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Biomedical subjects

M A Tanner

Publications and source records attributed to M A Tanner.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of cytokines tumor necrosis factor alpha and interleukin 1 beta on endotoxin-mediated inhibition of endothelium-derived relaxing factor bioactivity and nitric oxide production in vascular endothelium.

Endotoxemia results in the release of cytokines that exert complex effects on the cardiovascular system. The purpose of this study was to 1) determine if interleukin 1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) elicit the release of endothelium-derived relaxing factor (EDRF) and nitric oxide derived from the constitutive nitric oxide synthase present in vascular endothelium, and 2) determine if these cytokines alter endotoxin-mediated decreases in EDRF bioactivity and nitric oxide production. Cultured bovine aortic endothelial cells were directly exposed to endotoxin, human recombinant TNF alpha, interleukin 1 beta, or a combination of endotoxin and cytokine for 1 h, followed by a second hour without endotoxin. Subsequently, both basal as well as agonist-stimulated (bradykinin) EDRF bioactivity and nitric oxide (NO) content of the effluent were quantitated. In additional experiments, endothelial cells were exposed acutely over a 30-min assay period to either endotoxin alone, cytokine alone, or endotoxin and cytokine. Following the 2-h incubation, endotoxin alone markedly reduced basal EDRF bioactivity and NO production (44 +/- 13% control, 66 +/- 13% control, respectively) and decreased bradykinin-stimulated EDRF bioactivity and NO production (58 +/- 5% control, 55 +/- 4% control, respectively). TNF alpha and IL1 beta did not stimulate EDRF release or NO production either acutely or after prolonged exposure, nor did they alter agonist-stimulated EDRF bioactivity and NO production. Similarly co-incubation of endotoxin with TNF alpha or IL1 beta failed to significantly alter the inhibitory effects of endotoxin on EDRF bioactivity and NO production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effects of native LDL and oxidized LDL on EDRF bioactivity and nitric oxide production in vascular endothelium.

Low-density lipoprotein (LDL) and oxidized low-density lipoprotein (OxyLDL) have previously been shown to inhibit vasorelaxation caused by endothelium-derived relaxing factor (EDRF). The purpose of the present study was to directly determine the effects of LDL and OxyLDL on EDRF bioactivity and nitric oxide (NO) production in vascular endothelium to further understand the mechanism whereby lipoprotein alters vascular reactivity. Cultured bovine aortic endothelial cells were incubated with either LDL or OxyLDL for 1 hour. After washing the cells free of lipoprotein, agonist-stimulated (bradykinin; BK) EDRF bioactivity and NO content of the effluent were quantitated. These results were compared with control cells not exposed to lipoprotein. In a second series of experiments, the effects of LDL and OxyLDL on EDRF-mediated increases in cyclic guanosine monophosphate (cGMP) in a reporter fibroblast cell line were determined. Last, the direct effects of LDL on NO-induced vasodilation of isolated coronary artery rings were determined by using standard in vitro isometric recording methods. LDL and OxyLDL significantly decreased EDRF bioactivity but not NO production by endothelial cells. When expressed as percent relaxation of the biodetector per mole of NO produced, both LDL and OxyLDL resulted in the release of a significantly less-potent vasodilator than that derived from control cells. In the reporter fibroblast experiments, there was no significant difference in the amount of cGMP generated by fibroblasts in response to medium from control and lipoprotein-treated cells. In isolated ring experiments, LDL did not directly alter NO vasorelaxation. We conclude that both LDL and OxyLDL inhibit EDRF-induced vasorelaxation by complex mechanisms other than the direct inhibition of NO synthesis by endothelial cells or extracellular inactivation of EDRF. LDL and OxyLDL may result in the release of a less potent NO-containing relaxing factor by altering the metabolism of an endogenous nitrosovasodilator.

Animals↗
PubMed1993

Fluoride increases net 45Ca uptake by SaOS-2 cells: The effect is phosphate dependent.

