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C W Song

Publications and source records attributed to C W Song.

At least 55 records · Page 3Linked to original sources
PubMed1997

Interlaboratory variation in oxygen tension measurement by Eppendorf "Histograph" and comparison with hypoxic marker.

BACKGROUND AND OBJECTIVES: The median of pO2 values in tumor measured by Eppendorf "Histograph" with a needle-type electrode has been used as a prognostic indicator in cancer patients. However, it is not established that a pretreatment measured pO2 value can be used as a universal predictor of local control probability, because the variation in pO2 values, especially in hypoxic tissue, among institutes may not allow comparison of measured "absolute pO2 values." The purpose of this study was to examine the variation in oxygen tension measurement by Eppendorf "Histograph" among six laboratories using a single batch of mice and tumors and the same detailed protocol. These results were also compared to the immunohistochemical staining of 2-nitromidazole adducts. METHODS: C3H mice bearing FSaII murine fibrosarcoma subcutaneously were shipped to all laboratories, and the oxygen status in tumors and in normal subcutis was examined using Eppendorf "Histograph" and immunohistochemical hypoxic marker. RESULTS: All laboratories showed that the FSaII tumor was hypoxic with at least 77% of measured points under 10 mmHg in pO2 and with a median pO2 value less than that of normal subcutis. These results were further confirmed immunohistochemically. These findings are interpreted as evidence that the pO2 values measured by Eppendorf "Histograph" can be useful. However, the median values of tumor pO2 varied from 1.5 mmHg to 5.6 mmHg among the laboratories, and pO2 of normal subcutis also varied from 28 mmHg to 38 mmHg. There were also significant differences in hypoxic fraction, defined as the fraction under a given oxygen partial pressure (i.e., under 2.5, 5, or 10 mmHg), among institutes. CONCLUSIONS: Caution needs to be exercised in using the absolute, median, or distribution of pO2 values measured by the Eppendorf "Histograph" to compare the data between laboratories or to predict the radiation response in an individual subject.

Animals↗
PubMed1997

Mapping of new recessive cataract gene (lr2) in the mouse.

A new strain of mice with cataracts was developed in BALB/cHeA and STS/A recombinant inbred strain, CXS4 (D). In this study the mapping of spontaneous autosomal recessive cataract mutation is described. This mutation was characterized by ruptures of the lens nucleus, vitreous chamber through the posterior capsule, and the vacuolization of the lens. For the linkage analysis, we produced two kinds of backcross progenies, (BALB/cHeA x D)F1 and (STS/A x D)F1 females crossed to D male mice. The gene (lr2, lens rupture2) was mapped to the central part of Chromosome(Chr) 14, 0.7 +/- 0.7 cM from the micosatellite marker D14Mit28.

Age Factors↗
PubMed1997

Endoscopic resection of submucosal tumor of the esophagus: results in 62 patients.

BACKGROUND AND STUDY AIMS: Although most submucosal tumors of the esophagus are benign, reliable exclusion of leiomyosarcoma requires histological analysis. However, this is rarely possible with an endoscopic forceps biopsy. In an attempt to establish the diagnosis, and as an alternative to surgery, we present here our experience with the endoscopic removal of submucosal tumors of the esophagus using two different techniques. PATIENTS AND METHODS: Sixty-two patients (38 men, 24 women, mean age 47) with submucosal tumors of the esophagus were treated endoscopically. If the tumor was less than 2 cm in diameter, polypoid, or showed a round protrusion with at least moderate elevation at endoscopy, a conventional snare polypectomy was performed. If the tumor was larger than 2 cm in diameter or only mildly elevated, the technique of modified endoscopic incisional enucleation was carried out, consisting of complete stripping of the overlying tissue followed by tumor enucleation using an electrocautery snare and a coagulation electrode. RESULTS: Based on these criteria, 36 patients underwent conventional snare polypectomy, and 25 received endoscopic incisional enucleation; complete resection of the tumor was possible in these 61 cases. In one patient, only partial removal was possible, due to firm and wide adhesions to the surrounding tissue. The tumor diameters ranged from 0.6 cm to 7.5 cm, with a mean value of 1.9 cm; 14 tumors measured more than 3 cm. At histopathology, the resected specimens were found to be 56 leiomyomas, four granular cell tumors, one neurogenic tumor, and one cyst. No serious complications such as perforation or massive bleeding occurred, and oozing bleeding, which was encountered in three patients, was easily managed by endoscopic electrocoagulation. During the follow-up period (mean 38.4 months, range 3-107 months) no recurrence was observed in any of the 61 patients who received complete resections. CONCLUSION: This method of endoscopic removal of submucosal tumors of the esophagus appears to be safe and effective in experienced hands. It allows complete histopathological workup, and at the same time complete removal of the tumor. The method can be considered as an alternative to surgery in symptomatic cases.

