Nuclear localization of aldolase A correlates with cell proliferation.

Muscle fructose 1,6-bisphosphate aldolase (ALDA) is a glycolytic enzyme which may localize both in nuclei and cytoplasm of cells, however its role in the nuclei is unclear. Here, we demonstrate the links between subcellular localization of ALDA and the cell cycle progression as well as the availability of energetic substrates. Results of our studies indicate that nuclear localization of ALDA correlates with the proliferative activity of the cells and with the expression of Ki-67, a marker of proliferation, both in the KLN-205 (mouse lung cancer cells) and human squamous cell lung cancer cells (hSCC). Chemically-induced block of cell cycle entry in S phase and the inhibition of transcription stimulate removal of ALDA from cells nuclei suggesting that nuclear ALDA is involved in cells proliferation. On the other hand, subcellular distribution of the enzyme also depends on the stress and pro-survival signals mediated by the Akt and the p38 pathways and, in non-proliferating cells, on the availability of glucose and lactate. The results presented here point to ALDA as a factor involved in the regulation of cells proliferation.

Association of C-terminal region of phosphoglycerate mutase with glycolytic complex regulates energy production in cancer cells.

Cancer cells prefer anaerobic ATP synthesis, regardless of the availability of oxygen. It has been hypothesized that in these cells, glycolytic enzymes associate into a large complex, which results in an increased efficiency of glycolytic flux. However, there is no convincing in vivo evidence supporting this hypothesis. Here, we show that all the enzymes of triose phosphate metabolism, from aldolase to pyruvate kinase consecutively, form a macromolecular complex in vivo and that disruption of such complex significantly inhibits lactate release and ATP synthesis in the glycolytic pathway. Composition of the complex and the effectiveness of the glycolytic flux depends on lactate and glucose concentration. High concentrations of exogenous lactate reduces association of the C-terminal region phosphoglycerate mutase (PGAM) with the complex which results in its disruption and inhibition of ATP synthesis. Additionally, high lactate affects nuclear localization of PGAM and ceases cell proliferation. Our findings might provide new prospects for cancer treatment using low-molecular weight competitors to destabilize the glycolytic complex and reduce proliferative potential of cancer cells.

Positive correlation between cyclooxygenase 2 and the expression of ABC transporters in non-small cell lung cancer.

BACKGROUND: The primary method of treatment of non-small cell lung cancer (NSCLC) in stage IIIB and IV is chemotherapy. Previous data suggested a correlation between cyclooxygenase-2 (COX-2) expression and the multidrug-resistant phenotype of cancer cells. MATERIALS AND METHODS: In this prospective study, 32 patients with NSCLC in stage IIIB and IV from 1,078 patients were included. The expression of COX-2 as well as the expression of the ABC transporters MDR1/P-glycoprotein (MDR1/P-gp), BCRP and MRP1 were detected immunohistochemically. RESULTS: Univariate and multivariate analyses demonstrated no prognostic or predictive significance of these proteins. It was merely demonstrated that complete or partial response are favourable factors for prediction of longer progression-free survival time. However, a strong positive correlation between the expression of COX-2, MDR1/P-gp and BCRP was found in NSCLC. CONCLUSION: These data suggest no clinical impact for the expression of MDR1/P-gp, MRP1, BCRP or COX-2 in NSCLC, but a putative coregulation of COX-2 and MDRI/P-gp and BCRP in NSCLC.

Causes and management of postpneumonectomy empyemas: our experience.

OBJECTIVE: Infection of the pleural cavity and development of empyema are potential dangers after pneumonectomy. In spite of decrease in frequency of postpneumonectomy empyemas (PPE) formation, this is still a serious complication. The aim of this study was: analysis the mechanisms of postpneumonectomy empyema formation and attempt the elaboration of the optimal management of these patients. METHODS: 1148 pneumonectomies were performed at the Thoracic Surgery Centre between 1984 and 2002. PPE occurred in 76 (6.6%) patients between the ages of 25-77. For statistical purposes the chi2 test was used. RESULTS: The causes of PPE showed that in 56/76 (73.7%) patients its formation was due to a postoperative complications. In 4/76 (5.3%) cases the cause of empyema was associated with intraoperative infection during the operation. In 3/76 (3.9%) patients a long period of treatment at the intensive care unit due to postoperative shock predisposed to the infection. In 13/76 (17.1%) patients the cause was not established. Statistically significant PPE was associated with postoperative complication (P=0). Postoperative complication caused by one factor was more frequent than those caused by 2 or 3 factors (P=0). PPE was the most often diagnosed in the second postoperative week (P=0.0001). 13 (17.1%) patients died during the 30 days after beginning of the treatment of PPE. The course of complication was more impetuous and more deaths were noted in patients diagnosed during the first week after operation. Only 8 patients from 34, who were selected for thoracentesis and lavage with deposition of antibiotics into the pleural cavity recovered. Jointly 68 (89.5%) patients underwent chest tube drainage. After 2-3 weeks the tube was removed in 16 patients. 17 (22.4%) patients were not qualified for operation. 35 (46.1%) patients underwent different operative procedures: 20 fenestrations, 12 fenestrations with myoplasty and 3 thoracoplastic operations with myoplasty. CONCLUSIONS: The most common causes of PPE were postoperative complications, mainly bronchopleural fistula. The scheme of therapeutic management in PPE was elaborated as a result of our experience.

