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1.
31P magnetic resonance spectroscopy of human colon cancer   总被引:1,自引:0,他引:1  
Phosphatic metabolite profiles of 19 malignant and normal human colon specimens were analyzed by techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy at 202.4 MHz. Thirty-one individual phosphorus-containing intermediates of metabolism were identified and quantified for statistical intergroup comparisons. Elevations in relative concentrations of phosphorylethanolamine, IMP, NADP 2'-P, an uncharacterized resonance at 3.72 delta, glycerol 3-phosphorylcholine, phosphorylated glycans and the nucleoside diphosphosugars were seen in malignant tissues concurrently with reductions in relative concentrations of phosphorylcholine, phosphocreatine (PCr), and ATP. The malignant and normal tissue groups were further characterized and contrasted by computing metabolic indices from spectral data. Significant elevations in phosphomonoesters, glycerolphosphodiesters, the ratio of phosphorylethanolamine/phosphorylcholine, and phosphomonoesters/inorganic orthophosphate were detected in malignant tissues along with significant reductions in the ratios of PCr/inorganic orthophosphate, PCr/ATP, the energy charge of the adenylate system and the tissue energy modulus. These results revealed significant alterations in high energy metabolism, low energy metabolism, and membrane metabolism characteristic of malignant tissues. The reduction in high energy phosphates ATP and PCr was balanced by the net increase in nucleoside diphosphosugar and a shift in equilibrium to metabolism involving low energy phosphomonoesters. The spectral data of the tumors, which were of epithelial origin, demonstrated minor metabolites not previously detected in tissue extract analysis of malignant tissues. Detection of these minor metabolites represents an indirect measurement of phospholipid metabolism in malignant tissues.  相似文献   

2.
Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the Scheffé comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue.  相似文献   

3.
Specific genetic alterations during malignant transformation may induce the synthesis and breakdown of choline phospholipids, mediating transduction of mitogenic signals. The high level of water-soluble choline metabolites in cancerous breast tumors, relative to benign lesions and normal breast tissue, has been used as a diagnostic marker of malignancy. To unravel the biochemical pathways underlying this phenomenon, we used tracer kinetics and 13C and 31P magnetic resonance spectroscopy to compare choline transport, routing, and metabolism to phospholipids in primary cultures of human mammary epithelial cells and in MCF7 human breast cancer cells. The rate of choline transport under physiological choline concentrations was 2-fold higher in the cancer cells. The phosphorylation of choline to phosphocholine and oxidation of choline to betaine yielded 10-fold higher levels of these metabolites in the cancer cells. However, additional incorporation of choline to phosphatidylcholine was similar in both cell types. Thus, enhanced choline transport and augmented synthesis of phosphocholine and betaine are dominant pathways responsible for the elevated presence of choline metabolites in cancerous breast tumors. Uniquely, reduced levels and synthesis of a choline-ether-phospholipid may also serve as a metabolic marker of breast cancer.  相似文献   

4.
Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (>70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy.  相似文献   

5.
The activities of enzymes which synthesize and metabolize catecholestrogens were studied in biopsy samples of human breast neoplasms. Estrogen 2-hydroxylase, a cytochrome P-450-dependent enzyme, was present in both benign and malignant neoplasms but not in normal breast tissue. Catechol O-methyltransferase activity was present in all samples examined and was significantly higher in malignant tumors [549 +/- 31 (S.E.) pmol/20 min/mg protein] than in benign neoplasms (226 +/- 41 pmol/20 min/mg protein) or in normal breast tissue (133 +/- 28 pmol/20 min/mg protein). There was no correlation, however, between estrogen 2-hydroxylase and catechol O-methyltransferase activities. The enzymes responsible for the synthesis and metabolism of catecholestrogens are present in some breast tumor specimens, suggesting that in such tissues these metabolites may be formed in vivo.  相似文献   

