Bibliografia Cancro

BIBLIOGRAFIA su CANCRO e pH
Le sperimentazioni dell’ISS (Istituto Sup. di Sanita’ – Italy) partono dall’evidenza che l’ambiente (Terreno)
in cui si sviluppa un tumore maligno è anch’esso acido !
e le vaccinazioni e certi farmaci, producono facilmente l’alterazione del terreno verso l’acidosi….
vedi: Terapia G. Puccio, dimostrazioni effetti del Bicarbonato di Sodio
E’ INDISPENSABILE per stare sempre BENE e’ l’assunzione quotidiana, per certi periodi, di acqua Basica a pH min. di 7,35 > 11 (almeno 1,5 lt)
Le bevande troppo saline e/o le bevande industriali, non vanno bevute giornalmente e/o spesso, anche e per le loro forti acidita’,
in quanto influiscono sull’alterazione dei giusti valori di pH dell’acqua del corpo.
L’acidosi e’ la base fisiologica del Cancro sulla quale scende lo stress del Conflitto Spirituale Irrisolto,
che ne e’ la Causa primaria attivando il Tumore nell’organo bersaglio dell’archetipo conflittuale.
Cancro = Combattere l’acidita’ per sconfiggerlo – Le ultime ricerche
Nutriterapia Biologica Metabolica x Cancro
 Circolazione sanguigna: prevenzione degli infarti e del cancro. I citrati eliminano calcificazioni arteriose. Gli ascorbati fanno il resto !
Paolo-Lissoni: i-segreti-della-pineale-anticancro-io-oncologo-vi-spiego-perche-la-medicina-esclude-di-bella/

Continua in: +  Biblio 3 +  Biblio 4  +  Bibliografia 1

pH and Chemotherapy – A., Raghunand N. B., Gillies RJ.
University of Arizona Health Sciences Center, Cancer Center Division, Tucson 85724-5024, USA.
In vivo pH measurements by magnetic resonance spectroscopy reveal the presence of large regions of acidic extracellular pH in tumours, with the intracellular pH being maintained in the neutral-to-alkaline range.
This acid-outside plasmalemmal pH gradient acts to exclude weak base drugs such as the anthracyclines and vinca alkaloids, a behaviour that is predicted by the decrease in octanol-water partition coefficients of mitoxantrone and doxorubicin with decreasing solution pH.
This pH gradient can be reduced or eliminated in mouse models of breast cancer by systemic treatment with sodium bicarbonate….. PMID: 11727930

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Articoli che documentano l’acidosi che caratterizza i tessuti tumorali
I Gliomi maligni esibiscono un’alterata regolazione dei pH, in confronto agli astrociti non trasformati
Malignant Gliomas display altered pH regu1ation byè NHE1 compared with non transformed astrocytes
Lee Anne McLean, Jane Roscoe, Nanna K. Jorgensen, Frederic A. Gorin, and Peter M. Cala – Departments of Human pHysiology and Neurology, School of Medicine, University of California, Davis, California 95616
Am J pHysiol Cell pHysiol 278: C676-C688, 2000.
I gliomi maligni esibiscono un’alterata regolazione del pH, in confronto agli astrociti non trasformati. I gliomi maligni esibiscono pH intracellulare (pHi) alcalino e il pH extracellulare (pHe) acido in confronto ad astrocití normali, malgrado l’aumento di produzione di H+.
Il pHe riduce la disponibilità dello ione bicarbonato HC03-, perciò riducendo la concentrazione dipendente, sia passiva che dinamica.
Questo implica che i gliomi sono dipendenti dalla concentrazione dinamica dello ione HC03- di bicarbonato, e indipendente dallo H+, come il tipo HC034H+ exchanger (NHE1).
In questo studio 4 gliomi a rapida proliferazione hanno esibito stabile e significativa alcalinità intracelluiare, superiore rispetto agli astrociti normali e un maggior riequilibrio dell’acidosi, dopo somministrazione di C021-1-1C03.
L’inibizione di NHE1 in assenza di C021HCO3 fu il risultato di un’alta acidificazione dei gliomi, laddove i normali astrociti non ne risentirono..
Quando veniva sospeso il C021-HCO3, il pHi degli astrociti aumentava, e ancora il pHi dei gliomi inaspettatamente diveniva acido; questo suggeriva un meccanismo di acidificazione dipendente dallo ione bicarbonato -HC03.
Le sequenze nucleotidiche dei DNA dei gliomi, dimostrarono che alterazioni genetiche non erano responsabili della funzione dell’NHE1.
Questi dati suggeriscono che l’attività dell’NHE1 è significativamente alterata nei gliomi e può essere utilizzata come bersaglio per lo sviluppo di terapie specifiche tumorali.

