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Application of MTDH to preparation or screening of drugs for curing hyperaldosteronism adenomata or adrenal tumors

A technology for adrenal tumors and aldosterone tumors, applied in the fields of medicine and biology, can solve problems such as unexplained

Inactive Publication Date: 2013-12-04
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the above studies have explained the mechanism of aldosterone hypersecretion in primary aldosterone from different aspects, they have not explained the specific reasons for adrenal tissue hyperplasia and adenoma formation, suggesting that the molecular mechanism of the occurrence and development of primary aldosterone and aldosterone tumors still needs further study. A large number of studies, in which the precise mechanism of different phenotypes and prognostic differences in the same disease is a very important question

Method used

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  • Application of MTDH to preparation or screening of drugs for curing hyperaldosteronism adenomata or adrenal tumors
  • Application of MTDH to preparation or screening of drugs for curing hyperaldosteronism adenomata or adrenal tumors
  • Application of MTDH to preparation or screening of drugs for curing hyperaldosteronism adenomata or adrenal tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] 128 patients diagnosed with primary aldosteronism and treated with surgery

[0026] I. Screening object selection criteria:

[0027] (1) JNC (Joint National Committee on the Prevention, Evaluation, and Treetment of High BLood Pressure) hypertension grade 2 (BP>160-179 / 100-109mmHg), grade 3 (BP>180 / 110mmHg);

[0028] (2) Refractory hypertension (combined use of 3 antihypertensive drugs, which must include diuretics, and each antihypertensive drug has reached the conventional therapeutic dose, and the blood pressure is still greater than 140 / 90mmHg);

[0029] (3) Spontaneous or diuretic-induced hypokalemia;

[0030] (4) Adrenal accidental tumor;

[0031] (5) Family history of premature hypertension or premature (less than 40 years old) family history of cerebrovascular accident;

[0032] (6) There are first-degree relatives of hypertensive patients with primary aldehyde.

[0033] II. Diagnosis of Selected Subjects

[0034] Aldosterone / renin (ARR): All subjects stoppe...

Embodiment 2

[0050] Real-time PCR was used to detect the mRNA level of MTDH gene in the adenoma and nodular hyperplasia tissues of patients with primary aldosteronism, and the results were as follows figure 2 .

[0051] The results showed that: compared with normal controls, the mRNA expression of MTDH in adenoma tissue was significantly increased (1.110±0.111vs1.415±0.038, p<0.01), and the expression in nodular hyperplasia tissue was also increased, but the increase rate was lower than that in normal controls. The adenoma tissue was small (1.268±0.041vs1.415±0.038, p<0.01).

[0052] Similarly, the expression level of LDHB mRNA was increased in aldosterone adenoma and nodular hyperplasia, the former was more obvious (2.004±0.069vs1.677±0.096, p<0.01). The expression levels of YAP1 and YWHAZ mRNA also showed a gradual increasing trend in normal controls, nodular hyperplasia and adenoma tissues (YAP1: 1.075±0.098vs1.268±0.056vs1.697±0.092, YWHAZ: 1.096±0.110vs1.088± 0.050vs1.407±0.088), t...

Embodiment 3

[0054] Get the total RNA obtained in Example 1 and carry out microRNA chip analysis

[0055] In the process of microarray detection, we selected 6 cases of primary aldolism adenoma tissue, 6 cases of nodular hyperplasia tissue, and 3 cases of normal adrenal cortex tissue, and the total RNA of each sample was analyzed by μParaflo TMmicroRNA microarray gene expression profiling. The results showed that among the miRNAs whose average signal intensity was greater than 500, there were 30 miRNAs with p<0.01 expression difference in normal adrenal cortex tissue, nodular hyperplasia tissue and adenoma tissue by analysis of variance, among them, in primary aldehyde tissue There were 8 up-regulated miRNAs and 22 down-regulated miRNAs. There were 65 miRNAs with p<0.05 expression difference, among which 39 up-regulated miRNAs and 26 down-regulated miRNAs in primary aldehyde tissues. At the same time, it can be seen that the up-regulation or down-regulation of multiple miRNA expression le...

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Abstract

The invention relates to the field of medicines and biotechnology, particularly to application of MTDH (metadherin) genes. Proliferation of adrenal cortex cancer cell line H295R can be restrained through reducing the expression quantity of MTDH based on the influence of MTDH on proliferation of adrenal cortex cancer cells in the in vitro experimental study; besides, the expression quantity of MTDH in primary hyperaldosteronism adenomata is obviously improved, therefore, the MTDH genes can be used for adjusting and controlling the proliferation of adrenal cortex cancer cells, and can be used in the preparation and screening of drugs for curing adrenocortical carcinoma or kidney cancer.

Description

technical field [0001] The invention relates to the fields of medicine and biotechnology, in particular to the application of the MTDH gene in the preparation and screening of medicines. Background technique [0002] The MTDH gene is the Metadherin gene, also known as astrocyte elevated gene-1 (AEG-1) or Lyric, which was discovered and successfully cloned in 2004. As a transmembrane protein, MTDH exists in the cytoplasm, endoplasmic reticulum, perinuclear and nucleolus. It is highly conserved during evolution and expressed in most tissues of most vertebrates, but not expressed in invertebrates. Since the cDNA of MTDH has multiple transcripts, which can encode different subunits, multiple protein bands can be seen when detected with antibodies, with molecular weights ranging from 75 to 80kDa to 20kDa, some of which are post-translational proteins The modification stage is formed. Because MTDH is rich in lysine and serine residues, its post-translational modification proces...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K49/00A61P35/00
Inventor 宁光何娟王卫庆李小英曹亚南
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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