6.
Glunde K  Jie C  Bhujwalla ZM 《Cancer research》2004,64(12):4270-4276
Proton magnetic resonance spectroscopy ((1)H MRS) consistently detects significant differences in choline phospholipid metabolites of malignant versus benign breast lesions. It is critically important to understand the molecular causes underlying these metabolic differences, because this may identify novel targets for attack in cancer cells. In this study, differences in choline membrane metabolism were characterized in breast cancer cells and normal human mammary epithelial cells (HMECs) labeled with [1,2-(13)C]choline, using (1)H and (13)C magnetic resonance spectroscopy. Metabolic fluxes between membrane and water-soluble pool of choline-containing metabolites were assessed by exposing cells to [1,2-(13)C]choline for long and short periods of time to distinguish between catabolic and anabolic pathways in choline metabolism. Gene expression analysis using microarrays was performed to understand the molecular mechanisms underlying these changes. Breast cancer cells exhibited increased phosphocholine (PC; P < 0.001), total choline-containing metabolites (P < 0.01), and significantly decreased glycerophosphocholine (P < 0.05) compared with normal HMECs. Decreased (13)C-enrichment was detected in choline (P < 0.001) and phosphocholine (P < 0.05, P < 0.001) of breast cancer cells compared with HMECs, indicating a higher metabolic flux from membrane phosphatidylcholine to choline and phosphocholine in breast cancer cells. Choline kinase and phospholipase C were significantly overexpressed, and lysophospholipase 1, phospholipase A2, and phospholipase D were significantly underexpressed, in breast cancer cells compared with HMECs. The magnetic resonance spectroscopy data indicated that elevated phosphocholine in breast cancer cells was primarily attributable to increased choline kinase activity and increased catabolism mediated by increased phospholipase C activity. These observations were consistent with the overexpression of choline kinase and phospholipase C detected in the microarray analyses.  相似文献   

7.
A Barzilai  A Horowitz  A Geier  H Degani 《Cancer》1991,67(11):2919-2925
Phosphorous 31 (31P) nuclear magnetic resonance (NMR) spectra were recorded from perchloric acid extracts of benign and malignant breast tumors. The spectra were correlated with the histopathologic diagnosis and the steroid receptor status of the tumor. Higher relative content of the lipid-derived metabolite glycerolphosphoethanolamine (GPE), the high-energy nucleoside phosphates (nucleoside-diphosphate [NDP], nucleoside-triphosphate [NTP]), and sugar esters of uridine diphosphate (UDPS) appeared in the carcinomas. Malignant tumors also showed a lower ratio of phosphoethanolamine to phosphocholine (PE/PC) than benign conditions. Lower content of the lipid-derived metabolite glycerolphosphocholine (GPC) and high content of the high-energy compound phosphocreatine (PCr) were associated with malignant tumors having high content of estrogen receptors (ER). High PCr content was also associated in the carcinomas with high progesterone receptors (PgR) content. In the benign tumors NDP and NTP were higher in tumors with high PgR content. The authors suggest that 31P magnetic resonance spectroscopy (MRS) of the breast can provide additional variables to diagnose malignancy, and when combined with magnetic resonance imaging (MRI), invasive procedures may be avoided. It also seems that levels of PCr and GPC obtained from the spectra can serve as markers to hormonal receptor status of breast carcinomas, and may be used in addition to the ER and PgR content to improve prediction of the response to hormonal therapy. Additional development requires in situ MRI and MRS combined studies.  相似文献   

8.
Malignant, benign, and normal breast tissues corrected for fat appeared to have similar nuclear magnetic proton spin-lattice relaxation times, contrary to previously published reports. However, due to a lower fat content, benign and malignant tumors relaxed more slowly than the surrounding normal tissue. This provides a possibility for locating them (but not for discriminating between them) in a breast by the nuclear magnetic resonance imaging technique zeugmatography.  相似文献   