Cause e conseguenze dell’acidità nei tumori e implicazioni terapeutiche
Causes and consequences of tumour acidity and implications for treatment
Marion Stubbs, Paul M.I. McSheehy,Jhon R. Griffiths and C. Lindsay Bashford – Molecular Medicine: Today, January 2000 (vol.6)
Le cellule tumorali hanno un pH extracellulare (pHe) più basso delle cellule normali; questa è una caratteristica intrinseca dei genotipo tumorale, causata da alterazioni dovute sia al rilascio di acidi dalle cellule tumorali. sia all’assorbimento dell’acidosi extracellulare.
Un basso pH favorisce le cellule tumorali perché promuove l’invasività, laddove un alto pH extracellulare conferisce loro un vantaggio sulle cellule normali, riguardo alla crescita.
Gli approcci genetico molecolari hanno rivelato che l’ipossia indotta influenza la regolazione della glicolisi, un meccanismo potenziale importante per stabilire il fenotipo metabolico tumorale.
La comprensione dell’acidità dei tumore apre nuove opportunità terapeutiche.

Cause e conseguenze dell’ipossia e dell’acidità nei tumori
Causes and consequences of hypoxia and acidity in turnors – Novartis Foundatíon symposium
Robert J. Gillies – Arizone Cancer Center, University of Arizona, Tucson, Arizona, Usa  – Molecular Medicine Vol.7 N° 2 February 2001
Sia l’ipossia che l’acidità perpetuano un fenotipo tumorale più aggressivo.
Ipossia e acidosi inducono instabilità genetica. Ipossia e acidità inducono un fenotipo più metastatico e questo verosimilmente implica l’alterazione di una proteasi (catepsina) e una selezione metabolica. anche evidente tale che le cellule metastatiche producono tumori che sono più ipossici e con iperacidosi extracellulare. L’ipossia conferisce radio resistenza; il gradiente acido extracellulare può conferire chemio resistenza. La dinamica delle vescicole acide intracellulari è implicata sia nella chemio resistenza fisiologica che biochimica.

Cause e conseguenze dell’ipossia e dell’acidosi nel microambiente dei tumori
Causes and consequences of hypoxia and acidity in tumour rnicroenvironments
J.R. Griffiths – Glia 1994 Nov:12(3):196-210
1a riga: La prima e più importante scoperta nella fisiologia e biochimica dei tumore, fu l’anormale quantità di acido prodotta. Anche in presenza di ossigeno, l cancri solidi ottengono energia preferibilmente convertendo glucosio in acido lattico. Pagina 296, 17a riga: Il trattamento dei tumori con bicarbonato di sodio, può eliminare il gradiente di pH intra ed extracellulare e amplificare la risposta ai chemioterapici debolmente basici tipo  mitoxantrone. L’acidità tumorale è anche implicata nella chemio resistenza.
Ultimo capoverso: Le origini dell’acidosi tumorale si stanno chiarificando negli ultimi anni, e questo in una prospettiva terapeutica anticancro.

pH acido nei tumori, presupposto per nuove linee terapeutiche
Acid pH in tumors and its potential for therapeutic exploitation. Tannock IF, Rotin D. – Department of Medicine, Ontario Cancer Institute, Toronto, Canada. – Cancer Res 1989 Aug 15;49(16):4373-84 Related Articles, Books, LinkOut
La misurazione del pH nei tessuti ha evidenziato che il micro-ambiente è più acido nei tumori che nei tessuti normali; la produzione di acido lattico e l’idrolisi di ATIP nelle regioni ipossiche, rientrano probabilmente in questo meccanismo di iperacidità, insieme ad altri pattern metabolici.
Il pH acido allora, può influenzare lo sviluppo di nuove e relativamente specifiche terapie anticancro, mirate a regolare il pH intracellulare.