Unusual case of adenomyosis of the uterine body with malignant clinical course.

We report an unusual case of adenomyosis with asymptomatic thoracic endometriosis. A 30-year old woman had a history of nephroblastoma, two missed abortions and one childbirth by caesarean section. The pregnancy was complicated with asymmetric fetus hipotrophy. Two years after delivery she had assessments for dysmenorrhea, dyspareunia, pelvic pain, and anemia. Gynaecological examination and pelvic endovaginal ultrasonography revealed enlarged uterus. Tumour structure was found with diameter ranging from 40 to 63 mm. The round focus with diameter 15 mm in the left lung by chest roentgenogram was revealed. The patient was diagnosed as follows: hysterography, curettage, bronchoscopy, laparoscopy. Hysterectomy without adnexes was performed and tumour of the left lung was resected. Histologic diagnosis revealed adenomyosis of uterine body and parenchymal pulmonary endometriosis. Two years after operations patient alive without sings of disease.

[Mediastinal tumors in children]. / Guzy sródpiersia u dzieci.

Mediastinal tumours are not very common among various tumours in children. The aim of our study was to evaluate the clinical features, diagnostic approaches and surgical management in 125 patients treated in our Department for 30 years. There were 39 lesions in the anterior, 21 in the medial and 49 in the posterior mediastinum. Solid tumours were diagnosed in 78% of patients. The range of age was between 4 days and 18 years of life. Patients below 5 years of life accounted for 68%. The most common were neurogenic tumours--35%, less frequently tumours of lymphatic origin were seen. Complete excision was possible in 66% of patients, in 26% open biopsy examinations were performed. Enlarged thymus was under control in our out-patient clinic. Combined treatment (radio-, chemotherapy and surgical treatment) was introduced to deal with neurogenic tumours in children. Complete remission lasting 3 years was achieved in 71% of patients in this group. Comparing two periods of time (1970-85 v 1986-2000) no significant differences were found in the prevalence of any kind of mediastinal tumours.

[Tumor markers TPA and Cyfra 21.1 in patients with non-small cell lung cancer after surgery and chemotherapy]. / Markery nowotworowe TPA i Cyfra 21.1 u chorych na raka niedrobnokomórkowego pluca po leczeniu chirurgicznym i chemioterapii.

In 27 patients with operable non-small cell lung cancer (NSCLC) submitted to radical surgery followed by 3 cycles of chemotherapy (cht) serum concentrations of Cyfra 21.1 and TPA were studied. The measurements were performed before and 14 days after surgery, before each cht and every 60th day after cht was completed, for 2 years. Seven patients died during the follow up. There was no significant correlation between preoperative cyfra 21.1 and TPA serum concentrations and stage of diseases or histologic types of NSCLC. Initial concentrations of the two markers had no prognostic meaning. A significant decrease of 2 markers was observed after surgery in the whole group and in patients with therapy success. While adjuvant cht did not influence significantly serum concentrations of the markers, we showed a significant elevation of 2 markers about 4 months before death. It seems that establishing of values of Cyfra 21.1 and TPA in the patient's follow up may be useful in recognition of tumour relapse.

[Post-pneumonectomy empyemas: causes, clinical course, management]. / Ropniaki komory poresekcyjnej: przyczyny, przebieg kliniczny, postepowanie.

Between 1984 and 2000 in the Thoracic Surgery Centre pneumonectomies were performed in 947 patients. Postpneumonectomy empyema (PE) occurred in 67 (7%) patients. The aim of this paper were: analysis the reasons of postpneumonectomy empyema appearance, defined bacterial flora, clinical course and optimal management. The causes of PE were: pleural cavity haematoma (20 patients-29.8%), wound suppuration (18 patients-26.8%), bronchial fistula (31 patients-46.2%). These complications appeared singly or together in 49 (73.1%) patients. In 2 (3.0%) patients a long treatment in the Intensive Care Unit because of postoperative shock was the cause of infection. In 3 (4.5%) cases the cause of empyema was associated with infection during the operation. In 13(19.4%) cases the cause of empyema was not established. In 55 patients infections of pleural cavities were diagnosed in the first 8 weeks after operations. In 12 patients empyemas were established later. 12 (17.9%) patients died during the analyzed 1 year period after operation. In 18 (26.9%) patients infections were caused by only one bacterial strain and in 49 (73.1%) by two or three bacterial strains. The different methods of treatment (thoracentesis, drainage, operation) depending on general condition of patient were done.

Treatment of recurrent primary spontaneous pneumothorax - own experience.