9.
Ribonucleotide reductase (RNR) consists of two non-identical subunits, R1 and R2 and is one of the key enzymes involved in DNA biosynthesis. RNR activity is considerably higher in malignant tumors than in normal tissues in the rat suggesting that RNR may play an important role in the pathogenesis of human tumors. In order to obtain immunological reagents to study the localization and level of expression of RNR in various human tissues, a synthetic peptide containing sequences corresponding to the COOH-terminal region of the human R2 subunit was used to generate rat monoclonal antibodies. The generated rat monoclonal antibodies (IgG) inhibited RNR enzymatic activity purified from murine P388 leukemia cells. These antibodies were used to immunohistochemically examine the distribution of RNR in a small panel of 8 malignant and 4 benign human breast tumors. Positive immunostaining for RNR was observed in the cytoplasm of human breast carcinoma cells in which a specific 44 kDa specific band of R2 subunit was also detected by Western blot analysis. The immunostaining was blocked by preabsorption of the antibody with an excess amount of the synthetic peptide immunogen. In 8 of 8 breast carcinomas, positive immunostaining for the R2 subunit was observed whereas noninvolved, adjacent breast tissue showed no staining with this antibody. In addition, few of the benign breast lesions exhibited staining with this antibody. These data indicate that these antibodies can immunohistochemically detect RNR in frozen or formalin-fixed, paraffin- embedded tissues and that there is a differential expression of RNR between breast tumors and non-involved breast tissue. Immunohistochemical detection of RNR using these antibodies may therefore be useful for the diagnosis of human breast tumors.  相似文献   

10.
Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data.  相似文献   

11.
Biochemical markers improve the classification and staging of breast cancer and may refine management decisions if it can be shown that they correlate with accepted prognostic factors or patient outcome. Using phosphorus-31 magnetic resonance spectroscopy ((31)P MRS), we determined the phospholipid content of 43 malignant breast tumors, correlating the profiles with specific histopathologic and clinical features and hormone receptor status. Among the 14 phospholipids identified, the mean mole percentage of sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, and alkylacylphosphatidylcholine predicted cellular infiltration, infiltration type, elastosis, lymphatic invasion, perineural invasion, necrosis, and estrogen receptor positivity. (31)P MRS phospholipid profile data provide statistical correlations among histologic features and molecules known to play important roles in cellular communication, regulation, and processes unique to malignant tissues.  相似文献   

12.
目的:探讨剪切波弹性成像技术定量评估肿块周围组织硬度在乳腺良恶性肿瘤诊断中的应用价值。 方法:收集2019年7月至2022年6月,在我院经手术病理结果证实的乳腺肿瘤患者141例,共152 个肿块,良性肿块66个,恶性肿块86个,进行BI-RADS 分类并测量肿块及周围1 mm、2 mm、3 mm范围组织弹性模量值(Emax、Emean、Esd、Emin、SEmax1、SEmean1、SEsd1、SEmin1、SEmax2、SEmean2、SEsd2、SEmin2、SEmax3、SEmean3、SEsd3、SEmin3),比较良恶性肿块及其周围组织这16组参数之间的差异。 以病理诊断为金标准,绘制受试者工作特征曲线(ROC),比较各参数的曲线下面积(AUC),获得诊断价值最大的参数。结果:乳腺良恶性肿块及其周围组织弹性模量值差异均具有统计学意义,Emax、Emean、Esd值恶性肿块高于良性,Emin恶性肿块低于良性;Emax、SEmax1、SEmax2、SEmax3,4组参数的AUC值均大于0.90,其中SEmax2的AUC值最大,为0.958,诊断截断值为>128.33 kPa,诊断的敏感性77.9%,特异性85.0%,准确率85.5%。 结论:乳腺良恶性肿块周围2 mm范围组织的SEmax2值诊断效能最高,诊断的敏感性、特异性、准确率均优于二维超声,有良好的临床应用价值。  相似文献   

