New prognostic factor of lung cancer are being intensively studied currently. A small number of studies compare the importance of molecular makers with so far known functional and clinical prognostic factors. Purpose of this study was to find out whetherp16(ink4) expression is more superior prognostic factor in survival rates in non-small lung cancer (NSCLC) patients than spirometry tests. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) with IIIB and IVA stage and 80 healthy individuals were included. p16(ink4) was immunohistochemicaly detected on formalin-fixed tissues. We measured s pirometry tests : vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), Tiffeneau index (FEV1/FVC ratio) and forced expiratory flow 25% to 75%. 2-year progression-free survival (PFS) and overall survival (OS) were observed. Low p16(ink4) expression and impared spirometry parameters correlated with worse 2-year survival outcomes, in both adenocarcinoma and squamous carcinoma. In squamous carcinoma p16(ink4) expression was an independent negative prognostic marker. Severe impairments of spirometry tests had similar prognostic value as low p16(ink4) expression in both NSCLC subtypes. In contrast to p16 (ink4) as a negative molecular prognostic factor, spirometry testings are widely achievable and affordable and could be serviceable prognostic marker in NSCLC patients in advanced NSCLC. Further studies including all clinical stages of NSCLC are needed.
AIM To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. METHODS A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. RESULTS The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. CONCLUSION Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2.
Growing body of evidence suggests that molecular markers are an important prognostic marker for non-small lung cancer (NSCLC). Using targeted therapy based on these markers leads to improved outcomes in lung adenocarcinoma. However, progress of targeted therapy in squamous lung cancer is still modest. p16(ink) protein acts as tumor suppressor and vascular endothelial growth factor (VEGF) promotes tumor angiogenesis. Purpose of this study was to evaluate the difference in p16(ink4) and VEGF expression between squamous and adenocarcinoma of the lung; to evaluate the relationship of p16(ink4) and VEGF expression to survival outcomes in NSCLC patients, and the difference of their prognostic values between squamous and adenocarcinoma subtypes. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) and 80 healthy individuals were included. p16(ink4) and VEGF proteins were immunohistochemicaly detected on formalin-fixed tissues. One- and 2-year progression-free survival (PFS) and overall survival (OS) were observed. p16(ink4) expression was significantly lower in squamous type compared to adenocarcinoma. In both squamous and adenocarcinoma, high VEGF expression correlated with worse 1-year PFS and OS, but only with worse 2-year PFS. Low p16(ink4) expression correlated with worse 1- and 2-year PFS, as well as OS, in both NSCLC subtypes. In squamous lung cancer p16(ink4) expression was an independent negative prognostic marker. Our study confirms the difference of p16(ink4) protein expression in squamous and adenocarcinoma of the lung. Besides anti-VEGF therapy, the regulation of p16(ink4) expression could have a therapeutic potential in NSCLC, especially in squamous lung cancer.
Molecular regulatory mechanisms of lung cancer initiation and progression are poorly understood. Role of micro RNA (miRNA) 19a in lung cancer is still controversial, as well. Treatments of non-small-cell lung cancer (NSCLC), particularly of the squamous subtype are limited. However increasing evidence point many molecular markers as potential prognostic and therapeutic tools. Purpose of this study was to evaluate differences in miR-19a, as well as miR-126 and let-7b expression profiles between NSCLC tumor tissue and healthy lung tissue. Also, the purpose was to evaluate the relationship of miR-19a, miR-126 and let-7b expression to survival outcomes in NSCLC patients but to evaluate the differences of their prognostic values between squamous and adenocarcinoma subtypes. 50 non-small lung cancer patients (32 squamous and 18 adenocarcinoma) and 45 healthy individuals were included. miRNA expression was detected by quantitative real-time polymerase chain reaction. Microvascular density was immunohistochemicaly quantified by factor VIII-related antigen. One- and two-years survival outcomes were observed. Expression of anti-angiogenic miR-19a, miR-126 and let-7b were significantly lower in tumour tissue compared to control lung tissue. Low miRNAs expression correlated with worse progression-free survival in both squamous and adenocarcinoma of the lung. Poor overall survivals were associated with low miRNAs expression only in the squamous lung cancer. Besides miR-126 and let-7b, our observations confirm also anti-angiogenic role of miR-19a in NSCLC patients and suggest the potential new target therapy in squamous lung cancer.
Angiogenesis is a critical event in the development, progression, and spread of various human cancers, including lung cancer. Molecular mechanisms that underlie the complex regulation of angiogenic processes are poorly understood. However, an increasing body of evidence indicates miRNAs as important regulators of tumor angiogenesis. Forceps biopsies were collected from tumor tissue, surrounding tissue, and non-tumor tissue from 50 NSCLC patients. Lung tissue samples from individuals with no clinical evidence of a cancerous disease served as controls. Immunohistochemical staining for Factor VIII was used to evaluate microvessel density (MVD). TaqMan® primer-probe sets were used in quantitative real-time RT-PCR reactions to determine expression levels of let-7b, miR-126, miR-9, and miR-19a. We demonstrated significantly higher MVD and decreased expression levels of let-7b and miR-126 in tumor tissue and surrounding tissue in comparison to corresponding non-tumor tissue or lung tissue from the control group. In addition, no differences in MVD and expression levels of both miRNAs between tumor tissue and surrounding tissue from NSCLC patients were observed. Low expression of both miRNAs correlated with high MVD and worse progression-free survival and overall survival. These observations strongly suggest similar molecular alternations within tumor tissue and surrounding tissue that comprise a specific microenvironment. Low expression of let-7b and miR-126 seems to have a possible anti-angiogenic role in lung tumor tissue and significantly correlates with worse survival outcomes for lung cancer patients. Moreover, the regulation of let-7b and miR-126 expression could have therapeutic potential because it could reduce tumor angiogenesis and therefore suppress tumor growth in lung cancer patients.