Potenziamento della terapia agendo sul pH del tumore
Enhancement of chemotherapy by manipulation of tumour pH.
Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ. – Arizona Cancer Center, Tucson 85724-5024, USA. – Br J Cancer 1999 Jun;80(7):1005-11 Related Articles, Books, Link Out
Il pH dei tumori solidi è significativamente più acido dei tessuti normali.
Un basso pH in vitro riduce la citotossicità dei chemioterapici debolmente basici., contribuendo ad una resistenza.
Il bicarbonato di sodio, si riporta nel lavoro, amplifica significativamente l’effetto della doxorubicina.
Questo lavoro rappresenta la dimostrazione in vivo (in pazienti neoplastici), della resistenza, già ben documentata in vitro e in via teorica, verso i chemioterapici debolmente basici.
Dynamics of bioelectric activity of the brain and erythrocyte ultrastructure after intravenous infusion of sodium bicarbonate to oncologic patients. – Davydova IG, Kassil’ VL, Raikhlin NT, Filippova NA. – Biull Eksp Biol Med 1992 Apr;113(4):352-5 Related Articles, Books, Link Out
Lo studio indica che le cellule di criceto possiedono attività regolatorie intracellulari, e che l’acidificazione cellulare gioca un ruolo nell’aumento di frequenza delle trasformazioni osservate nelle cellule coltivate in condizioni di acidità.
L’acidosi può essere evitata o ridotta artificialmente attraverso l’alcalinizzazione del sangue.

Effetto dell’alcalosi artificiale nell’attività dei cervello e nelle cellule dei sangue in pazienti oncologici
Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients. – Davydova IG, Kassil’ VL, Filippova NA, Barinov MV. – Vestn Ross Akad Med Nauk 1995;(4):24-5 Related Articles, Books, Link Out
Vengono studiati 40 pazienti oncologici, di differenti istotipi, sedi e dimensioni.
Il lavoro evidenzia che i pazienti hanno un’acidosi intracellulare generalizzata, che può essere diminuita con l’alcalinizzazione del plasma, con il risultato di ridurre le degenerazioni cellulari.

Diminuzione dei volume in presenza dello ione -HC03 in cellule di osteosarcoma
Regulatory volume decrease in the presence of HCO3- by single osteosarcoma cells UMR-106-01.
Star RA, Zhang BX, Loessberg PA, Muallem S. – Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9040. – J Biol Chem 1992 Sep 5;267(25):17665-9 Related Articles, Books, Link Out
Si registra simultaneamente la variazione di volume e di pH intracellulare, per studiare il ruolo di HC03- nella diminuzione dei volume cellulare.
L’aumento di pH intracellulare – risulta – coincide con una diminuzione del volume cellulare.
Appare evidente, in questo modo, il coinvolgimento dei Na+(HC03-) nella regolazione del volume cellulare.

L’acidificazione intracellulare è associata ad un aumento di trasformazioni morfologiche nelle cellule embrionali di criceto siriano
Intracellular acidification is associated with enhanced morpHological transformation in Syrian hamster embryo cells.
LeBoeuf RA, Lin PY, Kerckaert G, Gruenstein E. – Procter and Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45239-8707. – Cancer Res 1992 Jan 1;52(1):144-8 Related Articles, Books
Lo studio indica che le cellule di criceto possiedono attività regolatorie intracellulari, e che l’acidificazione cellulare gioca un ruolo nell’aumento di frequenza delle trasformazioni osservate nelle cellule coltivate in condizioni di acidità.

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1. Chetoacidosi diabetica grave Gamba G “Bicarbonate therapy in severe diabetic ketoacidosis.
A double blind, randomized, placebo controlled trial.” (Rev Invest Clin 1991 Jul-Sep;43(3):234-8).
2. Miyares Gomez A. in “Diabetic ketoacidosis in childhood: the first day of treatment
(An Esp Pediatr 1989 Apr;30(4):279-83).

3. Rianimazione cardiorespiratoria Levy MM “An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation” (Crit Care Clin 1998 Jul;14(3):457-83).

Vukmir RB Sodium bicarbonate in cardiac arrest: a reappraisal (Am J Emerg Med 1996 Mar;14(2):192-206).