13.
BACKGROUND: The hypothesis that physiological and biochemical changes associated with proliferating malignant tumors may cause an increase in total tissue sodium concentration (TSC) was tested with non-invasive, quantitative sodium ((23)Na) magnetic resonance imaging (MRI) in patients with benign and malignant breast tumors. METHODS: (23)Na and (1)H MRI of the breast was performed on 22 women with suspicious breast lesions (> or =1 cm) at 1.5 Tesla. A commercial proton ((1)H) phased array breast coil and custom solenoidal (23)Na coil were used to acquire (1)H and (23)Na images during the same MRI examination. Quantitative 3-dimensional (23)Na projection imaging was implemented with negligible signal loss from MRI relaxation, or from radio-frequency field inhomogeneity, in less than 15 min. Co-registered (1)H and (23)Na images permitted quantification of TSC in normal and suspicious tissues on the basis of (1)H MRI contrast enhancement and anatomy, with histology confirmed by biopsy. RESULTS: Sodium concentrations were consistently elevated in (N = 19) histologically proven malignant breast lesions by an average of 63% compared to glandular tissue. The increase in sodium concentration in malignant tissue was highly significant compared to unaffected glandular tissue (P < 0.0001, paired t-test), adipose tissue, and TSC in three patients with benign lesions. CONCLUSION: Elevated TSC in breast lesions measured by non-invasive (23)Na MRI appears to be a cellular-level indicator associated with malignancy. This method may have potential to improve the specificity of breast MRI with only a modest increase in scan time per patient.  相似文献   

14.
An emerging clinical modality called proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with 1H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. 1H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast 1H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of 1H-MRS for breast cancer.  相似文献   

15.
Magnetic resonance spectroscopy in clinical oncology   总被引:3,自引:0,他引:3  
Golder W 《Onkologie》2004,27(3):304-309
The combination of magnetic resonance spectroscopy (MRS) and imaging (MRI) has led to mapping metabolites from normal and neoplastic tissue within the time limits of a routine study. MRSI (magnetic resonance spectroscopy imaging) detects metabolites that contain protons, phosphorus, fluorine, or other nuclei. The uniqueness of the information available in vivo and in a non-invasive manner encouraged radiologists and oncologists to apply MRSI in research and clinical practice. Both (1)H- and (31)P-MRS have revealed significant disturbances in amino acids, lipids, and phosphorus-containing metabolites within tumors. Phosphocreatine is often diminished in neoplasms compared to their primary host or surrounding tissues. However, the reduction of the compound does not appear to be closely correlated to the degree of malignancy. Moreover, abnormalities in (31)P spectra from neoplasms are shared by other disorders. Changes in high-energy phosphate levels almost invariably occur with radio- and chemotherapy of tumors. The spectroscopic alterations are often seen before any variations in tumor size and shape can be detected. However, opposite responses can be associated with the same clinical outcome. (1)H-MRS has been successfully used to quantify the extent of neuronal cell loss imposed on the brain during radiotherapy. Recently, MRSI was successfully integrated into radiotherapy planning in prostate cancer patients. (19)F-MRS opens access to artificially induced fluorocompounds such as 5-fluorouracil and its metabolites.  相似文献   

16.
We have used diffusion-weighted proton magnetic resonance spectroscopy (DWMRS) to noninvasively selectively observe only the intracellular metabolites of breast cancer and melanoma cell lines in vitro in real time. Breast cancer cell lines representing different stages in breast cancer progression were chosen for study. Intracellular biochemical profiles of six cell lines perfused in alginate beads were obtained. Spectral differences between groups of cell lines, including choline, lactate, and threonine peaks, were investigated. We also monitored response to the antineoplastic agent, lonidamine (LND), as a function of time and drug concentration in perfused cancer cells. Previous studies reported that this drug induced intracellular acidification and lactate accumulation. Diffusion weighted proton spectra demonstrated a 2- to 9-fold increase in the intracellular lactate signal as a response to LND treatment in several cancer cell lines. These results are consistent with the hypothesis that the principal mechanism of LND in some cancer cells is marked inhibition of lactate transport. Moreover, we have shown that there is a factor of two to three between the response of melanoma cells and that of some types of breast cancer cells. The higher sensitivity of the melanoma cells, as predicted by proton DWMRS, was correlated with changes in water-suppressed magnetic resonance spectra and confirmed by a biological assay. This study demonstrates the feasibility of using DWMRS for monitoring intracellular metabolism and for studying the effects and mechanisms of action of anticancer drugs. We believe that this method can be used for noninvasive clinical applications, such as the differentiation between benign and malignant tissue, real-time monitoring of response to therapy, dose response, and toxicity effects.  相似文献   

