Newsgroup: it.salute
Titolo: Effetti del bicarbonato sulla crescita tumorale

 
 
 
 Degli effetti positivi del bicarbonato sulla proliferazione delle cellule 
 tumorali:
 
 
 The effects of CA IX catalysis products within tumor microenvironment.
 
http://www.ncbi.nlm.nih.gov/pubmed/24168032
 
 
 
 Il testo completo e' liberamente scaricabile in pdf, ma lo si puo' 
 anche leggere comodamente online a questo link:
 
 
http://www.biosignaling.com/content/11/1/81
 
 
 di  particolare  rilievo le  Figure 4 e  5, dopo   il paragrafo
 "Bicarbonate  ion  contributes  to cancer  cells  proliferation" 
 (trad. gli ioni bicarbonato contribuiscono  alla  proliferazione
 delle  cellule tumorali)  in cui   si  evidenzia  un   netto   e 
 significativo  incremento della crescita delle cellule  tumorali 
 esposte al bicarbonato:
 
 
http://www.biosignaling.com/content/11/1/81/figure/F4
 
 
http://www.biosignaling.com/content/11/1/81/figure/F5
 

 medline...
 
come rimedio "alternativo" il bicarbonato fa schifo persino in materia di giardinaggio: tutti lo consigliano per la lotta ai parassiti, ma nessuno ti dice che devi usarlo all'ombra e ad una temperatura inferiore ai 20 gradi, se no ammazza pure le foglie delle piante!
;)

 medline...
 
 
  io invece  prevedo  un link  ad  un  famoso  articolo su medline che
  che scommetto nessuno dei membri dello Staff  (luminaROTFL compreso) 
  deve aver letto perche' citato piu' volte come prova d'efficacia del-
  la nota pseudocura.
 

 ;)
 
  ...tu non capisci l'universo alternativo: eliminate le foglie, eliminato il
  parassita, eliminato il paziente eliminato il tumore.

   parassita, eliminato il paziente eliminato il tumore.
 
perbacco, hai ragione!

   
http://www.biosignaling.com/content/11/1/81/figure/F5
 
 
Molto interessante, grazie per averlo segnalato.
 
Tuttavia quello è UN articolo, non la luce su tutta la faccenda.
 
In particolare, la proliferazione delle singole cellule tumorali non
è affatto incompatibile con l'effetto di blocco delle metastasi (già
riscontrato negli animaloidi con le somministrazioni di bicarbonato),
perché dal fallimento degli antiangiogenici sappiamo che quando le
cellule tumorali non riescono a sopravvivere nel tumore originario,
esse metastatizzano. Quindi non mi stupirebbe che tentare una terapia
acidificante nel paziente canceroso possa mandargli più rapidamente
in metastasi il tumore di cui soffre. Peraltro, il fatto che le cellule
cancerose possano sopravvivere bene in un ambiente a pH 8, fa pensare
che il bicarbonato possa inibire per qualche tempo le metastasi ma
al prezzo di favorire la proliferazione locale delle cellule tumorali
invece di ucciderle. Forse sarà davvero così, ma non ci potrà essere
una risposta certa a questi dubbi e contraddizioni finché non si farà
il relativo esperimento sull'animale vero affetto da cancro vero (es.
cagna con carcinoma mammario spontaneo): solo quello sarebbe dirimente.
 
Bye,
 
   *GB*

 la nota pseudocura.
 
Quello che leggono o non leggono loro, ha poca importanza. L'importante
č che gli scienziati (non gli scemziati) riescano finalmente a capire
se agire sul pH tissutale possa servire o no a combattere il cancro.
 
Infatti i cosiddetti imperativi etici non permettono a un nuovo Mengele
di verificare subito e con sicurezza la cosa trattando con bicarbonato
o acido lattico qualche centinaio di pseudo-umani (di razza inferiore)
affetti da tumori maligni.
 
Bye,
 
   *GB*

 cagna con carcinoma mammario spontaneo): solo quello sarebbe dirimente.
 