Previous in vitro studies have shown that the effect of fluoride to increase avian osteoblast-like cell proliferation was dependent on the phosphate concentration. In vitro studies have further revealed that fluoride could also have direct effects on osteoblast-like cells to increase phosphate uptake and transiently increase cytosolic calcium. The current studies were intended to determine whether fluoride could increase net 45Ca uptake by human osteosarcoma (SaOS-2) cells and, if so, whether those effects would also be phosphate dependent. The results of these studies indicate that fluoride increased net 45Ca uptake by SaOS-2 cells, with biphasic dose and time dependencies. After 30 minutes of exposure, net 45Ca uptake was increased to a greater extent by 50 microM fluoride (217 +/- 16% of control, P < 0.001) than by 200 microM fluoride; and the stimulatory effect of 100 microM fluoride on net 45Ca uptake was greater after 20 minutes (187 +/- 22% of control, P < 0.001) than after 60 minutes (122 +/- 7% of control, P < 0.05). These effects of fluoride to increase net 45Ca uptake were dependent on the phosphate concentration in the medium. Fluoride had no effect on net 45Ca uptake in medium containing 0.4 mM phosphate, but increased net 45Ca uptake in medium containing 1.2 or 2.0 mM phosphate (P < 0.005). As the phosphate concentration was increased, the biphasic fluoride dose-response curve was shifted to a lower range of fluoride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.

PURPOSE: One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance. PATIENTS AND METHODS: Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue. RESULTS: The 3-year actuarial event-free survival (EFS) rate for the 47 HD patients is 49%, with a median followup duration of 2 years. For the 53 NHL patients, the 3-year actuarial EFS rate is 40%, with a median follow-up duration of 19 months. By multivariate analysis, minimal disease on admission (all areas < or = 2 cm) is associated with improved EFS (HD, P = .003, NHL, P = .03). The projected EFS rate for HD patients entering with minimal disease is 70% versus 15% for patients with bulky disease (P = .0001). The projected EFS rate for NHL patients with minimal disease is 48% versus 25% for patients with bulky disease (P = .04). Posttransplant involved-field radiotherapy, administered to 26 of the last 61 patients, was associated with an improved EFS rate for NHL patients (P = .015). The BEAC regimen was well tolerated by patients who entered the study with minimal disease (mortality rate, < 5%), but caused significant toxicity in patients with bulky disease (mortality rate, 25%). CONCLUSION: Disease burden before autotransplantation is an important predictor of regimen-related toxicity and EFS. Posttransplant involved-field radiotherapy may improve outcomes in select patients with NHL. The BEAC regimen is safe and effective, particularly for patients with minimal disease.

Actuarial Analysis↗
PubMed1992

Treatment of relapsed or refractory Hodgkin disease and non-Hodgkin lymphoma with high-dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue.

Nine patients with relapsed or refractory Hodgkin disease or non-Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 x 10(9)/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days posttransplant. Two patients died of transplant-related complications and one relapsed 250 days post-transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution. Although administration of cytotoxic therapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive "salvage" therapy. Additional follow-up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants.

Adult↗
PubMed1992

EDRF and nitric oxide production in cultured endothelial cells: direct inhibition by E. coli endotoxin.

Recent studies have yielded contradictory interpretations about the influence of gram-negative endotoxin on endothelium-derived relaxing factor (EDRF). We tested the hypothesis that Escherichia coli endotoxin exerts primary facilitatory or, alternatively, inhibitory actions on EDRF release and the synthesis of either nitric oxide or a nitroso compound in cultured endothelial cells. Bovine aortic endothelial cells were grown on microcarrier beads and either exposed acutely (30 min) to E. coli endotoxin or incubated with endotoxin for 1 h followed by a 1-h wash (prolonged exposure). EDRF bioactivity was measured under basal, bradykinin-stimulated, and A23187-stimulated conditions using standard isometric tension recordings. EDRF-derived nitric oxide was quantitated using a specific chemiluminescence technique. Endotoxin (0.005-5 micrograms/ml) decreased EDRF bioactivity and nitric oxide production under both basal and bradykinin-stimulated conditions after prolonged, but not acute, exposure. A23187-stimulated EDRF bioactivity and nitric oxide production were minimally, albeit significantly, reduced after endotoxin. The present results demonstrate that EDRF activity and nitric oxide production are decreased in vascular endothelial cells exposed to endotoxin. Endotoxin itself failed to directly stimulate EDRF release from endothelium. Alternative sources of nitrovasodilators, endothelium-independent effects, or release of other vasoactive mediators by endotoxin may be responsible for systemic hypotension during in vivo endotoxemia.

Animals↗
PubMed1991

A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors.

Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Effects of oxygen tension on endothelium dependent responses in canine coronary microvessels.

STUDY OBJECTIVE: The aim was to determine the direct effects of oxygen tension on endothelium dependent vasodilator responses in canine coronary microvessels. DESIGN: Coronary microvessels were isolated and studied in vitro in a no flow constant pressure state using a video dimension analysing system. Microvessels were exposed to different partial pressures of oxygen. Endothelium dependent responses to acetylcholine and A23187 calcium ionophore were obtained with and without indomethacin during hyperoxia and normoxia, and compared to responses during hypoxia. Dose-response curves were also obtained to the direct smooth muscle dilator nitroprusside during normoxia and hypoxia. The reversibility of the effects of hypoxia on the acetylcholine response was studied after return to hyperoxic conditions following hypoxia. EXPERIMENTAL MATERIAL: Coronary microvessels (58-150 micron diameter) were obtained from adult mongrel dogs of either sex. MEASUREMENTS AND MAIN RESULTS: Exposure of preconstricted microvessels to hypoxia alone [PO2 5.8(0.4)kPa] resulted in a 25.9(SEM 6.8)% relaxation that was abolished by indomethacin [0.35(2.9)% relaxation]. Acetylcholine elicited dose dependent vasodilatation, with no significant differences in sensitivity between normoxia [PO2 14.6(0.04) kPa] and hypoxia: EC50 = 0.023 v 0.027 mumol.litre-1, respectively. During hyperoxia [PO2 80.2(6.0) kPa] there was a significant increase in the EC50 value to 0.09 mumol.litre-1 (hypoxia and normoxia v hyperoxia). After inhibition of prostaglandin synthesis with indomethacin, the sensitivity to acetylcholine was significantly decreased during hypoxia (EC50 = 0.16 mumol.litre-1) when compared to normoxia and hyperoxia. Indomethacin alone did not alter the acetylcholine response during normoxia and hyperoxia. As with acetylcholine, the sensitivity of indomethacin treated microvessels to A23187 was also decreased during hypoxia when compared to hyperoxia. There was no difference in the nitroprusside response during hypoxia and hyperoxia. The decreased vasodilator response to acetylcholine after hypoxia was persistent up to 2 h after return to hyperoxic conditions. CONCLUSIONS: Hypoxia decreases vasodilatation due to endothelium dependent relaxing factor, and oxygen tension has an important influence on both receptor dependent and receptor independent endothelium dependent vasodilator responses in coronary microvessels. Hypoxia also induces a prostaglandin mediated dilatation of preconstricted coronary microvessels. The effects of hypoxia on endothelium dependent responses are persistent up to 2 h.

Acetylcholine↗
PubMed1991

Applications of multiple imputation to the analysis of censored regression data.

The first part of the article reviews the Data Augmentation algorithm and presents two approximations to the Data Augmentation algorithm for the analysis of missing-data problems: the Poor Man's Data Augmentation algorithm and the Asymptotic Data Augmentation algorithm. These two algorithms are then implemented in the context of censored regression data to obtain semiparametric methodology. The performances of the censored regression algorithms are examined in a simulation study. It is found, up to the precision of the study, that the bias of both the Poor Man's and Asymptotic Data Augmentation estimators, as well as the Buckley-James estimator, does not appear to differ from zero. However, with regard to mean squared error, over a wide range of settings examined in this simulation study, the two Data Augmentation estimators have a smaller mean squared error than does the Buckley-James estimator. In addition, associated with the two Data Augmentation estimators is a natural device for estimating the standard error of the estimated regression parameters. It is shown how this device can be used to estimate the standard error of either Data Augmentation estimate of any parameter (e.g., the correlation coefficient) associated with the model. In the simulation study, the estimated standard error of the Asymptotic Data Augmentation estimate of the regression parameter is found to be congruent with the Monte Carlo standard deviation of the corresponding parameter estimate. The algorithms are illustrated using the updated Stanford heart transplant data set.

Algorithms↗
PubMed1990

Further analysis of the time factor in squamous cell carcinoma of the tonsillar region.

Recently, Bataini et al. reported that overall time was the major treatment-related determinant of local control in 465 squamous carcinomas of the tonsillar region. They did not, however, quantify the relationship or relate it to the doubling time of tumorigenic cells, except qualitatively. This note reports an attempt at that quantification.