Adult↗
PubMed1997

A new hereditary cataract mouse with lens rupture.

A new cataract model originated in a recombinant inbred (RI) strain, CXS4 or CXSD (D), between BALB/cHeA(BALB/c or C) and STS/A(STS or S) mice. Opacity appeared as a white pinpoint focus in unpigmented eyes of albino mice from 5 weeks old. All the mice were bilaterally affected by 14 weeks old. They were fully viable and fertile. There was no sex difference in incidence of cataract. Histologically, the 3-4 months old mice showed vacuoles in the lens cortex. The vacuoles were spread all over the lens cortex in advanced cases. Ruptures of the lens nucleus to the vitreous chamber was a typical occurrence. For elucidation of the mode of inheritance, F1 hybrids (CXD and SXD) and backcross progenies [(CXD)F1XD and (SXD)F1XD] were analysed. No affected mice were observed in F1 hybrids. In backcross progenies, the segregation ratio of affected and normal mice was close to 1:1 in both matings. We conclude that the cataract is inherited by an autosomal single recessive gene. This mutant gene is provisionally named 'lens rupture 2' (gene symbol 1r2, Mouse Genome Database Accession No. MGD-JNUM-37399). The new cataract model mouse will be a good tool for the genetic analysis and molecular biological study of cataractogenesis.

Age Factors↗
PubMed1997

Double-blind placebo-controlled study of cisapride in patients with nonspecific esophageal motility disorder accompanied by delayed esophageal transit.

BACKGROUND: Nonspecific esophageal motility disorder (NEMD) represents a difficult therapeutic challenge because of the heterogeneous nature of the esophageal motor functions. We studied the effects of cisapride on the esophageal symptoms and esophageal motor function in a group of patients with NEMD showing delayed esophageal transit. METHODS: Seventy eligible patients were entered into a 4-week, double-blind randomized comparison of 10 mg of cisapride or placebo, four times daily. Symptom assessment, esophageal manometry after wet swallows, and esophageal scintigraphy after intake of a liquid and solid bolus were performed in each patient before and after treatment. RESULTS: After 4 weeks of treatment cisapride significantly increased the prevalence of esophageal peristaltic contractions (percentage of total contractions, P < 0.05 versus base line and placebo) and significantly improved esophageal emptying of the solid bolus (P < 0.05 versus placebo) but not of the liquid bolus. Placebo did not have any significant effects versus base line on these variables. Both placebo and cisapride improved the distal esophageal amplitude versus base line (no significant intergroup differences). Symptom scores were significantly reduced after 4 weeks of treatment versus base line in both groups (no significant intergroup differences except for heartburn and regurgitation, P < 0.05). On global evaluation of treatment, significantly more patients in the cisapride group were rated as markedly or moderately improved, when compared with placebo. CONCLUSIONS: The results of the present study showed that cisapride is effective and well tolerated in patients with NEMD accompanied by delayed esophageal transit. Symptomatic improvement may possibly be related to its beneficial action on the esophageal body by increasing the number of peristaltic contractions and esophageal emptying of solids.