  Gia', ma intanto abbiamo un dato sperimentale che fa a botte con
  il razionale dell'alcalinizzazione degli alternativi e  quel che
  e' peggio e' che non si osserva un nulla de facto ma addirittura
  un effetto positivo sulla proliferazione tumorale.

 tumorali:
 
Studio non credibile sovvenzionato da Bigpharma (tuo padrone).
I seguenti studi dicono esattamente il contrario :
 
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):15-9
 
Stubbs, 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.”
 
 
 
 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.
 
 Fluorescence ratio imaging of interstitial pH in solid tumours:
effect of glucose on spatial and temporal gradients.
 
 Dellian M, Helmlinger G, Yuan F, Jain RK. - Edwin L Steele
Laboratory, Department of Radiation Oncology, Massachusetts General
Hospital, Harvard Medical School, Boston 02114, USA.
 
 Tumour pH plays a significant role in cancer treatment. However,
because of the limitations of the current measurement techniques,
spatially and temporally resolved pH data, obtained non-invasively in
solid tumours, are not available. Fluorescence ratio imaging
microscopy (FRIM) has been used previously for noninvasive, dynamic
evaluation of pH in neoplastic tissue in vivo (Martin GR, Jain RK
1994, Cancer Res., 54, 5670-5674). However, owing to problems
associated with quantitative fluorescence in thick biological tissues,
these studies were limited to thin (50 microns) tumours. We,
therefore, adapted the FRIM technique for pH determination in thick
(approximately 2 mm) solid tumours in vivo using a pinhole
illumination-optical sectioning (PIOS) method. Results show that (1)
steep interstitial pH gradients (5 microns resolution), with different
spatial patterns, exist between tumour blood vessels; (2) pH decreased
by an average of 0.10 pH units over a distance of 40 microns away from
the blood vessel wall, and by 0.33 pH units over a 70 microns
distance; (3) the maximum pH drop, defined as the pH difference
between the intervessel midpoint and the vessel wall, was positively
correlated with the intervessel distance; (4) 45 min following a
systemic glucose injection (6 g kg-1 i.v), interstitial pH gradients
were shifted to lower pH values by an average of 0.15 pH units, while
the spatial gradient (slope) was maintained, when compared with
preglucose values. This pH decrease was not accompanied by significant
changes in local blood flow. pH gradients returned to near-baseline
values 90 min after glucose injection; (5) interstitial tumour pH
before hyperglycaemia and the glucose-induced pH drop strongly
depended on the local vessel density; and (6) sodium bicarbonate
treatment, either acute (1 M, 0.119 ml h-1 for 3 h i.v.) or chronic
(1% in drinking water for 8 days), did not significantly change
interstitial tumour pH. Modified FRIM may be combined with other
optical methods (e.g. phosphorescence quenching) to evaluate
non-invasively the spatial and temporal characteristics of
extracellular pH, intracellular pH and pO2 in solid tumours. This will
offer unique information about tumour metabolism and its modification
by treatment modalities used in different cancer therapies.
 
 J Pain Symptom Manage 1996 Jul;12(1):11-7 Related Articles, Books,
LinkOut 
 
 Comment in:  J Pain Symptom Manage. 1997 Jun;13(6):316-8
 
 Effects of induced metabolic alkalosis on perception of dyspnea
during flow-resistive loading.
 
 Taguchi N, Ishikawa T, Sato J, Nishino T. - Department of
Anesthesiology, School of Medicine, Chiba University, Japan.
 
 Treatment of dyspnea in patients with advanced cancer is an important
issue. The purpose of the present study was to assess the effect of
induced-metabolic alkalosis produced by administration of sodium
bicarbonate on dyspneic sensation. In seven healthy subjects, dyspnea
was induced by having them breathe with a flow-resistive load (24 cm
H2O/L/sec) for 6 min before and after administration of sodium
bicarbonate (0.5 mmol/kg, per os+2 mmol/kg, IV). The intensity of
dyspnea was rated using a visual analogue scale (VAS). The VAS scores
and minute ventilation during loaded breathing after administration of
sodium bicarbonate were significantly lower than those before
administration of sodium bicarbonate. These results indicate that
induced metabolic alkalosis may alleviate the intensity of dyspneic
sensation by a reduction in ventilatory drive.
 
