the result of imbalance between the systemic formation of lactate and its hepatic metabolism. In cancer patients, lactic acidosis is mainly associated with hematologic malignancies (leukemia and lymphomas) and the mechanism is known as Warburg's effect. We report a 76-year-old male known to have hypertension and coronary artery disease, who presented with abdominal distension and lactic acidosis. His initial evaluation showed multiple liver masses that were biopsied and the patient was diagnosed with undifferentiated carcinoma of unknown primary, involving the liver...
November 2014: Saudi Journal of Kidney Diseases and Transplantation
Abdulgader H Albar, Hussein A Almehdar, Vladimir N Uversky, Elrashdy M Redwan
Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities...
2014: Current Protein & Peptide Science
Olga Sedlakova, Eliska Svastova, Martina Takacova, Juraj Kopacek, Jaromir Pastorek, Silvia Pastorekova
Acidic tissue microenvironment contributes to tumor progression via multiple effects including the activation of angiogenic factors and proteases, reduced cell-cell adhesion, increased migration and invasion, etc. In addition, intratumoral acidosis can influence the uptake of anticancer drugs and modulate the response of tumors to conventional therapy. Acidification of the tumor microenvironment often develops due to hypoxia-triggered oncogenic metabolism, which leads to the extensive production of lactate, protons, and carbon dioxide...
2014: Frontiers in Physiology
Sarah J Nelson, John Kurhanewicz, Daniel B Vigneron, Peder E Z Larson, Andrea L Harzstark, Marcus Ferrone, Mark van Criekinge, Jose W Chang, Robert Bok, Ilwoo Park, Galen Reed, Lucas Carvajal, Eric J Small, Pamela Munster, Vivian K Weinberg, Jan Henrik Ardenkjaer-Larsen, Albert P Chen, Ralph E Hurd, Liv-Ingrid Odegardstuen, Fraser J Robb, James Tropp, Jonathan A Murray
This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as [1-¹³C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds...
August 14, 2013: Science Translational Medicine
S Brucculeri, C Urso, G Caimi
Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis...
May 2013: La Clinica Terapeutica
Jae Mo Park, Lawrence D Recht, Sonal Josan, Milton Merchant, Taichang Jang, Yi-Fen Yen, Ralph E Hurd, Daniel M Spielman, Dirk Mayer
BACKGROUND: The metabolic phenotype that derives disproportionate energy via glycolysis in solid tumors, including glioma, leads to elevated lactate labeling in metabolic imaging using hyperpolarized [1-(13)C]pyruvate. Although the pyruvate dehydrogenase (PDH)-mediated flux from pyruvate to acetyl coenzyme A can be indirectly measured through the detection of carbon-13 ((13)C)-labeled bicarbonate, it has proven difficult to visualize (13)C-bicarbonate at high enough levels from injected [1-(13)C]pyruvate for quantitative analysis in brain...
April 2013: Neuro-oncology
Christoffer Laustsen, Jakob Appel Østergaard, Mette Hauge Lauritzen, Rikke Nørregaard, Sean Bowen, Lise Vejby Søgaard, Allan Flyvbjerg, Michael Pedersen, Jan Henrik Ardenkjaer-Larsen
BACKGROUND: This experimental study explores a novel magnetic resonance imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows monitoring of metabolic processes in seconds by >10 000-fold enhancement of the MR signal. The method has shown that the conversion of pyruvate to bicarbonate, i.e. pyruvate dehydrogenase (PDH) activity, is significantly altered in the myocardium already at the onset of diabetes, and the predominant Warburg effect is a valuable cancer maker via the lactate dehydrogenase (LDH) activity...
February 2013: Diabetes/metabolism Research and Reviews
Dirk Mayer, Yi-Fen Yen, Sonal Josan, Jae Mo Park, Adolf Pfefferbaum, Ralph E Hurd, Daniel M Spielman
In addition to cancer imaging, (13) C-MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation of cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported for doses commonly used in vivo, high substrate concentrations have lead to supraphysiological pyruvate levels that can affect the underlying metabolism and should be considered when interpreting results. With lactate serving as an important energy source for the heart and physiological lactate levels one to two orders of magnitude higher than for pyruvate, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing cardiac metabolism...
October 2012: NMR in Biomedicine
Ian F Robey, Natasha K Martin
BACKGROUND: The glycolytic nature of malignant tumors contributes to high levels of extracellular acidity in the tumor microenvironment. Tumor acidity is a driving force in invasion and metastases. Recently, it has been shown that buffering of extracellular acidity through systemic administration of oral bicarbonate can inhibit the spread of metastases in a mouse model for metastatic breast cancer. While these findings are compelling, recent assessments into the use of oral bicarbonate as a cancer intervention reveal limitations...
2011: BMC Cancer
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