142 cases of nasopharyme cancer were treated by radiotherapy using the method of sample external radotherapy and method of external radio therapy and method of external radio therapy in combining with the source of radium applied in situ supported by a foam rubber hoder. Results showed that by combining method reduced the risk of recurrence occurred later and in a location other than the primary cancer. The technique was carried with low cost and easy looking for materials.
Therapeutics ; Carcinoma ; Nasopharyngeal Neoplasms ; Monensin ; Radium

Recent reports revealed that the Na+/-Ca2+ exchangers and feet structures of sarcoplasmic reticulum (SR) are located in close vicinity in the specific compartment. Therefore, we investigated the possibility that the Na+/-Ca2+ exchanger may decrease the tension development by transporting the Ca2+ out of the cell right after it released from SR, on the basis of this anatomical proximity. We examined the negative force-frequency relationship of the developed tension in the electrically field stimulated left atria of postnatal developing rat (1, 3 day, 1 week and 4 week old after birth). Cyclopiazonic acid (3 X 10(-5) M) treatment decreased the developed tension further according to postnatal age. Monensin (3 X 10(-6) M) treatment did not increase the maximal tension in 4 week-old rat, preserving negative staircase, while the negative staircase in the younger rat were flattened. Ca2+ depletion in the buffer elicited more suppression of the maximal tension according to the frequency in all groups except the 4 week-old group. The % decrease of the maximal developed tension of 4 week-old group at 1 Hz to that of 0.1 Hz after Na+ and Ca2+ depletion was only a half of those of the younger groups. Taken together, it is concluded that the Na+/-Ca2+ exchange transports more Ca2+ released from SR out of the cell in proportion to the frequency, and this is responsible for the negative staircase effect of the rat heart.
Animals ; Foot ; Heart* ; Monensin ; Rats* ; Sarcoplasmic Reticulum

Frequency-force relationships (FFR) were studied in electrically field stimulated rat left atria (LA) by reducing the stimulation frequency from resting 3 Hz to test frequencies (0.1-1 Hz) for 5 minutes. The twitch amplitudes of LA elicited the typical negative staircases with 3-phased changes: the initial rapid increase, the second decrease and the following plateau at test frequencies. Verapamil (3 X 10-5 M) pretreatment elicited frequency-dependent suppression of the twitch amplitudes, exaggerating the negative staircase. Monensin pretreatment enhanced not the peak but the plateau amplitudes in a concentration-dependent manner. When the Na+-Ca2+ exchange was blocked by Na+ and Ca2+ depletion in the Krebs Hensleit buffer (0 Na+-0 Ca2+ KHB), the twitch amplitudes increased in a frequency-dependent manner, changing the negtive staircase into the positve one. Meanwhile, the 0 Na+-0 Ca2+ KHB applicationinduced enhancement was strongly suppressed by caffeine (5 mM) pretreatment. Only dibucaine among the local anesthetics increased the basal tone during frequency reduciton. There were no differences in 45Ca uptakes between 0.3 Hz and 3 Hz stimulation except at 1 min when it was significantly low at 0.3 Hz than 3 Hz, illustrating net Ca2+ losses. Monensin pretreatment enhanced the rate of this Ca2+ loss. Taken together, it is concluded that Na+-Ca2+ exchange extrudes more SR released Ca2+ out of the cell in proportion to the frequency, resulting in the negative rate staircase in the rat LA.
Anesthetics, Local ; Animals ; Caffeine ; Dibucaine ; Monensin ; Rats ; Verapamil

It has been postulated that the intracellular taurine is co-transported with Na+ down a concentration gradient and prevents the intracellular accumulation of sodium. It is therefore, expected that an elevated level of intracellular taurine prevents the sodium-promoted calcium influx to protect the cellular damages associated with sodium and calcium overload. In the present study, we evaluated the effects of intra- and extracellular taurine on the myocardial Na+ and Ca++ contents and the cardiac functions in isolated rat hearts which were loaded with sodium by monensin, a Na+/-ionophore. Monensin caused a dose-dependent increase in intracellular Na+ accompanied with a subsequent increase in intracellular Ca++ and a mechanical dysfunction. In this monensin-treated heart, myocardial taurine content was decreased with a concomitant increase in the release of taurine. The monensin-induced increases in intracellular Na+, Ca++ and depression of cardiac function were prevented in the hearts of which taurine content had been increased by high-taurine diet. Conversely, in the hearts of which taurine concentration gradient had been decreased by addition of taurine in the perfusate, the monensin-induced increases in Na+, Ca++ and functional depression were accelerated. These results suggest that taurine, depending on the intra-extracellular concentration gradient, can affect intracellular sodium and calcium concentrations, and that an increased intracellular taurine may play a role in protection of myocardial dysfunction associated with the sodium and calcium overload.
Animals ; Calcium ; Depression ; Diet ; Heart* ; Monensin ; Rats* ; Sodium ; Taurine*