 Diminuzione del volume in presenza di -HCO3 in cellule di
osteosarcoma
 
 Si registra simultaneamente la variazione di voume e di Ph
intracellulare, per studiare il ruolo di HCO3- nella diminuzione del
volume cellulare.
 
L’aumento di Ph intracellulare – risulta – coincide con una
diminuzione del volume cellulare.
 
Appare evidente, in questo modo, il coinvolgimento del Na+ (HCO3-)
nella regolazione del volume cellulare.
 
 J Biol Chem 1992 Sep 5;267(25):17665-9 Related Articles, Books,
LinkOut
 
 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.
 
 The technique for the simultaneous recording of cell volume changes
and pHi in single cells was used to study the role of HCO3- in
regulatory volume decrease (RVD) by the osteosarcoma cells UMR-106-01.
In the presence of HCO3-, steady state pHi is regulated by Na+/H+
exchange, Na+ (HCO3-)3 cotransport and Na(+)-independent Cl-/HCO3-
exchange. Following swelling in hypotonic medium, pHi was reduced from
7.16 +/- 0.02 to 6.48 +/- 0.02 within 3.4 +/- 0.28 min. During this
period of time, the cells performed RVD until cell volume was
decreased by 31 +/- 5% beyond that of control cells (RVD overshoot).
Subsequently, while the cells were still in hypotonic medium, pHi
slowly increased from 6.48 +/- 0.02 to 6.75 +/- 0.02. This increase in
pHi coincided with an increase in cell volume back to normal (recovery
from RVD overshoot or hypotonic regulatory volume increase (RVI)). The
same profound changes in cell volume and pHi after cell swelling were
observed in the complete absence of Cl- or Na+, providing HCO3- was
present. On the other hand, depolarizing the cells by increasing
external K+ or by inhibition of K+ channels with quinidine, Ba2+ or
tetraethylammonium prevented the changes in pHi and RVD. These
findings suggest that in the presence of HCO3-, RVD in UMR-106-01
cells is largely mediated by the conductive efflux of K+ and HCO3-.
Removal of external Na+ but not Cl- prevented the hypotonic RVI that
occurred after the overshoot in RVD. Amiloride had no effect, whereas
pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
(DIDS) strongly inhibited hypotonic RVI. Thus, hypotonic RVI is
mediated by a Na+(out)-dependent, Cl(-)-independent and
DIDS-inhibitable mechanism, which is indicative of a Na+(HCO3-)3
cotransporter. This is the first evidence for the involvement of this
transporter in cell volume regulation. The present results also stress
the power of the new technique used in delineating complicated cell
volume regulatory mechanisms in attached single cells.
 
 Effetto dell’alcalosi artificiale nell’attività del cervello e nelle
cellule del sangue in pazienti oncologici: 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.
 
 Vestn Ross Akad Med Nauk 1995;(4):24-5 Related Articles, Books,
LinkOut
 
 [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.
 
 Cancer Res 1989 Jan 1;49(1):205-11 Related Articles, Books, LinkOut
 
 Requirement of the Na+/H+ exchanger for tumor growth.
 
 Rotin D, Steele-Norwood D, Grinstein S, Tannock I. - Department of
Medicine and Medical Biophysics, Ontario Cancer Institute, Toronto,
Canada.
 
