Detection of prostate and colon cancer.
Explore the source record for details and available documents.
Colonic Neoplasms↗
Biomedical subjects
S Stern
Publications and source records attributed to S Stern.
A new role for hypoxia in tumor progression: induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs.
Genome rearrangements including gene amplification are frequent properties of tumor cells, but how they are related to the tumor microenvironment is unknown. Here, we report direct evidence for a causal relationship between hypoxia, induction of fragile sites, and gene amplification. Recently, we showed that breaks at fragile sites initiate intrachromosomal amplification. We demonstrate here that hypoxia is a potent fragile site inducer and that, like fragile sites inducing drugs, it drives fusion of double minutes (DMs) and their targeted reintegration into chromosomal fragile sites, generating homogeneously staining regions (HSRs). This pathway operates efficiently for DMs bearing different sequences, suggesting a model of hypoxia-driven formation of the HSRs containing nonsyntenic sequences frequently observed in solid tumors.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
High-dose etoposide with granulocyte colony-stimulating factor for mobilization of peripheral blood progenitor cells: efficacy and toxicity at three dose levels.
High-dose etoposide (2.0-2.4 g m(-2)) with granulocyte colony-stimulating factor (G-CSF) is an effective strategy to mobilize peripheral blood progenitor cells (PBPCs), although in some patients this is associated with significant toxicity. Sixty-three patients with malignancy were enrolled into this non-randomized sequential study. The majority (55/63, 87%) had received at least two prior regimens of chemotherapy, and seven patients had previously failed to mobilize following high-dose cyclophosphamide with G-CSF. Consecutive patient groups received etoposide at three dose levels [2.0 g m(-2) (n = 22), 1.8 g m(-2) (n = 20) and 1.6 g m(-2) (n = 21)] followed by daily G-CSF. Subsequent leukaphereses were assayed for CD34+ cell content, with a target total collection of 2.0 x 10(6) CD34+ cells kg(-1). Toxicity was assessed by the development of significant mucositis, the requirement for parenteral antibiotics or blood component support and rehospitalization incidence. Ten patients (16%) had less than the minimum target yield collected. Median collections in the three groups were 4.7 (2 g m(-2)), 5.7 (1.8 g m(-2)) and 6.5 (1.6 g m(-2)) x 10(6) CD34+ cells kg(-1). Five of the seven patients who had previously failed cyclophosphamide mobilization achieved more than the target yield. Rehospitalization incidence was significantly lower in patients receiving 1.6 g m(-2) etoposide than in those receiving 2.0 g m(-2) (P = 0.03). These data suggest that high-dose etoposide with G-CSF is an efficient mobilization regimen in the majority of heavily pretreated patients, including those who have previously failed on high-dose cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m(-2) appears to be as effective as higher doses but less toxic.
Acute Disease↗
Fluid replacement for hypotensive injury victims: how, when and what risks?
Intravenous fluid administration is considered universally indicated for patients with post-traumatic hypotension of presumed hemorrhagic origin, regardless of the mechanism of injury, anatomic location, and whether hemostasis has been achieved. This premise is based primarily on animal studies in which blood loss results from a controlled catheter withdrawal. However, more recent hemorrhage models that incorporate a vascular injury, as well as recently completed clinical trials, have indicated that attempts to restore blood pressure before surgical hemostasis may have the undesirable effects of accentuating hemorrhage and mortality.
Journal Article↗
60 Hz electric fields and incandescent light as aversive stimuli controlling the behavior of rats responding under concurrent schedules of reinforcement.
Several reports have shown that animals will sometimes engage in behaviors that reduce their exposure to a 60 Hz electric field (E-field). The field, therefore, can function as an aversive stimulus. In other studies, the E-field at equivalent strengths failed to function as an aversive stimulus. The present experiment, using rats, demonstrates how factors other than field strength can influence whether a subject engages in behavior that reduces field exposure. The general design consisted of giving the rat a choice between two alternatives, one of which sometimes included an added stimulus. Each subject was trained to press each of two levers to obtain food. Pressing one lever was reinforced intermittently under a variable interval 2 min schedule (VI 2); pressing the other lever was reinforced by a second VI 2 schedule operating independently of the first. Under this concurrent schedule the rat spent 50% of the daily 50 min session responding to each of the levers, indicating that they were equally "valued." Next, while the schedules remained in effect, the first response to one of the levers turned on a 100 kV/m E-field which remained on until the rat pressed the other lever. The time spent responding under the schedule associated with the field was reduced by about 5-10%. When the procedure was changed so that no lever presses produced food, i.e., extinction, but the added stimulus contingency remained, the rats spent even less time in the presence of the field. Similar outcomes were observed during both the concurrent food or extinction schedules when incandescent light was used. Thus, both an E-field and incandescent light functioned as aversive stimuli, but the magnitude of the aversiveness was small. Aversiveness depended not only on stimulus intensity, but also on behavioral factors.