Carcinoma, Squamous Cell↗
PubMed1989

Interactions of thymidine, hyperthermia, and cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) in human T-cell leukemia.

Using JM and MOLT3, two human T-cell acute lymphoblastic leukemia cell lines, we investigated the ability of 24-h thymidine exposures to enhance the cytotoxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin). Clinically achievable thymidine concentrations (for 24 h) significantly enhanced carboplatin killing. Unexpectedly, thymidine-carboplatin enhancement was as great at a relatively low 200-micrograms thymidine/ml as at the clinically much more toxic range of 1000 micrograms/ml. For a constant thymidine concentration (500 micrograms/ml), thymidine-carboplatin interaction increased with longer thymidine exposures until about 16 to 24 h. Thymidine and 41.8 degrees C hyperthermia (for 1 h) together enhanced carboplatin killing significantly more than did hyperthermia-carboplatin or thymidine-carboplatin combinations. These results show that relatively brief, presumptively nonmyelosuppressive thymidine exposures can significantly increase carboplatin killing. Carboplatin-thymidine killing can then be further augmented by 41.8 degrees C hyperthermia.

Antineoplastic Agents↗
PubMed1989

Psychosexual adaptation to breast cancer surgery.

Disturbances associated with a breast cancer diagnosis were defined when psychological assessments from 63 patients with a known breast cancer diagnosis were compared to those from 56 patients with an as yet undiagnosed malignancy. Subsequent assessments from the 56 patients with an undiagnosed breast cancer showed disturbances after they saw a physician compared with the assessments from 72 similar patients ultimately diagnosed as benign. Apprehension apparently arose from clues given before a biopsy was done even though the cancer was not yet diagnosed. Compared with the benign breast disease group, the disturbances in patients suspected or diagnosed with breast cancer were found chiefly in assessments of mood and adjustment, and less in assessments of more durable characteristics of personality, psychopathology, and sexual behavior. Psychological problems associated with breast cancer decreased over time, but residuals persisted for at least 16 months postoperatively. Few differences were found between 41 patients who elected breast-conserving surgery and 78 who were treated with mastectomy. Problems were not eliminated by operations which saved the breast.

Adaptation, Psychological↗
PubMed1989

Fine-needle aspiration for breast mass diagnosis.

Our accuracy in diagnosing 464 solid breast masses by fine-needle aspiration was enhanced by a statistically based algorithm for distinguishing between benign and malignant epithelial cells. Epithelial cells were obtained from 378 breast masses by fine-needle aspiration; nonepithelial cells considered diagnostic of benign conditions were obtained from 66 breast masses, and 19 aspirations were considered unsatisfactory. Excluding one benign cystosarcoma, the algorithm gave 3 false-negative diagnoses and 16 false-positive diagnoses with 211 benign and 167 malignant samples. The overall clinical performance measures for the 444 masses from which diagnostic fine-needle aspirations were obtained and excluding the cystosarcoma were 0.98 sensitivity, 0.94 specificity, and 0.92 positive predictability. Masses diagnosed as benign by fine-needle aspiration can be followed up clinically. Intraoperative frozen section is needed before definitive surgery to determine invasion and confirm the diagnosis of some cytologically malignant masses.

Algorithms↗
PubMed1989

Inhibition of rat mammary carcinogenesis by monoterpenoids.

We have previously demonstrated the cancer chemopreventive activities of the monocyclic unsaturated monoterpene d-limonene. In the present work we report data evaluating the chemopreventive effects of limonene and five other monoterpenes with various chemical structures using a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis model. The terpenes tested include: oxygenated [(-)-menthol] and non-oxygenated (d-limonene) monocyclic forms, oxygenated (1,8-cineole) and non-oxygenated [(+/-)-alpha-pinene] bicyclic forms and oxygenated [(+/-)-linalool] and non-oxygenated (beta-myrcene) acyclic forms. Dietary additions of each of the monocyclic terpenes, d-limonene or (-)-menthol resulted in a significant inhibition of mammary carcinogenesis. Furthermore, menthol was found to be a more potent chemopreventive agent than limonene during the DMBA initiation of rat mammary tumors. The acyclic and bicyclic terpenes had no significant chemopreventive activities at the dose levels used in these studies.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Clonogenic cells and rat mammary cancer: effects of hormones, X rays, and fission neutrons.

