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Method of predicting development of cerebral metastases in case of lung cancer in women

IPC classes for russian patent Method of predicting development of cerebral metastases in case of lung cancer in women (RU 2439579):
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FIELD: medicine.

SUBSTANCE: in women in tissue of lung malignant tumour after radical surgery in pulmonectomy volume and in intact lung tissue, obtained from ablated from lung section of the same lung, level of progesterone is determined. If it reduces in tumour in 5 times and more relative the level of progesterone in intact lung tissue, development of cerebral lung cancer metastases in women within the term from 3 to 8 months is predicted.

EFFECT: possibility of early prediction of development of cerebral metastases in women with lung cancer, which gives possibility of take adequate preventive therapeutic measures.

2 ex

 

The invention relates to medicine, namely to Oncology, and can be used to detect patients with likelihood of metastasis of lung cancer to the brain and the appointment of adequate treatment.

There is a method of determining the criteria for identifying the likelihood of metastatic brain cancer at various sites (sacon p. g Development of organizational forms of diagnosis of metastatic lesions of the Central nervous system. Abstract of Diss. ... candles. the honey. of Sciences, Rostov-on-don, 2006). The author on the basis of the analysis of clinically established cases of detection of metastases of various cancers in the brain, as well as metastases detected on autopsy, defined General criteria of probability of detection of metastatic lesions of the brain.

Such criteria for lung cancer patients had a long history of less than 1 year, the initial stage of the process, namely T2-3N1-2Mxage 50-70 years, the peripheral shape of the tumor growth, histological type adenocarcinoma, the presence of a paraneoplastic syndrome. However it is noted that the frequency of metastatic CNS lesions in women was 4 times lower than those of men.

However, the present study was conducted with the analysis of the clinical material of patients with already having what I metastases to the brain or autopsy material. The author is not the results of the use of the identified criteria for prediction of the development of metastases in particular women, lung cancer patients. Not included in the risk group and patients with small tumors in the lung, without associated lymph nodes (T2N0).

The method for determination of biochemical markers in serum and cerebrospinal fluid in patients with intracranial tumors, including tumors of glial and metastatic nature (Boyardi A., Munari L. Silvani A., Solero C.L., bombardieri E. Neuron specific enolase (NSE) and Thymidine kinase (TK) as markers in diological fluids of brain tumor patients. // Ital. J. Neurol. Sci - 1990. - 11, N.4. - C.359-366). This method was chosen as a prototype. The authors were examined in 104 patients with diseases of the nervous system, including glial tumors and metastases of various cancers. Detected a significant increase in the activity timedancing in the serum of most patients with tumors of primary and secondary nature. Increased levels timedancing in serum and cerebrospinal fluid indicated the presence of metastatic lesions of the brain.

However, as noted by the authors of the study, the sensitivity of the method was 63%, a specificity of 36%, and it is not possible to consider the analyzed indicator pathogenetically determined and used to forecast the development of metastases in the brain malignant process easy. Researchers, mainly recommend using activity indicator timedancing in serum as a marker of disease recurrence after surgical treatment of patients with intracranial tumors.

The aim of the invention is the possibility of early detection in women, lung cancer patients, metastatic lesions of the brain.

This objective is achieved in that in the tissue of malignant lung tumor after radical surgery in volume pulmonectomy in tissue taken from a remote from the tumor site in the same light, determine the level of progesterone and by reduction in tumor tissue in 5 times or more relative to the intact lung tissue predict the occurrence of cerebral metastases of lung cancer in the period from 3 to 8 months.

The invention of "a method for predicting the development of cerebral metastases in lung cancer in women is new, because it is unknown the level of medicine in the field of forecasting the possibility of developing distant intracranial metastases of malignant process easy.

The novelty of the invention lies in the fact that in tumor tissue to determine the level of progesterone and its reduced more than 5 times predict the likelihood of metastasis of lung cancer to the brain. This method for predicting the Oia is new and gives the opportunity to take timely measures to prevent the development of distant metastasis of a tumor.

In open sources information of Russia, CIS and abroad indications for a similar method for predicting the development of cerebral metastases of lung cancer in women, we have not identified.

The invention is industrially applicable as it can be reproduced and repeated many times in the medical health care institutions.

The method is as follows.

A portion of the tumor tissue of the lung in the amount of 100 mg was ground in a homogenizer with 1 ml of cold saline. The obtained homogenate was centrifuged for 30 min at 18000 rpm Precipitate was discarded, and the supernatant was determined by the level of progesterone radioisotope method using sets "Immunotech a Beckman coulter company. As a control sample (intact lung tissue) used a sample of tissue taken from the distant from the tumor site to the same remote lung.