Adult↗
PubMed1997

Effect of cisapride and renzapride on gastrointestinal motility and plasma motilin concentration in dogs.

The effects of cisapride and renzapride (BRL 24924), on plasma concentration of motilin and gastroduodenal motility were studied in seven dogs with implanted force transducers in the antrum and duodenum. In the interdigestive state, the i.v. administration of cisapride (5 mg) or renzapride (5 mg) administered in phase I resulted in a prompt and marked increase in plasma motilin concentration and in gastroduodenal motility. Mean plasma motilin levels during the first 30 min after cisapride and after renzapride injection were 85.0 +/- 6.5 (+/- S.E.) and 96.1 +/- 6.3 pM., respectively. These values were significantly greater (P < .001) than those for the corresponding time period of the control cycle, 52.2 +/- 5.6 and 57.4 +/- 5.3 pM (mean phase III level, 120 +/- 8.1 pM), respectively. The increases in the motilin level after cisapride or renzapride coincided with significant increases in contractile activities of the antrum to 43.2 +/- 5.3% and 44.9 +/- 4.6% and of the duodenum to 28.4 +/- 3.1% and 34.2 +/- 2.2% of phase III activity (100%) from that in the corresponding control period, 0.7 +/- 0.4% and 0.2 +/- 0.1%, respectively. The changes in both plasma motilin and motility in response to the two drugs were abolished completely by the i.v. administration of atropine. The drugs also enhanced the meal-induced contractile activities of the antrum as well as the duodenum but failed to influence the postprandial plasma motilin concentration. We conclude that cisapride and renzapride have similar effects on plasma motilin and gastroduodenal motility: 1) the two drugs increase plasma motilin levels and stimulate gastroduodenal motility in the interdigestive state, and 2) in the digestive state, both drugs enhance motility without influencing the plasma motilin levels.

Animals↗
PubMed1997

Improvement of tumor oxygenation status by mild temperature hyperthermia alone or in combination with carbogen.

The effects of mild temperature hyperthermia (MTH) on the oxygenation and radioresponse in rodent tumors were investigated. FSall tumors grown in the legs of C3H mice and R3230 AC tumors grown in the legs of Fischer rats were heated with a water bath and the partial pressure of oxygen (pO2) was determined using the microelectrode method. In FSall tumors, the pO2 measured immediately after heating at 41.5 degrees C for 1 hour was markedly higher than that in the control tumors, whereas heating at higher temperatures for 1 hour decreased the tumor oxygenation. In R3230 AC tumors, heating at 41.5 degrees C for 1 hour caused a moderate increase in the pO2 and heating at 42.5 degrees or 43.5 degrees C for 30 minutes markedly increased the pO2. However, heating at 42.5 degrees C or higher temperatures for 1 hour decreased the pO2 in the R3230 AC tumors. The improvement of oxygenation in FSall tumors by heating at 41.5 degrees C for 1 hour increased the radiation-induced cell death in these tumors. The combination of carbogen breathing with MTH was far more potent than carbogen breathing or MTH alone in increasing tumor oxygenation and potentiating the radiation effect in FSall tumors.

Adenocarcinoma↗
PubMed1996

Mild temperature hyperthermia combined with carbogen breathing increases tumor partial pressure of oxygen (pO2) and radiosensitivity.

The partial pressure of oxygen (pO2) of FSaII tumors grown in the leg of C3H mice significantly improved when the tumors were heated by immersing the tumor-bearing legs in a water bath at 41.5 degrees C for 60 min. The tumor pO2 also substantially increased when the tumor-bearing mice breathed carbogen (95% O2:5% CO2). Additionally, mild hyperthermia followed by carbogen breathing further increased the tumor pO2 and increased radiation cytotoxicity as assessed by the in vivo/in vitro excision assay for surviving FSaII cells. It was concluded that mild hyperthermia in combination with carbogen breathing is potentially useful to reoxygenate radioresistant hypoxic cells and improve the radiotherapy of human tumors.