17.
Breast metastases in cases of leukemia are rare. We aimed to report the conventional-advanced magnetic resonance imaging (MRI) findings of unilateral breast involvement of acute lymphoblastic leukemia (ALL) and review the literature. A 32-year-old woman was first diagnosed with ALL in treated in 2004. She did not continue the follow-up after 2008. She was presented with a giant, progressive right breast palpable mass in 2010. Mass, contralateral breast tissue were evaluated with MRI, diffusion weighted imaging and MR spectroscopy. With MRI findings, lesion was evaluated as malignant, tru-cut biopsy revealed recurrence of ALL. Lymphoma, malignant melanoma, rhabdomyosarcoma are most common tumors metastase to breast. Breast metastases of leukemia are rare and occur primarily in patients with acute myeloid leukemia. Secondary ALL breast involvement is uncommon. In a patient with malignancy, any enlarging breast mass, even with benign radiologic appearance, should be investigated carefully and metastasis should not be forgotten.  相似文献   

18.
Proton magnetic resonance spectroscopy ((1)H MRS) of the breast has been proposed as an adjunct to the magnetic resonance imaging (MRI) examination to improve the specificity of distinguishing malignant breast tumors from benign breast tumors. In this review, we carry out a pooled analysis of the clinical breast (1)H MRS studies undertaken to date to determine the factors that influence the diagnostic performance of this method. In total, five studies of breast (1)H MRS from four independent centers around the world have been published to date. Altogether, 153 tumors were examined, 100 of which were confirmed histologically to be malignant and 53 of which were benign. The lesions presenting a detectable composite choline signal in their corresponding (1)H MR spectra were diagnosed as malignant, whereas the lesions with no choline signal were diagnosed as benign. The sensitivity and specificity of breast (1)H MRS for detecting breast cancer were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to 93%), respectively, and both values could be as high as 92% after technical exclusions. In a subgroup of 20 young women, the sensitivity and the specificity of the method approached 100%. The factors limiting the sensitivity of the examination were mainly technical. The use of the composite choline signal as a marker for malignancy in breast (1)H MRS is a robust method with highly reliable interpretation, because it is based on the appearance of a single peak. The method is likely to provide even better results with technologic advances in breast MRS that lead to the improved detection of the composite choline signal.  相似文献   

19.
目的:研究TMEM119 在正常及乳腺良恶性肿瘤组织中的表达差异,探讨其在乳腺上皮肿瘤鉴别诊断及恶性肿瘤中的临床及预后价值。方法:利用cBioPortal下载TCGA乳腺癌基因表达谱资料及临床相关资料。免疫组化分析 TMEM119在肿瘤组织及正常组织中的表达差异;进一步探讨TMEM119 的表达差异与乳腺癌患者临床病理特征的相关性及其对预后的影响。结果:乳腺癌组织中的TMEM119表达明显高于配对的正常组织及良性肿瘤(P<0.01),TMEM119 表达与肿瘤组织的淋巴结转移、远处转移、病理分期及预后相关(P<0.05)。结论:TMEM119可为良恶性肿瘤鉴别诊断、预测乳腺癌转移及判断预后的有效分子标记物,是影响患者预后的不良因素之一。  相似文献   

20.
Results of the proton magnetic resonance spectroscopy carried out on normal, benign breast disease and locally advanced breast cancer patients are presented. The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering from infiltrating ductal carcinoma are dominated by the water resonance, while the spectra of the unaffected contralateral breast tissue of these patients are mainly dominated by resonance arising from lipids which is similar to the spectra of normal breast tissue obtained from volunteers (controls, n = 16). In addition to the water and lipid peaks, in majority of the patients (approximately 80%) the water suppressed spectra showed a resonance at 3.2 ppm due to choline containing compounds (TCho) before treatment. In patients receiving neoadjuvant chemotherapy, absence/reduction in choline was observed in 89% of the patients. TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%, respectively. Observation of TCho before treatment and its disappearance (or reduction) after treatment may be a useful indicator of response of locally advanced breast cancer to neoadjuvant chemotherapy.  相似文献   

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