 The Na+/H+ exchanger is involved in a variety of cellular processes,
including regulation of intracellular pH and possibly the control of
cell growth and proliferation. To study the role of the Na+/H+
exchanger in tumor growth, human sodium proton exchanger-deficient
(HSPD) mutants were derived from the human bladder carcinoma cell line
MGH-U1 (EJ) by the proton suicide selection technique (J. Pouyssegur
et al., Proc. Natl. Acad. Sci. USA, 81: 4833-4837, 1984). The HSPD
cells were approximately 40% larger and contained approximately 70%
more DNA than the parental cells. They were unable to grow in vitro in
the absence of bicarbonate at pH less than 7.0, whereas the parental
cells grew well at pH greater than or equal to 6.6. This difference in
acid sensitivity was abolished in the presence of bicarbonate. In
contrast to the parental MGH-U1 cells, the Na+/H+-deficient HSPD cells
either failed to grow tumors, or showed severely retarded tumor growth
when implanted into immune-deprived mice. This difference in tumor
growth was not attributed to differences in cell size and DNA content,
because Na+/H+ exchange-competent large cells (HLC), derived during
the same proton suicide selection process as the HSPD cells, grew
tumors at a rate close to that of the parental cells. Cells derived
from the few tumors which grew after implantation of HSPD mutant cells
were revertants which had regained Na+/H+ activity. HSPD cells also
failed to form spheroids in culture, and the only spheroid formed
consisted of revertant cells which had regained both Na+/H+ exchange
activity and tumorigenic capacity. These results suggest that the
Na+/H+ exchanger is important for tumor growth.
 
 Eur J Biochem 1987 Dec 30;170(1-2):43-9 Related Articles, Books
 
 Properties of the Na+-dependent Cl-/HCO3- exchange system in U937
human leukemic cells.
 
 Ladoux A, Krawice I, Cragoe EJ Jr, Abita JP, Frelin C. - Institut
National de la Sante et de la Recherche Medicale Unite 204, Hopital
Saint-Louis, Paris, France.
 
 U937 cell possess two mechanisms that allow them to recover from an
intracellular acidification. The first mechanism is the
amiloride-sensitive Na+/H+ exchange system. The second system involves
bicarbonate ions. Its properties have been defined from intracellular
pH (pHi) recovery experiments, 22Na+ uptake experiments, 36Cl- influx
and efflux experiments. Bicarbonate induced pHi recovery of the cells
after a cellular acidification to pHi = 6.3 provided that Na+ ions
were present in the assay medium. Li+ or K+ could not substitute for
Na+. The system seemed to be electroneutral. 22Na+ uptake experiments
showed the presence of a bicarbonate-stimulated uptake pathway for Na+
which was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonate.
The bicarbonate-dependent 22Na+ uptake component was reduced by
depleting cells of their internal Cl- and increased by removal of
external Cl-. 36Cl- efflux experiments showed that the presence of
both external Na+ and bicarbonate stimulated the efflux of 36Cl- at a
cell pHi of 6.3. Finally a 36Cl- uptake pathway was documented. It was
inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonate (K0.5 = 10
microM) and bicarbonate (K0.5 = 2 mM). These results are consistent
with the presence in U937 cells of a coupled exchange of Na+ and
bicarbonate against chloride. It operates to raise the intracellular
pH. Its pHi and external Na+ dependences were defined. No evidence for
a Na+-independent Cl-/HCO3- exchange system could be found. The
Na+-dependent Cl-/HCO3- exchange system was relatively insensitive to
(aryloxy)alkanoic acids which are potent inhibitors of
bicarbonate-induced swelling of astroglia and of the Li(Na)CO3-/Cl-
exchange system of human erythrocytes. It is concluded that different
anionic exchangers exist in different cell types that can be
distinguished both by their biochemical properties and by their
pharmacological properties.
 
 L’acidificazione intracellulare è associata ad un aumento di
trasformazioni morfologiche nelle cellule embrionali di criceto
siriano
 
 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.
 
 Cancer Res 1992 Jan 1;52(1):144-8 Related Articles, Books
 
 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.
 