Animals↗
PubMed1996

Radiosensitization of hypoxic tumor cells in vitro by nitric oxide.

PURPOSE: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied. METHODS AND MATERIALS: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined. RESULTS: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/ NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions. CONCLUSIONS: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated.

Aerobiosis↗
PubMed1996

Vascular thermal adaptation in tumors and normal tissue in rats.

PURPOSE: The vascular thermal adaptation in the R3230 adenocarcinoma, skin and muscle in the legs of Fischer rats was studied. METHODS AND MATERIALS: The legs of Fischer rats bearing the R3230 AC adenocarcinoma (subcutaneously) were heated once or twice with a water bath, and the blood flow in the tumor, skin and muscle of the legs was measured with the radioactive microsphere method. RESULTS: The blood flow in control R3230 AC tumors was 23.9 ml/100 g/min. The tumor blood flow increased about 1.5 times in 30 min and then markedly decreased upon heating at 44.5 degrees C for 90 min. In the tumors preheated 16 h earlier at 42.5 degrees C for 60 min, reheating at 44.5 degrees C increased the tumor blood flow by 2.5-fold in 30 min. Contrary to the decline in blood flow following an initial increase during the 44.5 degrees C heating without preheating, the tumor blood flow remained elevated throughout the 90 min reheating at 44.5 degrees C. These results indicated that thermal adaptation or thermotolerance developed in the tumor vasculatures after the preheating at 42.5 degrees C for 60 min. The magnitude of vascular thermal adaptation in the tumors 24 h and 48 h after the preheating, as judged from the changes in blood flow, were smaller than that 16 h after the preheating. Heating at 42.5 degrees C for 60 min induced vascular thermal adaptation also in the skin and muscle, which peaked in 48 h and 24 h, respectively, after the heating. CONCLUSION: Heating at 42.5 degrees C for 1 h induced vascular thermal adaptation in the R3230 AC tumor, skin, and muscle of rats that peaked 16-48 h after the heating. When the tumor blood vessels were thermally adapted, the tumor blood flow increased upon heating at temperatures that would otherwise reduce the tumor blood flow. Such an increase in tumor blood flow may hinder raising the tumor temperature while it may increase tumor oxygenation.

Adaptation, Physiological↗
PubMed1996

Effect of intracellular acidity and ionomycin on apoptosis in HL-60 cells.

The aim was to investigate in detail the influence of intracellular pH (pHi) and intracellular Ca2+ concentration ([Ca2+]i) on apoptosis in HL-60 human promyelocytic leukaemia cells. The pHi was controlled by changing the pH of media as well as by interfering with the pHi regulatory mechanisms with 3-amino-6-chloro-5-(1-homopiperidyl)-N-(diaminomethylene) pyrazincarboxamide (HMA; an inhibitor of Na+/H+ antiport), 4-diiosothiocyanatostilbene-2,2'disulfonic acid, (DIDS; an inhibitor of Na(+)-dependent HCO3-/Cl- exchange) and nigericin (a K+ ionophore). The [Ca2+]i was increased with ionomycin, a Ca2+ ionophore. The apoptosis of HL-60 cells was measured with conventional agarose gel electrophoresis for DNA fragmentation and also with the release of 3H from 3H-thymidine-labelled DNA. Based on the magnitude of DNA fragmentation and 3H release at different pHi, it was shown that apoptosis occurred in HL-60 cells when the pHi was lowered from normal pHi of 7.4 to about 7.2-6.7 with a peak increase at pHi 6.8-6.9. Addition of 4 microM ionomycin to RPMI 1640 medium, which contained 615 microM Ca2+, elevated the apoptosis in the cells. Such an increase in apoptosis by ionomycin in HL-60 cells appeared to result from both an increase in [Ca2+]i and from a decline in pHi. The results indicate that the acidic intratumour environment may greatly affect the response of neoplastic tissues to hyperthermia, radiation and chemotherapeutic drugs which cause apoptosis.