On Day 0, young adult female F344 rats were adrenalectomized and intrasplenically implanted with a pituitary gland and capsule containing estrone. All were thereafter given 2.5 mg deoxycorticosterone per week and the choice of saline or tap water. This treatment yields high prolactin levels and glucocorticoid deficiency (Prl+/Glc-). On Day +48, total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X rays on Day +48 increased total mammary carcinomas per rat day at risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X rays on Day -1 yielded tumor latencies and frequencies insignificantly different from unirradiated controls and significantly different from the dose on Day +48. Total carcinomas per rat day at risk were better fit by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10, and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X rays was thus influenced by total clonogen numbers and/or proliferation rates; that of neutrons was not.

Animals↗
PubMed1988

Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin.

The effects of dietary supplementation of flavonol quercetin on both 7,12-dimethylbenz(a)anthracene (DMBA)- and N-nitrosomethylurea-induced mammary cancer in female Sprague-Dawley rats were determined. Quercetin diet was started 1 wk before intragastric instillation of DMBA (65 mg/kg of body weight) or i.v. injection of N-nitrosomethylurea (50 mg/kg of body weight) and was continued during the entire period (20 wk) of the experiment. Dietary quercetin inhibited both the incidence and the number of palpable rat mammary tumors; rats fed on 2% quercetin had 25% less incidence of mammary cancer, while the average number of mammary tumors per rat was reduced by 39% at 20 wk post-DMBA administration compared to animals on a control diet. In a separate experiment, a 5% quercetin diet elicited a greater inhibitory effect on the induction of rat mammary tumors by DMBA than was observed with a 2% quercetin diet. The inhibitory effect of quercetin on mammary tumor incidence in rats on 2% and 5% diets and on tumor multiplicity in animals on a 5% diet was statistically significant (P less than 0.05). In addition, the risk of the development of a palpable tumor (as determined by the nonparametric estimate of the hazard function) in the quercetin-fed group was lower than the group on control diet throughout the course of the experiment. Furthermore, 5% dietary quercetin significantly inhibited (P less than 0.05), although to a lesser extent than observed in DMBA-induced tumor formation, both the incidence and the number of palpable mammary tumors per rat induced by N-nitrosomethylurea. Dietary quercetin did not elicit any detectable sign of toxicity. The gain in body weight in rats on the quercetin diet and the quantity of diet consumed per rat per week were similar to those for rats on the control diet.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Sensitization of nitrosourea-resistant Mer+ human tumor cells to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea by mild (41 degrees C) hyperthermia.

Experiments were designed to determine whether heat treatment could sensitize nitrosourea-resistant human tumor cell lines expressing a repair system (O6-alkylguanine DNA alkyltransferase; Mer+) capable of removing monoadducts from the DNA of treated cells prior to the formation of lethal interstrand cross-links. Effects of temperatures compatible with systemic hyperthermia were of particular interest, and, consequently, the effect of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) exposure in vitro for 4 h at 37 degrees C was compared with that for 1 h at 41 degrees C followed by 3 h at 37 degrees C. CCNU toxicity was significantly enhanced by heat treatment in the Mer+ HT-29 human colon carcinoma, and in HeLa-S3 and HeLa-CCL2 cell lines [thermal enhancement factor (ratio of CCNU doses required to reduce cell survival to 0.001 at 37 degrees C and 41 degrees C) = 1.3-1.4]. Pharmacokinetic studies indicated that the effect of heat treatment on CCNU toxicity was not attributable to exposure to increased concentrations of reactive species, nor was the enhancement due to a direct effect of heat and/or drug on alkyltransferase activity. A similar enhancement of CCNU toxicity was also observed in a Mer- line, HeLa-MR (thermal enhancement factor = 1.3). Heat-sequencing experiments clearly demonstrate that heat and CCNU must be administered concurrently. Alkaline elution experiments were designed to examine DNA-DNA cross-link formation in Mer+ and Mer- cells exposed to CCNU at 37 degrees C and 41 degrees C, but quantitation of cross-link formation was not possible owing to the persistence of single strand breaks in the DNA of drug-treated cells. Nevertheless, collectively the data indicate that thermal enhancement of CCNU toxicity is independent of effects on alkytransferase activity and indicate that hyperthermia could provide an effective strategy for improving the nitrosourea response of resistant Mer+ tumors.

DNA↗