Animals↗
Relation of coronary artery disease to atherosclerotic disease in the aorta, carotid, and femoral arteries evaluated by ultrasound.
This prospective study was conducted to correlate the presence of angiographically significant coronary artery disease (CAD) and atherosclerotic disease in the aorta, carotid, and femoral arteries as measured by ultrasound. One hundred two consecutive patients admitted for coronary angiography for suspected CAD participated in the study. All patients underwent transesophageal echocardiography for the evaluation of thoracic aortic atherosclerosis and B-mode ultrasound for evaluation of carotid and femoral atherosclerosis. Intimal-medial thickness > 1 mm in the thoracic aorta or peripheral vessels was considered as evidence of atherosclerosis. Patients with CAD (n = 64) had a significantly higher incidence of atherosclerotic plaques in the thoracic aorta, carotid, and femoral arteries than subjects with normal coronary arteries: 91%, 72%, 77% vs 31%, 47% and 42%, respectively. Extracoronary plaque was a stronger predictor of CAD than conventional risk factors. Evidence of plaque in patients younger than median age (64 years) had a higher specificity than in patients above median age (77% vs 40%, respectively, p <0.0001). Plaque score of the extracardiac vessels was significantly higher in patients with multivessel CAD than in patients with 1-vessel CAD disease and in subjects with normal coronary arteries (p <0.001). Thus, atherosclerotic plaques in the aortic and femoral arteries and, to a lesser extent, in the carotid arteries are strong predictors of CAD.
Adult↗
Improved outcome of elderly patients (> or = 75 years of age) with acute myocardial infarction from 1981-1983 to 1992-1994 in Israel. The SPRINT and Thrombolytic Survey Groups. Secondary Prevention Reinfarction Israel Nifedipine Trial.
BACKGROUND: The number of elderly patients experiencing acute myocardial infarction (AMI) is growing rapidly, and their hospital mortality rate remains high, although mortality after AMI declined in the 1990s with the introduction of new therapeutic modalities. METHODS AND RESULTS: We compared the management, in-hospital complications, and 30-day and 1-year mortality rates in two cohorts of elderly (> or = 75 years of age) AMI patients in the coronary care units in Israel before and after the reperfusion era. The first cohort of 789 consecutive patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial registry in 1981-1983; the second 366 patients came from two prospective nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981-1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in 1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI], 0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38% (hazard ratio [HR], 0.62; 95% CI, 0.50 to 0.76). In the 1992-1994 cohort, the decline in mortality was most marked in patients reperfused by thrombolysis and/or percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery but was also evident in nonreperfused patients: cumulative 1-year mortality rate was 29% in the former (HR, 0.45; 95% CI, 0.31 to 0.67) and 42% in the latter (HR, 0.60; 95% CI, 0.46 to 0.78). CONCLUSIONS: During the last decade, elderly (> or = 75 years) AMI patients experienced fewer in-hospital complications and lower 30-day and 1-year mortality rates, which declined approximately 30%, most markedly in reperfused patients. The favorable outcome in 1992-1994 was related to changes in patient management. Reperfusion therapy is therefore also advocated in elderly AMI patients, unless specific contraindications are present.
Aged↗
Frequency and distribution of atherosclerotic plaques in the thoracic aorta as determined by transesophageal echocardiography in patients with coronary artery disease.
The frequency, distribution, and severity of thoracic aortic plaques were evaluated by transesophageal echocardiography in 152 consecutive patients undergoing coronary arteriography. Coronary artery disease (CAD) was defined as > or = 50% stenosis of > or = 1 major branch. Atherosclerotic plaques were detected in the aorta in 90 of the 97 patients (93%) with CAD, but in only 12 of the 55 patients (22%) with normal coronary arteries. Atherosclerotic plaques in patients with CAD were found predominantly in the descending aorta (in 93%) and in the aortic arch (in 80%), whereas the ascending aorta was the least involved (in 37%). In the descending aorta, 58% of the plaques were complex (>3 mm thick, ulcerated, mobile, or calcified), and in the aortic arch, 40% of the plaques were so classified. Complex plaques were not found in the ascending aorta. The presence of an atherosclerotic plaque in the descending aorta had a sensitivity and a specificity for the prediction of CAD of 93% and 78%, respectively. In the ascending aorta, the sensitivity was lower (37%) but the specificity was higher (100%). The sensitivity of aortic plaques for the prediction of CAD was high in all age groups. Its specificity in subjects >63 years was lower than in younger subjects: 64% versus 90%, respectively. Multivariate logistic regression analysis showed that aortic plaques were a stronger predictor of CAD than were conventional risk factors.