Apoptosis↗
PubMed1996

Tumour pO2 can be increased markedly by mild hyperthermia.

We have studied the feasibility of improving tumour oxygenation with hyperthermia at modest temperatures which are achievable with the use of presently available clinical hyperthermia machines. FSaII tumours grown s.c. in the leg of C3H mice and R3230 AC tumours grown s.c. in the leg of Fischer rats were heated with a water bath and the tumour pO2 was determined with an Eppendorf pO2 histograph. The median pO2 in 7-8 mm diameter control FSaII tumours was 6.5 +/- 0.5 mmHg and it increased to 16.6 +/- 1.1 mmHg when the tumours were heated at 41.5 degrees C for 1 h. The median pO2 in 10 mm diameter control R3230 AC tumours was 3.7 +/- 0.3 mmHg. Heating at 42.5 degrees C for 30 min increased the median pO2 in the R3230 AC tumours to 12.2 +/- 1.8 mmHg. The pO2 in FSaII tumours measured 24 h after heating at 41.5 degrees C for 1 h was still higher than the pO2 before heating. The % frequency of pO2 values lower than 5 mmHg decreased markedly when the tumours were heated at the modest temperatures mentioned above. Modest temperature hyperthermia (MTH) may be an efficient and useful means to improve the oxygenation of human tumours.

Animals↗
PubMed1995

Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study.

PURPOSE: Since 1985, the University of Minnesota Hospital and Clinic has investigated the efficacy and safety of 8 MHz radiofrequency (RF) capacitive hyperthermia using the Thermotron RF-8. This study reports the thermometric and clinical results of 119 patients treated with RF hyperthermia in combination with radiotherapy (RT). METHODS AND MATERIALS: Of 119 patients, 69 received high-dose RT and 50 patients received low-dose RT because of previous irradiation to the treatment site. The most common anatomic sites treated were within the pelvic cavity or head and neck area. Thirty-three percent and 24% of tumors treated were > 7 cm and > 10 cm in largest diameter, respectively. Forty percent of the patients had deep-seated tumors (depth > 6 cm). Hyperthermia was given as soon as possible after RT twice weekly, allowing at least 72 h between treatments. The objective was to raise intratumoral temperatures to 42-43 degrees C or above for 30-50 min while keeping normal tissue temperatures below 40-41 degrees C. RESULTS: Of 119 patients, 40% achieved a Tmax tumor temperature of > 42 degrees C and 40% achieved 40-42 degrees C Tmax. Higher Tmax) tumor temperatures were observed as tumor size increased. Tumors > 10 cm in largest diameter had a Tmax of 42.2 degrees C. Tumor depth was not a significant factor for the tumor temperatures achieved. Of 119 patients, 11% achieved complete response and 38% achieved partial response. Of the no-response patients, 34% had symptomatic palliation and 15% had stable disease for at least 12 months after treatment. We were able to treat tumors of patients with subcutaneous fat as thick as 3 cm by precooling the fat for 20 min with 10-15 degrees C saline-filled boluses prior to the initiation of heating. During treatment, 60% of patients complained of varying degrees of pain and 19% had pain that was a factor in limiting treatment. Vital signs were relatively stable and not a factor in limiting treatment. CONCLUSION: The Thermotron RF-8 is a useful hyperthermia device that can raise tumor temperatures to a therapeutic level (i.e., 42 degrees C) in a significant proportion of patients with superficial, subsurface, and deep-seated tumors, with minimal adverse effects, complications, and systemic stress. Further clinical studies using improved thermometry systems are warranted.

Adenocarcinoma↗
PubMed1995

Killing of hypoxic cells by lowering the intracellular pH in combination with hyperthermia.

