scholarly journals Selective lysis of breast carcinomas by simultaneous stimulation of sodium channels and blockade of sodium pumps

Oncotarget ◽  
2018 ◽  
Vol 9 (21) ◽  
pp. 15606-15615 ◽  
Author(s):  
Harry J. Gould ◽  
Jack Norleans ◽  
T. David Ward ◽  
Chasiti Reid ◽  
Dennis Paul
Keyword(s):  
Sodium Channels ◽  
Breast Carcinomas ◽  
Sodium Pumps ◽  
Simultaneous Stimulation ◽  
Selective Lysis ◽  
Stimulation Of

scholarly journals Emergency Use of Targeted Osmotic Lysis for the Treatment of a Patient with Aggressive Late-Stage Squamous Cell Carcinoma of the Cervix

2021 ◽  
Vol 28 (3) ◽  
pp. 2115-2122
Author(s):  
Harry J. Gould ◽  
Paige R. Miller ◽  
Samantha Edenfield ◽  
Kelly Jean Sherman ◽  
Chad K. Brady ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Carcinoma Cells ◽  
Advanced Stage ◽  
Broad Application ◽  
Sodium Pumps ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Osmotic Lysis ◽  
Pharmacological Blockade ◽  
Stimulation Of

Upregulation of voltage-gated sodium channels (VGSCs) and Na+/K+-ATPase (sodium pumps) is common across most malignant carcinomas. Targeted osmotic lysis (TOL) is a developing technology in which the concomitant stimulation of VGSCs and pharmacological blockade of sodium pumps causes rapid selective osmotic lysis of carcinoma cells. This treatment of cervical carcinoma is evidence that TOL is a safe, well-tolerated and effective treatment for aggressive advanced carcinomas that has the potential to extend life without compromising its quality. TOL is likely to have broad application for the treatment of advanced-stage carcinomas.

scholarly journals Allosteric stimulation of voltage-dependent sodium channels by brevetoxin in cultured bovine adrenal medullary cells

1992 ◽  
Vol 58 ◽  
pp. 268
Author(s):  
Akihiko Wada ◽  
Yasuhito Uezono ◽  
Tomoaki Yuhi ◽  
Hideyuki Kobayashi ◽  
Nobuyuki Yanagihara ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Adrenal Medullary Cells ◽  
Voltage Dependent ◽  
Stimulation Of ◽  
Medullary Cells

scholarly journals Targeted Osmotic Lysis of Highly Invasive Breast Carcinomas Using Pulsed Magnetic Field Stimulation of Voltage-Gated Sodium Channels and Pharmacological Blockade of Sodium Pumps

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1420
Author(s):  
Dennis Paul ◽  
Paul Maggi ◽  
Fabio Del Piero ◽  
Steven D. Scahill ◽  
Kelly Jean Sherman ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Electrical Current ◽  
Normal Breast ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Reduce Tumor Growth ◽  
Osmotic Lysis ◽  
Stimulation Of

Concurrent activation of voltage-gated sodium channels (VGSCs) and blockade of Na+ pumps causes a targeted osmotic lysis (TOL) of carcinomas that over-express the VGSCs. Unfortunately, electrical current bypasses tumors or tumor sections because of the variable resistance of the extracellular microenvironment. This study assesses pulsed magnetic fields (PMFs) as a potential source for activating VGSCs to initiate TOL in vitro and in vivo as PMFs are unaffected by nonconductive tissues. In vitro, PMFs (0–80 mT, 10 msec pulses, 15 pps for 10 min) combined with digoxin-lysed (500 nM) MDA-MB-231 breast cancer cells stimulus-dependently. Untreated, stimulation-only, and digoxin-only control cells did not lyse. MCF-10a normal breast cells were also unaffected. MDA-MB-231 cells did not lyse in a Na+-free buffer. In vivo, 30 min of PMF stimulation of MDA-MB-231 xenografts in J/Nu mice or 4T1 homografts in BALB/c mice, concurrently treated with 7 mg/kg digoxin reduced tumor size by 60–100%. Kidney, spleen, skin and muscle from these animals were unaffected. Stimulation-only and digoxin-only controls were similar to untreated tumors. BALB/C mice with 4T1 homografts survived significantly longer than mice in the three control groups. The data presented is evidence that the PMFs to activate VGSCs in TOL provide sufficient energy to lyse highly malignant cells in vitro and to reduce tumor growth of highly malignant grafts and improve host survival in vivo, thus supporting targeted osmotic lysis of cancer as a possible method for treating late-stage carcinomas without compromising noncancerous tissues.

scholarly journals Stimulation of Protein Kinase C Inhibits Bursting in Disease-Linked Mutant Human Cardiac Sodium Channels