4. Bar-JosepH G. “Clinical use of sodium bicarbonate during cardiopulmonary resuscitation–is it used sensibly?” (Resuscitation 2002 Jul;54(1):47-55).
5. Gravidanza Zhang L, “Perhydrit and sodium bicarbonate improve maternal gases and acid-base status during the second stage of labor” Department of Obstetrics and Gynecology, Xiangya Hospital, Hunan Medical University, Changsha 410008
6. Encefalomiopatia mitocondriale Maeda Y. “Perioperative administration of bicarbonated solution to a patient with mitochondrial encepHalomyopathy” (Masui 2001 Mar;50(3):299-303).
7. Emodialisi Avdic E. “Bicarbonate versus acetate hemodialysis: effects on the acid-base status” (Med Arh 2001;55(4):231-3).
8. Dialisi peritoneale Feriani M “Randomized long-term evaluation of bicarbonate-buffered CAPD solution.” (Kidney Int 1998 Nov;54(5):1731-8).
9. Tossicosi farmacologica Vrijlandt PJ “Sodium bicarbonate infusion for intoxication with tricyclic antidepressives: recommended inspite of lack of scient(ific evidence” Ned Tijdschr Geneeskd 2001 Sep 1;145(35):1686-9)
10. Knudsen K, “EpinepHrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning.” (Crit Care Med 1997 Apr;25(4):669-74).
11. Epatopatia Silomon M “Effect of sodium bicarbonate infusion on hepatocyte Ca2+ overload during resuscitation from hemorrhagic shock.” (Resuscitation 1998 Apr;37(1):27-32).

Mariano F. “Insufficient correction of blood bicarbonate levels in biguanide lactic acidosis treated with CVVH and bicarbonate replacement fluids” (Minerva Urol Nefrol 1997 Sep;49(3):133-6).

12. Interventi di chirurgia vascolare Dement’eva II “Calculation of the dose of sodium bicarbonate in the treatment of metabolic acidosis in surgery with and deep hypothermic circulatory arrest” (Anesteziol Reanimatol 1997 Sep-Oct;(5):42-4).Altra Bibliografia –

    References
    1 – Arieff, Allen I., and DeFronzo, Ralph, A., (Editors) Fluid, Electrolyte and Acid-Base Disorders, Churchill Livingstone, New York, NY, 1995.
    2 – Brecher Harold, and Brecher, Arline, Forty Something, A Consumer’s Guide to Chelation Therapy and Other Heart Savers, Sixteenth Edition, Healthsavers Press, Herndon, Virginia, 1996.
    3 – Cranton, Elmer, Bypassing Bypass, The New Technique of Chelation Therapy, Medex Publishers, Second edition, Trout Dale VA, March 1996.
    4 – Cohen, R.D., The Liver and Acid-Base Regulation, in Arieff, Allen I., and DeFronzo, Ralph, A., (Editors) Fluid, Electrolyte and Acid-Base Disorders, Churchill Livingstone, New York, NY, 1995.
    5 – Ensminger, Audrey H., Ensminger, M. E., Konlande, James E., Robson, John R.K., The Concise Encyclopedia of Foods & Nutrition, CRC Press, Boca Raton, FL, 1995.
    6 – Feldman, Elaine B., Nutrition and Diet in the Management of Hyperlipidemia and Atherosclerosis, in Modern Nutrition in Health and Disease, Volume 2, Lea & Febiger, Philadelphia, PA, 1994.
    7 – Fouque, Denis, and Kopple, Joel D., Total Parenteral Nutrition and Its Complications, in Arieff, Allen I., and DeFronzo, Ralph, A., (Editors) Fluid, Electrolyte and Acid-Base Disorders, Churchill Livingstone, New York, NY, 1995.
    8 – Gamble, James L., Jr., Acid-Base Physiology: A Direct Approach, The Johns Hopkins U. Press, Baltimore, MD., 1982.
    9 – Greger, R., and Windhorst, U., (Editors), Comprehensive Human Physiology, Volume 1 & 2, Springer Publishing, New York and Heidleberg, 1996.
    10 – Guton, Arthur C., and Hall, John, E., Textbook of Medical Physiology, Ninth Edition, W.B Sanders Company, Philadelphia, PA., 1996.
    11 – Halperin, Mitchell, L., Goguen, Jeannette M., Cheema-Dhadli, Surinder, and Kamel, Kamel S., Diabetic Emergencies, in Arieff, Allen I., and DeFronzo, Ralph, A., (Editors) Fluid, Electrolyte and Acid-Base Disorders, Churchill Livingstone, New York, NY, 1995.
    12 – Heart and Stroke Facts: 1996 Statistical Supplement, American Heart Association, Washington, DC, 1996.
    13 – Holtz, J., Peripheral Circulation: Fundamental Concepts, Comparative Aspects of Control in Specific Vascular Sections, and Lymph Flow, in Greger, R., and Windhorst, U., (Editors), Comprehensive Human Physiology, Volume 1 & 2, Springer Publishing, New York and Heidleberg, 1996.
    14 – Krall, Elizabeth, A., and Dawson-Huges, Bess, Osteoporosis, in Modern Nutrition in Health and Disease, Volumes 2, Lea & Febiger, Philadelphia, PA, 1994.
    15 – Kandel, Eric R., Schwartz, James H., and Jessell, Thomas M. (eds.), Principles of Neural Science, Third Edition, Appleton & Lange, Norwalk Connecticut, 1991.
    16 – Jänig, W., Regulation of the Lower Urinary Tract, in Greger, R., and Windhorst, U., (Editors), Comprehensive Human Physiology, Volume 1 & 2, Springer Publishing, New York and Heidleberg, 1996.
    17 – Kannel, William B., D’Agostino, Ralph, B. and Cobb, Janet, L., Effect of Weight on Cardiovascular Disease, American Journal of Clinical Nutrition, Volume 63, March 1996.
    18 – Kendrew, Sir John, (Editor in Chief), The Encyclopedia of Molecular Biology, Blackwell Science, NY and Oxford, 1994.
    19 – Lang, F., Acid-Base Metabolism, in Greger, R., and Windhorst, U., (Editors), Comprehensive Human Physiology, Volume 1 & 2, Springer Publishing, New York and Heidleberg, 1996.
    20 – The genomic analysis of response to lactic acidosis in human