UNLABELLED: Primary spontaneous pneumothorax could be a serious therapeutic problem in case of recurrence. Lack of therapeutic standards sometimes leads to delay in definitive surgical treatment and could cause respiratory complications. The aim of the study was the evaluation of treatment results in patients with recurrence of primary spontaneous pneumothorax and looking for optimal therapeutic method after first recurrence (surgical treatment vs. pleural drainage). MATERIAL AND METHODS: Between 01.01.2009 and 31.07.2010 fifty four patients with recurrent primary spontaneous pneumothorax was hospitalized in Wroclaw Thoracic Surgery Centre (24.3% of all patients with pneumothorax). The recurrence was treated surgically in 24 cases, in 30 pleural drainage was performed: simple drainage (n=14) or drainage with chemical pleurodesis (n=16). Mean age of patients treated without surgery was higher than surgically treated (p=0,012). RESULTS: In surgery group no recurrence was found, in drainage group 11 recurrences occurred (p=0.0009). In group of 11 patients with second recurrence, pleurodesis was performed four times (36%) vs. 12 times (63%) in 19 patients without a recurrence of the disease. 70% of non-surgically treated patients vs. 50% of surgically treated were afraid of recurrence (p=0.01). Among 11 patients in drainage group, nine underwent surgery at the second episode of recurrence. CONCLUSIONS: The optimal treatment method in case of first recurrence of primary spontaneous pneumothorax is surgical treatment. When it is not possible chemical pleurodesis should be performed during pleural drainage. Most of the patients after second recurrence are treated surgically anyway. The surgical treatment significantly reduces patient's fears for future recurrence of the disease. Younger patients are most often surgically treated.

New therapy of pleural empyema by deoxyribonuclease.

Empyema is a severe complication of different diseases and traumas. Management of this complication is difficult and should comprise general and local procedures. The general procedure is mainly based on administering wide-spectrum antibiotics. Local management depends on patient general condition, but in all cases the essential procedure is to insert a drain into the pleural cavity and to evacuate the pus. Sometimes pus is very thick and its evacuation and following re-expansion of the lung is rather impossible. In these patients surgical intervention is needed. The use of intrapleural enzymes to support the drainage was first described in 1949 by Tillett and Sherry using a mixture of streptokinase and streptococcal deoxyribonuclease. Nowadays, purified streptokinase has come into widespread use, but recent studies reported no streptokinase effect on pus viscosity. On the other side, deoxyribonuclease reduces pus viscosity and may be more useful in treatment. We report two cases of intrapleural administration of Pulmozyme (alfa dornase - deoxyribonuclease (HOFFMANN-LA ROCHE AG) in dosage 2×2.5mg with a significant improvement caused by changes in pus viscosity.

Immunomagnetic detection of cancer cells in pleural effusion of generalized cancer.

Malignant pleural effusions (MPE) are a common clinical problem in patients with neoplastic disease. Pleural fluid cytology is the simplest definitive method for obtaining a diagnosis of MPE. We describe a method that may increase the cancer cell detection rate using immunomagnetic separation in MPE. In comparison to standard MPE cytodiagnostic methods, we report a more streamlined method of isolation living cells that are able to proliferate. These captured cells can then be used for additional downstream analysis e.g. chemosensitivity testing. Several case studies of MPE diagnostics using immunomagnetic separation are presented in the following report. The immunomagnetic separation of cancer cells from MPE could be used for more accurate staging of patients with routine effusions.

A clinically relevant, syngeneic model of spontaneous, highly metastatic B16 mouse melanoma.

We report a syngeneic model of spontaneous metastatic B16-F10 mouse melanoma in C57/BL6 mice with a very high metastatic frequency that mimics clinical metastatic melanoma. The B16 melanoma cells were injected between the skin and cartilage on the dorsal side of the ear. The model generated lymphatic and visceral metastases in all of the tested animals. In mice with large primary tumors, tumor weight correlated with the tumor growth time and also with the number of metastases in lymph nodes and organs. The dorsal ear space between the skin and cartilage enables both lymphatic and hematogenous metastatic spread. The model should be useful to study the mechanism of melanoma metastasis and to develop therapy for this currently untreatable disease.

New therapy of pleural empyema by deoxyribonuclease

Empyema is a severe complication of different diseases and traumas. Management of this complication is difficult and should comprise general and local procedures. The general procedure is mainly based on administering wide-spectrum antibiotics. Local management depends on patient general condition, but in all cases the essential procedure is to insert a drain into the pleural cavity and to evacuate the pus. Sometimes pus is very thick and its evacuation and following re-expansion of the lung is rather impossible. In these patients surgical intervention is needed. The use of intrapleural enzymes to support the drainage was first described in 1949 by Tillett and Sherry using a mixture of streptokinase and streptococcal deoxyribonuclease. Nowadays, purified streptokinase has come into widespread use, but recent studies reported no streptokinase effect on pus viscosity. On the other side, deoxyribonuclease reduces pus viscosity and may be more useful in treatment. We report two cases of intrapleural administration of Pulmozyme (alfa dornase - deoxyribonuclease (HOFFMANN-LA ROCHE AG) in dosage 2 × 2.5 mg with a significant improvement caused by changes in pus viscosity.