Circulation ◽  
2003 ◽  
Vol 107 (25) ◽  
pp. 3216-3222 ◽  
Author(s):  
M. Tateyama ◽  
J. Kurokawa ◽  
C. Terrenoire ◽  
I. Rivolta ◽  
R.S. Kass
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sodium Channels ◽  
Kinase C ◽  
Cardiac Sodium Channels ◽  
Stimulation Of

scholarly journals Reflex cardiorespiratory events from esophageal origin are heightened by preterm birth

2017 ◽  
Vol 123 (2) ◽  
pp. 489-497 ◽  
Author(s):  
Stéphanie Nault ◽  
Nathalie Samson ◽  
Charlène Nadeau ◽  
Djamal Djeddi ◽  
Jean-Paul Praud
Keyword(s):  
Preterm Birth ◽  
Arterial Pressure ◽  
Random Order ◽  
Neonatal Infection ◽  
Full Term ◽  
Simultaneous Stimulation ◽  
C Fibers ◽  
C Fiber ◽  
Cardiorespiratory Reflexes ◽  
Stimulation Of

The involvement of gastroesophageal refluxes in cardiorespiratory events of preterm infants remains controversial. While a few studies in full-term newborn animals have shown that stimulation of esophageal receptors leads to cardiorespiratory reflexes, the latter remain largely unknown, especially after premature birth. The present study aimed to 1) characterize the cardiorespiratory reflexes originating from esophageal receptors in newborn lambs and 2) test the hypotheses that preterm birth enhances reflex cardiorespiratory inhibition and that C-fibers are involved in these reflexes. Eight full-term lambs and 10 lambs born 14 days prematurely were studied. Following surgical instrumentation, a 6-h polysomnography was performed without sedation to record electrocardiogram, respiratory movements, arterial pressure, laryngeal constrictor muscle activity, state of alertness, and hemoglobin oxygen saturation. Five esophageal stimulations of the upper and/or lower esophagus, including rapid balloon inflation and/or HCl injection, were performed in random order. A second recording was performed in full-term lambs 24 h later, after C-fiber blockade by capsaicin. Results confirmed that esophageal stimulations induced inhibitory cardiorespiratory reflexes combined with protective mechanisms, including laryngeal closure, swallowing, coughing, increased arterial pressure, and arousal. Preterm birth heightened cardiorespiratory inhibition. The strongest cardiorespiratory inhibition was observed following simultaneous stimulation of the lower and upper esophagus. Finally, cardiorespiratory inhibition was decreased after C-fiber blockade. In conclusion, esophageal stimulation induces inhibitory cardiorespiratory reflexes, which are partly mediated by C-fibers and more pronounced in preterm lambs. Clinical relevance of these findings requires further studies, especially in conditions associated with increased cardiorespiratory events, e.g., neonatal infection. NEW & NOTEWORTHY Preterm birth heightens the cardiorespiratory events triggered by esophageal stimulation. The most extensive cardiorespiratory events are induced by simultaneous stimulation of the proximal and distal esophagus.

scholarly journals Nervous rhythm arising from rivalry of antagonistic reflexes: Reflex stepping as outcome of double reciprocal innervation

1913 ◽  
Vol 86 (587) ◽  
pp. 233-261 ◽  
Keyword(s):  
Afferent Nerve ◽  
The Other ◽  
Present Communication ◽  
Simultaneous Stimulation ◽  
Afferent Nerves ◽  
Wide Range ◽  
Contralateral Muscle ◽  
Stimulation Of

The observations with which the present communication deals were met with in experiments continuing those on reciprocal innervation of symmetrical muscles. In my previous paper on that subject it had been reported that in regard to symmetrical extensors of the knee the ratio borne by intensity of the ipsilateral inhibition to the contralateral excitation is such that with equal stimuli to right and left symmetrical afferent nerves there is inhibitory suppression of contraction in both the muscles. In other words, under double reciprocal innervation the ipsilateral inhibition by each nerve completely overcomes the contralateral excitation of the other. It was shown that this mutual suppression holds over a wide range of the scale of intensities of stimulation. It was also shown that with quite weak stimuli a simultaneous stimulation of both nerves, stimuli being equal in intensity, often results in concurrent contraction of both muscles. Indeed, with quite weak stimuli, the effect of stimulation of each afferent nerve by itself is, in the decerebrate preparation, usually contraction of the ipsilateral as well as of the contralateral muscle. This being so, it is evident that at some point in the scale of intensities of stimulation there should be a place below which contralateral excitation is stronger than ipsilateral inhibition, whereas above it ipsilateral inhibition is stronger than contralateral excitation.

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