Adult↗
Intraoperative lymphatic mapping for early-stage melanoma of the head and neck.
BACKGROUND: We previously reported dye-directed intraoperative lymphatic mapping and selective sentinel lymphadenectomy for primary cutaneous melanomas draining to the neck lymph nodes. In this study we determined whether combining the dye with a radiopharmaceutical agent would enhance our rate of sentinel node detection. METHODS: One hundred seventeen patients with primary cutaneous melanomas of the upper chest and head and neck underwent preoperative cutaneous lymphoscintigraphy to confirm lymphatic drainage to neck nodes, followed by intraoperative lymphatic mapping and sentinel lymphadenectomy. In 94 cases, isosulfan blue dye was injected at the primary site; in the remaining 23 cases, a 1:3 mixture of radiopharmaceutical and dye was injected, and a hand-held probe was used to determine the radioactive counts. RESULTS: Preoperative cutaneous lymphoscintigraphy identified 129 drainage basins; 12 patients (10%) had dual-basin drainage. During intraoperative lymphatic mapping and sentinel lymphadenectomy, 183 sentinel nodes were identified and excised from 120 basins (1.5 nodes/basin). The blue dye alone identified sentinel nodes in 93 of 101 basins (92%). The probe identified sentinel nodes in 28 of 28 basins, only one of which failed to reveal blue-staining sentinel nodes; thus, the probe plus dye identified sentinel nodes in 27 of 28 basins (96%). Histopathologic analysis revealed metastasis in sentinel nodes from 11 patients (12%) who underwent sentinel lymphadenectomy with blue dye alone and in 3 patients (13%) who underwent sentinel lymphadenectomy with dye plus probe. There were no same-basin recurrences over a mean follow-up of 46 months (range 1 to 125). CONCLUSIONS: Selective sentinel lymphadenectomy is a highly accurate method of staging the regional nodes in patients with primary tumors of the head and neck. Although we initially demonstrated the utility of this technique with blue dye alone, our results now suggest that the combination of dye and radiopharmaceutical may be a more sensitive method to detect sentinel nodes.
Coloring Agents↗
Human papillomavirus is more prevalent in first trimester spontaneously aborted products of conception compared to elective specimens.
In this study the possible role of human papillomaviruses (HPV) in spontaneous abortions is addressed by assaying for HPV DNA in first trimester spontaneous and electively aborted products of conception materials enriched for chorionic villi. The presence of HPVs was measured by polymerase chain reaction (PCR) amplification and DNA dot blot hybridization using an internal probe. The "broad spectrum" HPV primers were directed to amplify E6/E7 junction sequences, while the probe was of an HPV-16 sequence with significant homology to HPV-6/11. The quantity and quality of isolated DNA was also analyzed and compared by observing the PCR amplification of a cellular sequence from the human beta-globin gene. Fifteen of the 25 spontaneous samples (60%) were found to be positive for HPV E6/E7 sequences. In comparison, only 3 of the 15 elective samples (20%) were positive. This is the first study of HPV in fetal materials to incorporate material from elective abortions as a control group. Although confounding contamination from the cervix and vagina can't be ruled out, these data are significant and strongly suggest that HPVs are elevated in spontaneously aborted products of conception. Furthermore, these results suggest the possibility that HPVs may be etiologic agents of at least some spontaneous abortions.
Abortion, Induced↗
Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and adults.
The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PND 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.
Administration, Inhalation↗
Sociodemographic factors and obesity in preadolescent black and white girls: NHLBI's Growth and Health Study.