The acidic intracellular environment or low intracellular pH (pHi) increases the thermosensitivity of mammalian cells. The cells in a hypoxic environment produce a greater amount of acidic metabolites than those in an oxygenated environment. However, the hypoxic cells are not more thermosensitive than oxygenated cells since the decrease in pHi is minimized by the mechanisms that regulate the pHi such as Na+/H+ antiport. We hypothesized, therefore, that blocking the regulation of pHi might greatly reduce the pHi and increase the thermosensitivity of hypoxic cells. We tested our hypothesis by heating SCK tumor cells under oxygenated and hypoxic conditions in pH 7.5 or 6.6 medium with or without amiloride, an inhibitor of Na+/H+ antiport. We observed that amiloride increased the thermosensitivity of hypoxic cells markedly. Such a thermosensitization of hypoxic cells by amiloride was more pronounced in an acidic environment, with an enhancement ratio of 1.5, than in a neutral environment, with an enhancement ratio of 1.5. We concluded that lowering the pHi by blocking the regulation of pHi in combination with hyperthermia may be a useful way to eliminate the radioresistant hypoxic cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Thermosensitization by increasing intracellular acidity with amiloride and its analogs.

PURPOSE: The major mechanisms that regulate the intracellular acidity of pHi in mammalian cells are the Na+/H+ exchange and HCO3-/Cl- exchange through the plasma membrane. The purpose of this study was to investigate the feasibility of increasing the thermosensitivity of tumors by increasing intracellular acidity with the use of drugs that inhibit the pHi regulatory mechanisms. METHODS AND MATERIALS: The pHi of SCK tumor cells in vitro was determined with the fluorescence spectroscopy method. The thermosensitizing effects of the drugs on the cells in neutral (pH 7.2-7.5) and acidic (pH 6.6) media were determined by clonogenic assay. The thermosensitization of SCK tumors in vivo by the drugs was determined with the tumor growth delay and the in vivo-in vitro assay for clonogenic cells. RESULTS: The pHi of SCK tumor cells in pH 7.2-7.5 media was similar to the media pH, while the pHi of the cells in pH 6.6 media was about 7.0. The pHi declined and the thermosensitivity of the tumor cells increased when the Na+/H+ exchange was inhibited with amiloride (3,5 diamino-6-chloro-N-(diaminomethylene) pyrazinecarboxamide) and its analogs, HMA (3-amino-6-chloro-5-(1-homopiperidyl)-N-(diaminomethylene) pyrazinecarboxamide) or EIPA (3-amino-6-chloro-5-(N-ethyl-N-isopropylamino)-N-diaminomethylene) pyrazinecarboxamide), especially in acidic medium. The potencies of HMA and EIPA to decrease the pHi and increase the thermosensitivity in vitro were more than 50 times greater than that of amiloride. DIDS (4,4-diiosothiocyanatostilbene-2,2'-disulfonic acid), an inhibitor of the Na(+)-dependent HCO3-/Cl- exchange, exerted little effect on the pHi and thermosensitivity of SCK cells in vitro, but it enhanced the effects of amiloride and its analogs. Amiloride and HMA also significantly enhanced the thermal effect on tumors in vivo, as judged by the tumor growth delay and also by the in vitro-in vivo assay for clonogenic cells. Combinations of DIDS with amiloride or HMA were more effective than either of them alone in increasing the thermal damage in vivo. As in vitro, HMA was far more potent than amiloride in increasing the thermosensitivity of tumor cells in vivo. However, EIPA was not effective in vivo, probably due to a rapid metabolic breakdown of the drug. CONCLUSION: The drugs that interfere with the pHi regulatory mechanism significantly thermosensitized the tumor cells in vitro, particularly those in acidic media. The drugs were also effective in increasing the thermosensitivity of tumors. Because the interstitial environment in tumors is acidic relative to that in normal tissues, the thermosensitization by the drugs may be greater in tumors than that in normal tissues.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Effects of HMA, an analog of amiloride, on the thermosensitivity of tumors in vivo.