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ALTRA BIBLIOGRAFIA (English)
[1] Vestn Ross Akad Med Nauk 1995;(4):24-5
[Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients]. [Article in Russian] Davydova IG, Kassil’ VL, Filippova NA, Barinov MV.
The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencepHalograpHy and peripHeral blood lympHocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencepHalograpHy, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lympHocytes.
These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization.
PMID: 7780336

[2] Br J Cancer 1999 Jun;80(7):1005-11
Enhancement of chemotherapy by manipulation of tumour pH.
Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ. Arizona Cancer Center, Tucson 85724-5024, USA.
The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues. In-vitro, low pH reduces the uptake of weakly basic chemotherapeutic drugs and, hence, reduces their cytotoxicity. This pHenomenon has been postulated to contribute to a  ‘pHysiological’ resistance to weakly basic drugs in vivo. Doxorubicin is  a weak base chemotherapeutic agent that is commonly used in combination chemotherapy to clinically treat breast cancers. This report demonstrates  that MCF-7 human breast cancer cells in vitro are more susceptible to doxorubicin toxicity at pH 7.4, compared to pH 6.8. Furthermore 31P-magnetic resonance spectroscopy (MRS) has shown that the pHe of MCF-7 human breast cancer xenografts can be effectively and significantly raised with sodium bicarbonate in drinking water.
The bicarbonate-induced extracellular alkalinization leads to significant improvements in the therapeutic effectiveness of doxorubicin against MCF-7 xenografts in vivo.
Although pHysiological resistance to weakly basic chemotherapeutics is well-documented in vitro and in theory, these data represent the first in vivo demonstration of this important pHenomenon.
PMID: 10362108