The association of sociodemographic and family composition data with obesity was studied in 1213 black and 1166 white girls, ages 9 and 10, enrolled in the National Heart, Lung, and Blood Institute's Growth and Health Study. Obesity was defined as body mass index at or greater than age- and sex-specific 85th percentile as outlined in the Second National Health and Nutrition Examination Survey. The prevalence of obesity was higher for pubertal girls than for prepubertal girls and for girls with older mothers/female guardians. As odds ratio of 1.14 was observed for each 5-year increase in maternal age. Obesity was less common for girls with more siblings; the odds for obesity decreased by 14% for each additional sibling in the household. In blacks, the prevalence of obesity was not related to parental employment or to parental education. In whites, the odds of obesity were higher for girls with no employed parent/guardian in the household and for girls with parents or guardians with lower levels of educational attainment. Examining the associations between sociodemographic factors and risk of childhood obesity provides important clues for understanding racial differences in obesity, a major risk factor for coronary heart disease.
Black or African American↗
Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli Thrombolytic National Survey).
OBJECTIVES: This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infarction in an Israeli nationwide survey. BACKGROUND: Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infarction in smokers than in nonsmokers. This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis, myocardial infarction and death. METHODS: The study cohort comprised 999 consecutive patients with an acute myocardial infarction from a prospective nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel. The prognosis of 367 patients (37%) who were smokers (current smokers and those who smoked up to 1 month before admission) was compared with that of 632 nonsmokers (past smokers or those who never smoked). RESULTS: Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infarction and less frequently patients with a previous infarction or a history of angina, hypertension and diabetes than nonsmokers. Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period. Thrombolytic therapy (49% vs. 40%, p < 0.01) and aspirin (89% vs. 80%, p < 0.001) were administered more frequently in smokers than nonsmokers. The crude 30-day (6.0% vs. 15.7%) and cumulative 6-month (7.9% vs. 21.5%) mortality rates were significantly lower (p < 0.0001 for both) in smokers than nonsmokers, respectively. However, after adjustment for age, baseline characteristics, thrombolytic therapy and invasive coronary procedures, the lower 30-day (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.43 to 1.29, p = 0.30) and 6-month (hazard ratio 0.84, 95% CI 0.54 to 1.30, p = 0.42) mortality rates in smokers and nonsmokers were not significantly different. The model had a power of 0.80 for OR 0.50, with alpha 0.1. CONCLUSIONS: In our nationwide survey, the seemingly better prognosis of smokers early after acute myocardial infarction was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile. Smokers develop acute myocardial infarction a decade earlier than nonsmokers. Efforts to lower the prevalence of smoking should continue.
Aged↗
Exposure to combined static and 60 Hz magnetic fields: failure to replicate a reported behavioral effect.
Two experiments failed to confirm the Thomas, Schrot, and Liboff report that low-intensity magnetic fields disrupted the operant behavior of rats. In their experiment, food-deprived rats were trained to press a lever to obtain food pellets under a multiple fixed-ratio (FR) 30, differential reinforcement of low rate 18-24 s (DRL 18-24) schedule. After baseline training, the rats were exposed to a 30 min treatment in a different chamber prior to behavioral testing. When the treatment consisted of a horizontal 60 Hz magnetic field at 5 x 10(-5) Telsa aligned along the north-south axis combined with a static field that reduced the background to 2.61 x 10(-5) Telsa, the rate of lever pressing in the DRL component of the multiple schedule increased reliably during the immediately following test session. Changes in responding were not observed when the rats were exposed to either the static field or the 60 Hz field independently nor during sham exposures to the fields. In the present experiments, only the combined fields, i.e., those reported to be effective, were studied in rats using the same general behavioral and exposure protocol used by Thomas et al [1986a]. In experiment 1, the 2.61 x 10(-5) Telsa was achieved by reducing the vertical component of the static field. In experiment 2, both the horizontal and the vertical components were altered to match those used by Thomas et al. In both experiments additional magnetic field conditions were also studied to ensure that threshold values were exceeded and, in experiment 2, to address concerns about the role of harmonic frequencies of the 60 Hz field. The baseline performances approximated those of Thomas et al. Performances were compared between exposure, sham-exposure and control sessions. None of the exposure conditions altered any of the behavioral measures. The reasons for failing to replicate the results of Thomas et al. remain unknown.
Animals↗
Perinatal methanol exposure in the rat. I. Blood methanol concentration and neural cell adhesion molecules.