 A series of studies has indicated that the frequency of morphological
transformation induced by chemical carcinogens in early passage Syrian
hamster embryo (SHE) cells is significantly higher when these cells
are cultured in medium of reduced bicarbonate concentration and pH
(6.70) compared with cells cultured in medium of higher pH. It has
also been shown that intercellular gap junctional communication is
decreased in these cells when they are cultured at pH 6.70 compared
with medium of higher pH. The purpose of the studies reported here was
to characterize the effect of changing extracellular pH on
intracellular pH in SHE cells. The frequency of morphological
transformation induced by benzo(a)pyrene was established at various
extracellular pHs and compared with intracellular pH values. Cells
cultured in medium of pH ranging from 6.70 to 7.35 were loaded with
the pH-sensitive fluorescent dye
2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein, and either the
steady-state intracellular pH values or the kinetics of change in
intracellular pH following refeeding of the cultures with medium of pH
ranging from pH 6.70 to pH 7.35 was monitored via image analysis
techniques. Results from these studies indicate that, at culture
medium pH above 6.95, SHE cells were relatively insensitive to changes
in extracellular pH, maintaining an intracellular pH of 7.30 to 7.35
in medium containing 0% serum or pH 7.05 to 7.10 in medium containing
20% fetal bovine serum. At extracellular pHs below 6.95, intracellular
pH decreased and, in the presence of serum, equilibrated with
extracellular pH. The decrease in intracellular pH was closely
associated with an increase in benzo(a)pyrene-induced morphological
transformation frequency observed in parallel studies. These results
indicate that SHE cells have active intracellular pH regulatory
activities and suggest that intracellular acidification plays a role
in the increased frequency of transformation observed in SHE cells
cultured under acidic conditions.
 
Dinamiche dell’attività bioelettrica del cervello e
dell’ultrastruttura eritrocitaria, dopo infusione di bicarbonato di
sodio in pazienti oncologici
 
Partendo dall’ipotesi di un’acidosi intracellulare generalizzata, 23
paziente affetti da neoplasia in diverse sedi anatomiche e di
differenti tipi istologici, sono stati trattati con NaHCO3.
 
L’alcalosi metabolica ha indotto miglioramento nellEEG e nelle
alterazioni di aggregazione eritrocitaria.
 
Il risultato conferma l’ipotesi di partenza.
 
Biull Eksp Biol Med 1992 Apr;113(4):352-5
 
[Dynamics of bioelectric activity of the brain and erythrocyte
ultrastructure after intravenous infusion of sodium bicarbonate to
oncologic patients]. - [Article in Russian]
 
Davydova IG, Kassil' VL, Raikhlin NT, Filippova NA.
 
23 patients with malignant tumors of different location and
histogenesis were investigated. There were no metastases in 9 cases.
10 patients had metastases in regional areas and 4--distant. The
results were compared with those obtained in 4 patients with
nonmalignant diseases. EEG, blood gases, plasma acid--base balance and
ultrastructure of erythrocytes were explored before and after
intravenous infusion of 4.2% sodium bicarbonate solution. The
metabolic alkalosis induced amelioration of EEG, which was changed
basically, the condense of pre-membrane layer disappeared or decreased
in erythrocytes, and disaggregation of erythrocytes took place in
cancer patients vs those with nonmalignant tumors. The results confirm
the suggestion of generalized intracellular acidosis in malignant
tumor patients. This acidosis can be temporarily avoided or diminished
artificially by blood alkalosis.
 
Liver Transpl Surg 1999 Mar;5(2):151-2 Related Articles, Books
 
Prolonged lactic acidosis after extended hepatectomy under in situ
hypothermic perfusion.
 
Davidson BR, Rai R. - Department of Surgery, The Royal Free Hospital,
London, England.
 
 46-year-old woman underwent right extended hepatectomy under total
vascular occlusion with in situ hypothermic perfusion for colorectal
metastasis. Immediately after surgery, she developed severe lactic
acidosis, which required correction with sodium bicarbonate solution
and ventilatory support for 36 hours. After 2 days, her lactate
normalized, and the acidosis was corrected. She made an uneventful
recovery. Persistent lactic acidosis after major hepatic resection
under in situ hypothermic perfusion is a rare but reversible problem.
 
Cancer Res 1998 May 1;58(9):1901-8 Related Articles, Books, LinkOut
 
Heterogeneity of intracellular pH and of mechanisms that regulate
intracellular pH in populations of cultured cells.
 