PURPOSE: The effects of HMA (3-amino-6-chloro-5-(1-homopiperidyl)-N- (diaminomethylene)pyrazinecarboxamide), an analog of amiloride, on the intracellular pH (pHi) of SCK tumor cells in vitro and on the thermosensitivity of tumors in vivo were investigated. METHODS AND MATERIALS: The pHi of SCK tumor cells in vitro was measured with the BCEC fluorescence spectroscopy method. The effect of HMA on the thermosensitivity of SCK tumors grown SC in the legs of A/J mice was assessed by the tumor growth delay method and the in vivo-in vitro excision assay method. RESULTS: The pHi of SCK tumor cells in pH 7.5 and 6.6 medium was about 7.50 and 7.15, respectively. The presence of 10-50 microM of HMA lowered the pHi by 0.1-0.2 pH units both in pH 7.5 and 6.6 medium. Heating at 43 degrees C 120 min lowered the pHi by 0.2 and 0.3 pH units in pH 7.5 and 6.6 medium, respectively. When the cells were heated in the presence of 10-50 microM HMA, a marked decline in pHi occurred and and the decline in pHi resulting from the combination of heat and HMA was more pronounced in pH 6.6 medium than in pH 7.5 medium. Heating the SCK tumors grown SC in the legs of A/J mice at 43.5 degrees C for 1 h resulted in a growth delay of 3.7 days. When the host mice were i.v. injected with 0.1 mg/kg of HMA and the tumors were heated heated 20 min later, the tumor growth was delayed by 8.2 days, which was 4.5 days longer than that by heating alone. Heating the SCK tumor at 42.5 degrees C for 1 h caused a tumor growth delay of 0.9 days. An i.v. injection of 1 mg/kg or 10 mg/kg of HMA prior to heating at 42.5 degrees C for 1 h caused a tumor growth delay 2.1 and 3.1 days longer, respectively, than that by heating alone. Such an enhancement of heat-induced tumor growth delay by HMA was due to increased cell killing, as determined with the in vivo-in vitro excision assay of clonogenic cells in the tumors. CONCLUSION: HMA is a potent thermosensitizer, particularly in an acidic environment. Thermosensitization by HMA may occur preferentially in tumors relative to normal tissues since the intratumor environment is acidic.

Amiloride↗
PubMed1994

Increase in tumor blood flow by pentoxifylline.

PURPOSE: The effect of pentoxifylline (PTX) on the blood flow in experimental rodent tumors was investigated. METHODS AND MATERIALS: When the R3230 AC adenocarcinoma implanted in the leg of Fischer 344 rats grew to about 1 g, the effect of PTX on the blood flow in the tumor and in the skin and muscle was determined with the microsphere method using 85Sr labelled 25 microns diameter microspheres. The SCK mammary carcinoma was induced subcutaneously in the leg or foot of A/J mice and the effect of PTX on the tumors was investigated: the blood perfusion in the leg tumors (7 mm in diameter) was determined with the 86Rb uptake method and that in the foot tumors (5 mm diameter) was determined with the laser Doppler flow (LDF) method. RESULTS: The blood flow in the R3230 AC adenocarcinoma significantly increased when measured 30 min after an IP injection of 50 mg/kg PTX while the blood flow in the normal skin and muscle remained unchanged. The 86Rb uptake in the SCK tumor slightly increased 30 min after an IP injection of 50 mg/kg PTX. The LDF in the SCK tumors grown in the foot began to increase 5-10 min after an injection of 25 mg/kg PTX reaching 1.5-2.0 times in 20-30 min and it returned to the original level at 60 min. CONCLUSION: The results in the present study together with our previous observation that PTX increases the tumor pO2 in rodent tumors strongly suggest that PTX may be useful for increasing the radiosensitivity of human tumors.

Adenocarcinoma↗