[3] Med Hypotheses 1999 May;52(5):367-72
Carcinogenesis and the plasma membrane. Stern RG, Milestone BN, Gatenby RA.
Department of Veterans Affairs Medical Center, and University of Arizona College of Medicine, Tucson, 85723, USA.sternr@u.arizona.edu
Presented is a two-stage hypothesis of carcinogenesis based on: (1) plasma membrane defects that produce abnormal electron and proton efflux; and (2) electrical uncoupling of cells through loss of intercellular communication. These changes can be induced by a wide variety of stimuli including chemical carcinogens, oncoviruses, inherited and/or acquired  genetic defects, and epigenetic abnormalities. The resulting loss of electron/proton homeostasis leads to decreased transmembrane potential, electrical microenvironment alterations, decreased extracellular pH, and increased intracellular pH. This produces a positive feedback loop  to enhance and sustain the proton/electron efflux and loss of intercellular communication.
Low transmembrane potential is functionally related to rapid cell cycling, changes in membrane structure, and malignancy.
Intracellular alkalinization affects a variety of pH-sensitive systems including glycolysis, DNA synthesis, DNA transcription and DNA repair, and promotes genetic instability, accounting for the accumulation of genetic defects seen in malignancy. The abnormal microenvironment results in the selective survival and proliferation of malignant cells at the expense of contiguous normal cell populations.
PMID: 10416941

[4] FASEB J 2000 Nov;14(14):2185-97
Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated pHenotypes.
Reshkin SJ, Bellizzi A, Caldeira S, Albarani V, Malanchi I, Poignee M, Alunni-Fabbroni M, Casavola V, Tommasino M. Department of General and Environmental pHysiology, University of Bari, Bari, Italy.
In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is transformation specific. In NIH3T3 cells in which transformation can be turned on and followed by induction of the HPV16 E7 oncogene expression, we demonstrate that cytoplasmic alkalinization is an early event and was driven by stimulation of Na+/H+ exchanger activity via an increase in the affinity of the intracellular NHE-1 proton regulatory site.
Annulment of the E7-induced cytoplasmic alkalinization by specific inhibition of the NHE-1, acidification of culture medium, or clamping the pHi to nontransformed levels prevented the development of later transformed pHenotypes such as increased growth rate, serum-independent growth, anchorage-independent growth, and glycolytic metabolism. These findings were verified in human keratinocytes (HPKIA), the natural host of HPV.
Results from both NIH3T3 and HPKIA cells show that alkalinization acts on pathways that are independent of the E2F-mediated transcriptional activation of cell cycle regulator genes. Moreover, we show that the transformation-dependent increase in proliferation is independent of the concomitant stimulation of glycolysis. Finally, treatment of nude mice with the specific inhibitor of NHE-1, DMA, delayed the development of  HPV16-keratinocyte tumors. Our data confirm that activation of the NHE-1 and resulting cellular alkalinization is a key mechanism in oncogenic transformation and is necessary for the development and maintenance of the transformed pHenotype.
PMID: 11053239