Lee AH, Tannock IF. - Department of Medical Biophysics, Ontario Cancer
Institute, Toronto, Canada.
 
Cells within solid tumors are known to exist in a microenvironment
that may be acidic and depend on membrane-based mechanisms (Na+/H+
antiport and Na+-dependent Cl-/HCO3- exchanger) that regulate
intracellular pH (pHi). We have used the fluorescent pH indicator
2',7'-bis-(2-carboxyethyl) 5 (and 6)-carboxyfluorescein and flow
cytometry to study the distribution of pHi and the activity of these
pHi-regulating mechanisms among populations of murine mammary sarcoma
(EMT6), human breast cancer (MCF-7), and Chinese hamster ovary cells
exposed to different levels of extracellular pH (pHe). Cells were
exposed to Na+ buffer in the presence or absence of HCO3- and of
5-(N-ethyl-N-isopropyl)-amiloride (a potent inhibitor of the Na+/H+
antiport) to determine the relative importance of each exchanger in
the regulation of pHi. Our results indicate that: (a) the distribution
of pHi at any value of pHe is broader than can be accounted for by
machine noise; (b) cells maintain levels of pHi that are higher than
pHe under acidic conditions; (c) the distribution of pHi is narrower
when the Na+-dependent Cl-/HCO3- exchanger is active; and (d)
populations that are derived from selected cells with values of pHi at
lower and higher ends of the pHi distribution generate pHi
distributions that are similar to those of controls, suggesting a
stochastic variation in the activity of membrane-based mechanisms that
regulate pHi. 
Our data suggest that the Na+-dependent Cl-/HCO3- exchanger is the
dominant mechanism for regulation of pHi under moderately acidic
conditions such as may occur in the microenvironment of solid tumors
 
 
-- 
ConsulenzeAlternative® , By Marco Antolini
Opinionista e critico della Medicina Ufficiale
Naturopata & Consulente per lo sviluppo delle M.N.C.
Gestore del gruppo : it-alt.salute.tumori
www.mednat.org
 - 
www.zapcandida.com
 

tumors.” Neoplasia. 1999 Aug; 1 (3):197-207.
 
Ma si, mettili anche 500 volte tanto chi vuoi che controlli?
Mo va a cagher.
 
 

 I seguenti studi dicono esattamente il contrario :
 
 
AHAHAHAHAHHA sei un buffone oltre che cialtrone... hai fatto un 
copiancolla di un mare di roba sperando che nessuno avesse voglia di 
leggere e ti sei smerdato da solo.
Di la verità, alla fin fine sei stipendiato da bigpharma e ne fai  
pubblicità.
 
-- 
Alla fine vince l'entropia
 
 

 I seguenti studi dicono esattamente il contrario :
 
 


 pH.” Br J Cancer. 1999 Jun;80(7):1005-1 I.
 
  Li hai postati tu eh..
 
  Chi ti ha passato 'sta bibliografia, qualche squilibrato che
  va dicendo che il cancro è un fungo ?
  No perchè ora che mi sovviene neanche di questo  parlano gli
  studi che hai postato.
 

 tumori:
 
Bella figura di cacca che hai fatto. 
 
 

 Bella figura di cacca che hai fatto. 
 
Ma guarda che per lui e' la norma, eh...
 
bye G.L.
-- 
Da i.d.c.tutela:
P.S. Quando ci sarà lo switch-off, avrò problemi anche col
monitor del PC? Ho visto che è collegato in modalità analogica.

Non ho mai effettuato questo tipo di indagini
 
Hai voglia a copiaincollare lavori che dicono tutt'altro rispetto a
quello che sostieni tu...
 
Il giochino non funziona.

 In sintesi la candida non è un post hoc ma un propter hoc.
 
  se il cancro e' un fungo e il fungo e'  il  cancro com'e'
  che nell'80% dei pazienti degli articoli che hai postato
  cancro e fungo sono ben distinti ?