Immunoradiometric determination of progesterone refers to the competitive analysis. The analyzed samples and calibration samples incubated with progesterone labelled125I in test tubes coated with antibodies. After incubation, remove the liquid contents of the test tubes and measure related activity125I. progesterone Concentration in the samples is determined by interpolation on the calibration curve.

Were IP is ledovyy 20 female patients, were treated in the thoraco-plastic branch of FGU "RNII of gynecology and subjected to surgical treatment regarding Central or peripheral lung cancer T2N0-1M0.

Found that 5 patients from 20 value content of progesterone in the tumor tissue was varied in the range of 35.2±4.1 ng/g of tissue against the metric defined in the intact lung tissue - 258,2±21.5 ng/g tissue, which was accompanied by the development of these patients have metastases to the brain within the next 8 months (from 3 to 8 months).

An example of the application method can serve as a statement of case histories.

Patient B., born in 1942, history No. 15821/H, has been with the Department of thoraco-plastic surgery, FSU RNII and gynecology" 29.07.2008 diagnosed with a tumor in the left lung. When contacting the Institute complained of cough without blood, shortness of breath, weakness.

On the radiograph 29.07.08 detected Central tumor of the upper lobe of the left lung with the transition to the distal section of the main bronchus.

Bronchoscopically 30.07.08: main bronchus in the bottom third on 4/5 blocked exophytic, hilly, dense formation, which comes from the upper lobe bronchus. Cytologically (No. 16865) and histologically (345702-03/08) - squamous cell carcinoma.

07.08.08. the patient underwent an operation in the amount of: left pulmonectomy histological analysis No. 47724-29/08 - moderately-differentiated squamous non-squamous cancer metastases in lymph nodes - no). Intraoperatively, the patient was taken to study samples of lung tissue: from the tumor and from the zone that is located remotely from the tumor (intact tissue). From the obtained samples were prepared 10% homogenates, which determined the level of progesterone radioisotope method using sets "Immunotech a Beckman coulter company. In tumor tissue levels of progesterone was 100 ng/g tissue in the intact tissue - 220 ng/g tissue, i.e. in the tumor rate was only 2.2 times lower than in the unaffected lung tissue.

After 1 year and 2 months the patient alive during the next inspection data for recurrence and metastatic process no. Obtained in the study of progesterone levels in tumor tissue compared with the values in the intact tissue corresponds to the predicted favorable prognosis of the disease.

Patient P., born in 1956, case history No. 25043/H, was admitted to the thoracic Department, FSU RNII and gynecology" 02.12.2008 diagnosed with a tumor in the left lung. Sick since September 2008, was treated at the place of residence for chronic bronchitis with cough without blood, shortness of breath, fever up to 37,2-to 37.9°C.

When bronchoscopic study 04.12.2008 found peribronchial-nodular tumor of the upper lobe of the left lung (resultative No. 73958 - adenocarcinoma). Rentgenograficheski: 28.11.2008 - Central tumor of the upper lobe of the left lung 3.0 cm in diameter and the right upper lobe dense tbc foci (since 2004 without speakers).

09.12.08 produced pulmonectomy left. Assigned to symptomatic therapy. During surgery, the patient was extracted tissue samples from the tumor and contralateral (intact) zone is easy, located away from the tumor tissue. From the obtained samples were prepared 10% homogenates, which determined the level of progesterone radioisotope method using sets "Immunotech a Beckman coulter company. In the study produced the following results: progesterone levels in tumor tissue - 28 ng/g tissue in the intact tissue - 261 ng/g tissue, i.e. in the tumor rate was 9.3 times lower than in the unaffected lung tissue.

After 3 months (11.03.09) the patient had complained of pain in the lumbar spine with paresthesia lower extremities. When radiographic examination revealed metastatic lesions of the spine, recommended an MRI of the brain and of the thoracolumbar spine in which 24.03.09 detected metastatic brain lesion (right temporal lobe) and the thoracic spine.

In this study, the decrease in the value of progesterone in tumor tissue compared to intact the cloth 9.3 times pointed to a possible metastasis of lung cancer to the brain, and after 3 months, the patient is established metastatic brain damage.

Technical and economic efficiency of the method is the ability to timely forecasting of the development of cerebral metastases in women, lung cancer patients, and taking appropriate preventive therapeutic measures.

A method for predicting the development of cerebral metastases in lung cancer in women, including Immunoradiometric research in tissue malignant tumors of the lung, characterized in that tissue malignant lung tumor after radical surgery in volume pulmonectomy in tissue taken from a far distant from the tumor site in the same light, determine the level of progesterone and by reduction in tumor 5 times or more relative to the intact lung tissue, predict the development of metastasis of lung cancer to the brain in the period from 3 to 8 months.

 

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