32 squamous lung carcinoma, 18 lung adenocarcinoma and 45 healthy individuals were included. let-7b and miR-126 expression were detected by real-time RT-PCR. 3 tissues of lung cancer patients (tumor, tumor surroundings and healthy lung tissue) were compared. Expression of anti-angiogenic let-7b and miR-126 were significantly lower in tumor tissue and surroundings compared to both healthy lung tissue of diseased patients and control. There was no difference between tumor and tumor surrounding tissue. High let-7b expression and miR-126 expression were highly associated with both better progression-free and overall survival. High micro-vascular density was negatively associated to let-7b and miR-126 expression and highly associated with poor overcome. Our results confirm a possible role of those two miRNas in lung cancer angiogenesis and suggest the potential new target angiogenic lung cancer therapy.
Objective: The primary goal of this study was to determine the difference of abundance of CD4+, CD8+ and CD56+ bronchoalveolar fluid’s lymphocytes and their subpopulations between cancerous lung and healthy lung from the same patient. Methods: Mini-bronchoalveolar lavage was taken from 55 patients from lung with cancer and healthy lung. After laboratory processing and addition of CD4, CD8, CD27, CD28 and CD56 antibody, the material was analyzed by flow cytometer. Results from lung with cancer were compared to the ones from the healthy lung. The examined patients were the test and the control group at the same time. Results: CD27+28+ forms of CD4+ and CD8+ lymphocytes are more activated in the cancerous lung compared to healthy lung, while the CD27-28- forms are less activated in diseased lung. CD4+ forms of CD56+ lymphocytes are more activated in cancerous lung compared to the health lung, while the CD8+ forms are less activated in diseased lung. Conclusion: Immature helper and cytotoxic T lymphocyte response, as well as regulatory NK and NKT cell response are more activated in cancerous lung compared to the health lung of the same patient.
Lymphangioma is a malformation composed of a mass of dilated lymph vessels typically found in the cervical region in children. Mediastinal lymphangioma is a rare condition and accounts for 0.01% to 4.5% of all mediastinal tumors. Only 4 cases of mediastinal lymphangioma involving the heart and great vessels in adults have been described in the available literature. Extremely rarely, lymphangiomas occur as a generalized lymphangiomatosis. We present a case of a woman who coughed up small amounts of fresh blood during 6 months and showed signs of cardiac failure. Several years previously, the patient underwent surgical removal of cystic lymphangiomas from the left ovary, both fallopian tubes and small intestine. A chest radiograph showed an 8-cm round shadow located in the middle lobe. A computerized tomography (CT) scan of the chest with contrast verified the existence of a cyst in the anterior mediastinum. The radiologist suggested that the cyst could have originated in the pericardium. One small cyst also appeared in the projection of the left cardiophrenic sinus. A CT scan with contrast of the patient’s abdomen showed multiple cystic formations in the liver, spleen, kidneys, and left parapelvic region. A fine-needle biopsy of the mediastinal tumor verified the cystic lymphangioma, which was then completely removed surgically. A pathohistological examination confirmed the existence of cystic lymphangioma. The patient was discharged after a period of recovery.
AIM To determinate the difference of abundance of CD4+, CD8+ and CD56+ bronchoalveolar fluid's lymphocytes and their subpopulations between non- and small cell lung cancer. Also, the differences of abundance of examined lymphocytes were compared between main clinical stages of lung cancer. METHODS Mini-bronchoalveolar lavate was taken from lungs of 55 patients with cancer. After laboratory processing and adding CD3, CD4, CD8, CD27, CD28 and CD56 antibody, the material was analysed by flow cytometer. Results of Mini-BAL for non- and small cell lung cancer were compared, as well as the different clinical stages of the disease. RESULTS Immature and regulatory forms of lymphocytes are more activated, while mature and activated forms are less activated in small cell lung cancer compared to non small type. With an increase of the clinical stage of disease, immunological reaction of T lymphocytes is better expressed because of increasing of abundance of immature and regulatory forms of different subpopulations of lymphocytes. CONCLUSION All components of local CD4+ and CD8+ T lymphocyte, as well as NK and NKT cells response were more activated in lungs with small cell lung cancer, and these reactions were more expressed with an increase in the clinical stage.
Edin Jusufovic1,2, Besim Prnjavorac5,6 , Ermina Iljazovic2, Mitja Kosnik3, dragan Keser1,2 Peter Korosec3, Jugoslav Stahov4, Edin Zukic1, Rifat Sejdinovic5, Ekrem Ajanovic5 Policlinic for Pulmonary diseases, Health Medical Centre Tuzla, Bosnia and Herzegovina1 Medical Faculty, University in Tuzla, Bosnia and Herzegovina2 University Clinic of Respiratory and Allergic diseases Golnik, Slovenia3 Faculty of Science, University in Tuzla, Bosnia and Herzegovina4 department of Internal Medicine, General Hospital Tesanj, Bosnia and Herzegovina5 Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina6
Early detection and treatment of preneoplastic lesions represents an obvious option to reduce morbidity and mortality from lung malignancies. Until now, radiological detection, sputum cytology, and autofluorescence have shown limited effectiveness as screening methods. Novel technologies such as Narrow Band Imaging (NBI) are showing promising results, but new studies are still needed to evaluate their use as screening methods. Together with early detection, adequate methods of lesion treatment, such as argon plasma coagulation, are needed. This case report concerns a 45-year-old man who was referred for bronchoscopy after his annual checkup. Using NBI technology, a preneoplastic lesion was identified, and treated using argon plasma coagulation. Our experience has shown us that both NBI screening and argon plasma coagulation are very promising, easily implemented, methods.
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