Studi relativi al potere antiacido del bicarbonato di sodio nei tumori:
Anne McLean, “Malignant gliomas display altered pH regu1ation byè NHE1 compared with non transformed astrocytes  (Am J Physiol Cell Physiol 278: C676-C688, 2000).
Marion Stubbs, “Causes and consequences of tumour acidity and implications for treatment”, Molecular Medicine: Today, January 2000 (vol.6).
Robert J. Gillies, “Causes and consequences of hypoxia and acidity in turners – Novartis Foundatíon symposium”, Molecular Medicine Vol.7 N° 2 February 2001; “Causes and consequences of hypoxia and acìdity in tumour microenvironments”.
J.R. Griffiths, “Causes and consequences of hypoxia and acìdity in tumour microenvironments”, Glia 1994 Nov:12(3):196-210.
Tannock, I.F., “Acid pH in tumors and its potential for therapeutic exploitation”, Cancer Res 1989 Aug 15;49(16):4373-84.
Raghunand, N., “Enhancement of chemotherapy by manipulation of tumour pH”, Br J Cancer 1999 Jun;80(7):1005-11.
Davydova, I.G., “Dynamics of bioelectric activity of the brain and erythrocyte ultrastructure after intravenous infusion of sodium bicarbonate to oncologic patients.” Biull Eksp Biol Med 1992 Apr;113(4):352-5.
Davydova, I.G., “Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients”, Vestn Ross Akad Med Nauk 1995;(4):24-5.
Star, R.A., “Regulatory volume decrease in the presence of HCO3- by single osteosarcoma cells UMR-106-01”, J Biol Chem 1992 Sep 5;267(25):17665-9.
LeBoeuf, R.A., “Intracellular acidification is associated with enhanced morphological transformation in Syrian hamster embryo cells”, Cancer Res 1992 Jan 1;52(1):144-8.
Raghunand, N., “Acute metabolic alkalosis enhances response of C3H mouse mammary tumors to the weak base mitoxantrone.” Neoplasia. 2001 May-Jun;3(3):227-35.
Raghunand, N., “pH and chemotherapy pH and chemotherapy” Novartis Found Symp. 200 1;240:199-21 l; discussion 265 -8.
Raghunand, N., “Enhancement of chemotherapy by manipulation of tumour pH.” Br J Cancer. 1999 Jun;80(7):1005-1 I.
Raghunand, N., “Tumor acidity, ion trapping and chemotherapeutics. IL pll-dependent partition coefficients predict importance of ion trapping on pharmaeokinetics of weakly basic chemotherapeutie agents.” Bíochem Pharmacol. 2003 Oct 1;66(7):1219-29.”
Mahoney, B.P., “Tumor acidity, ion trapping and chemotherapeutics. I. Acid plì affects the distribution of ehemotherapeutic agents in vitro.” Biochem Phannacol. 2003 Oct 1;66(7):1207-18.
Schornack, P.A., “Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors.” Neoplasia. 2003 Mar-Apr;5(2):135-45.
Giffles, R.J., “MRI of the tumor microenvironment.” J Magn Reson Imaging 2002 Dec; 16(6):75 l.
Torigoe, T., “Vacuolar H(+)-ATPase: funetional mechanisms and potential as a target for cancer chemotherapy.” Anticancer Drugs. 2002 Mar; 13 (3):23 7-43.
Griffiths, J.R., “Why are cancers acidic? A carrier-mediated diffusion model for H+ transport in the interstitial fluid.” Novartis Found Symp. 200 1;240:46-62; discussion 62-7, 152-3.
Webb, S.D., “Modelling tumour acidity and invasion.” Novartis Found Symp. 2001;240:169-8 l; discussion 181-5.
Gillies, R.J., “The tumour microenvironment: causes and consequences of hypoxia and acidity. Introduction.” Novartis Found Symp. 200 1;240:1-6.
Gillies, R.J., “Causes and consequences of hypoxia and acidity in tumors” Novartis Foundation symposium. Trends Mol Med. 2001 Feb;7(2):47-9.
Griffiths, JR. “Causes and consequences of hypoxia and acidity in tumour microenvironments. Bioessays. 2001 Mar;23(3):295-6.
Gillies, R.J., “Causes and effects of heterogeneous perfusion in tumors.” Neoplasia. 1999 Aug; 1 (3):197-207.
Stubbs, M., “Causes and consequences of tumour acidity and implications for treatment.” Mol Med Today. 2000 Jan;6(1):15-9Stubbs, M., “Causes and consequences of acidic ph in tumors: a magnetic resonance study.” Adv. Enzyme Regul. 1999;39;13-30.
Webb, S.D., “Mathematical modelling of tumour acidity: regulation of intracellular pH.” J Theor Biol. 1999 Jan 21; 196(2);237-50.
Yamagata, M., “The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase.” Br J Cancer. 1998 Jun;77(11):1726~3 I.
Martin, G.R., “Non invasive measurement of interstitial pH profiles in normal and neoplastie tissue using fluorescence ratio imaging microscopy.” Cancer Res. 1994 Nov 1;54(21):5670-4.
Boyer, M.J., “Regulation of intracellular pH in subpopulations of cefis derived from spheroids and solid tumours.” Br J Cancer. 1993 Nov;68(5):890-7.
Newell, K., “Studies with gIyeolysis-dericient celIs suggest that production of lactic acid is not the only cause of tumor acidity.”

Altra Bibliografia:

1 – Spinazze S, Schrijvers D. Metabolic emergencies. Crit Rev Oncol Hematol. 2006 Apr;58:79-89. Epub 2005 Dec 7 – Medline

2 –  Flombaum CD. Metabolic emergencies in the cancer patient. Semin Oncol. 2000;27:322-334 – Medline

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Tratto da: http://www.mayoclinicproceedings.com/content/81/11/1506.1.full

Bibliografia e letture raccomandate:  Continua su:  Biblio 3 +  Biblio 4 + Nutriterapia per il cancro

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