Although the acute toxicity of methanol is well documented, few studies have addressed the consequences of perinatal exposures to the low concentrations that are expected to arise from its proposed use as a component of automobile fuel. This report describes the general research design of a series of studies, the effects of methanol exposures on blood concentrations in dams and neonates, and indices of brain development. Four cohorts of Long-Evans pregnant rats, each cohort consisting of an exposure (n = 12) and a control (n = 12) group, were exposed whole-body to 4500 ppm methanol vapor or air for 6 hr daily beginning on Gestation Day 6. Both dams and pups were then exposed through Postnatal Day 21 (PND 21). Blood methanol concentrations determined by gas chromatography from samples obtained immediately following a 6-hr exposure reached approximately 500-800 micrograms/ml in the dams during gestation and lactation. Average concentrations for pups attained levels about twice those of the dams. Selected offspring from Cohort 4 were exposed for one additional 6-hr session at ages that extended out to PND 52. Regression analyses showed that the blood methanol concentrations of the pups declined until about PND 48, at which time their levels approximated those of their dams. Such pharmacokinetic differences might increase the risks posed to developing organisms. Light-microscopic analysis showed no significant abnormalities in the brains of the methanol-treated animals. However, assays of neural cell adhesion molecules (NCAMs) in brains of pups sacrificed on PND 4 showed staining for both the 140 and the 180 kDa isoforms to be less intense in the cerebellum of exposed animals. NCAM differences were not apparent in animals sacrificed 15 months after their final exposure.
Animals↗
Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model.
BACKGROUND: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival. We tested this hypothesis by monitoring immunologic profiles in 59 patients with melanoma who were receiving MCV after surgical resection of regional lymph node or soft-tissue metastases. METHODS: Blood was drawn before vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the first 6-week interval were calculated. Changes in DTH were calculated as the difference between peak and prevaccine values (delta DTH). RESULTS: At a median follow-up of 75.6 months (range 5-138), univariate analysis assigned prognostic significance to gender (p = 0.046), lymph node involvement (p = 0.024), delta DTH (p = 0.044), mean anti-90-kDa MAA IgG (p = 0.0009), and mean anti-90-kDa MAA IgM (p = 0.0014). In multifactorial analysis, only the three immunologic variables significantly impacted survival (p = 0.046, 0.0005, and 0.0053, respectively). A mathematical model based on delta DTH and mean anti-90-kDa MAA IgG and IgM titers closely approximated the observed individual and overall survival rates. CONCLUSIONS: The correlation between overall survival and initial humoral/cellular immune responses to MCV immunotherapy may be useful in selecting patients most likely to benefit from prolonged adjuvant immunotherapy.
Adolescent↗
Transient perfusion and radiosensitizing effect after nicotinamide, carbogen, and perflubron emulsion administration.
In order to improve the effect of radiation on tumour response, nicotinamide, perflubron emulsion and carbogen were administered which act on both diffusion limited hypoxia and intermittent perfusion limited hypoxia. These treatments were used in different combinations. The maximal radiosensitizing effect was found with the combination of the three treatments. The aim of this study was to use a double staining method (Hoechst 33342 and DiOC7(3) to evaluate the influence of nicotinamide, perflubron emulsion and carbogen on transient perfusion in three tumour cell lines transplanted onto nude mice: one rodent (EMT6), two human (HRT18, a rectal adenocarcinoma; and Na11+, a melanoma). For untreated groups, the percentage of closed and mismatched vessels depended on the tumour cell line. Carbogen alone or carbogen plus perflubron emulsion decreased the number of mismatched and closed vessels only for the two human cell lines. Nicotinamide was effective in decreasing the percentage of mismatched and closed vessels only for the melanoma cell line. The combination of nicotinamide, carbogen and perflubron emulsion was the most effective at decreasing both percentage of mismatched and closed vessels in all three tumours studies. This combination was also the most effective at enhancing the radiation response in all three tumours.
Adenocarcinoma↗
Comparison of two techniques for detecting tumour hypoxia: a fluorescent immunochemical method and an in vitro colony assay.
The aim of this study was to compare the percentage of hypoxic cells obtained with two methods: an in vitro colony assay and a new method based on immunodetection of a marker for hypoxic cells (NITP) which could be used in patients. These studies have been carried out using one rodent tumour EMT6 (a mammary carcinoma) and one human tumour HRT18 (a rectal adenocarcinoma). The hypoxic cell fraction was assessed in control mice and in mice receiving two treatments: 250 mg/kg nicotinamide + carbogen, and 250 mg/kg nicotinamide + carbogen + 4 ml/kg perflubron emulsion. The two treatments increased the radiosensitivity of the two cell lines, nicotinamide plus carbogen plus perflubron emulsion having the greatest radiosensitising effect. For untreated and treated tumours, the percentage of hypoxic cells obtained with the in vitro colony assay were comparable to those obtained with immunodetection using NITP. Whatever the treatment, NITP detection was a convenient test to detect the hypoxic cell fraction in the two solid tumours we have studied.
Adenocarcinoma↗