The underlying mechanism commonly applicable for both the positive and negative force-frequency relationships (FFR) was pursued in left atria (LA) of rat and rabbit. The species differences in the roles of Na+/Ca2+ exchanger and sarcoplasmic reticulum (SR), which are major intracellular Ca2+ regulatory mechanisms in the heart, were examined in the amplitude accommodation to the frequency that changed from 3 Hz to the variable test frequencies for 5 minutes in the electrically field stimulated left atria (LA) of rat and rabbit. Norepinephrine strongly increased the frequency-related amplitude accommodation in both of rat and rabbit LA, while monensin, oubain or the reduced Na+ and 0 mM Ca2+ containing Tyrode solution increased the frequency-related amplitude accommodation only in the rabbit LA. Monenisn was also able to increase the frequency-related amplitude accommodation only in 1-day old rat LA but not in 4-week old rat LA that had 75% less Na+/Ca2+ exchanger with 97% higher SR than 1-day old rat LA. Taken together, it is concluded that the differences in the prevalence between myocardial Na+/Ca2+ exchanger and SR in the amplitude accommodation to the frequency-change determine the difference in the FFR between rat and rabbit heart.
Animals ; Heart ; Monensin ; Norepinephrine ; Prevalence ; Rats* ; Sarcoplasmic Reticulum

Recently, indirect evidences suggest that Na-Ca exchange mechanism is involved in bone resorption. To study this suggestion, effects of several drugs which increase the intracellular sodium concentration by different mechanisms on the PTH-induced bone resorption were analysed employing organ culture. Ulnae and radii were removed from 19-day fetal rats, prelabelled by subcutaneous injection of 200micron Ci 45CaCl2 on the 17th day of gestation, and then explanted on the membrane filters in organ culture dishes. For studying the effects of amiloride, ouabain, monensin, and veratridine on the PTH-induced bone resorption, control group was cultured in BGJb media containing PTH (0.4U/ml) while experimental group was cultured in BGJb media containing PTH and drugs. The effects of drugs on the PTH-induced bone resorption were observed by the ratios of %-release of 45Ca between paired control and experimental groups. The results were as follows: 1. 45Ca release was significantly increased by PTH (0.4U/ml) at 48 and 72 hours of culture. 2. Amiloride, at concentration of 500micronM, significantly inhibited the PTH-induced bone resorption after 48 and 72 hours of culture. 3. Ouabain, at concentration of 0.1mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 0.5mM and 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. 4. Monensin, at concentration of 500nM, significantly inhibited PTH-induced bone resorption after 72 hours of culture. 5. Veratridine, at concentration of 0.5mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. Taken altogether, these results suggest that Na-Ca exchange mechanism playa role in PTH-induced bone resorption.
Amiloride ; Animals ; Bone Resorption* ; Injections, Subcutaneous ; Membranes ; Monensin ; Organ Culture Techniques* ; Ouabain ; Pregnancy ; Rats ; Sodium* ; Ulna ; Veratridine

BACKGROUND: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. METHODS: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. RESULTS: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-G1 phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. CONCLUSION: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.
Apoptosis ; Apoptosis Regulatory Proteins ; Autophagy ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; Caspase 3 ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Death ; DNA ; Epidermal Growth Factor ; Flow Cytometry ; Lung ; Lung Neoplasms ; Lysosomes ; Monensin ; Phosphotransferases ; Poly(ADP-ribose) Polymerases ; Proteins ; Quinazolines ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Sirolimus ; Stress, Physiological ; TOR Serine-Threonine Kinases ; Erlotinib Hydrochloride