Novel cytokines: IL-27, IL-29, IL-31 and IL-33. Can they be useful in clinical practice at the time diagnosis of lung cancer?

There are several antiproliferative and angiogenic factors, recently have been discovered (IL-27, IL-29, IL-31 and IL-33), but they have not been tested yet in lung cancer patients. The aim of this pilot study was to assess the clinical usefulness of determination of IL-27, IL-29, IL-31 and IL-33 in advanced stages of lung cancer. Patients and Methods: The study included 45 patients (38 males; mean age 62 years; 45 with advanced NSCLC). Serum and BALF cytokine concentrations were evaluated by ELISA method before chemotherapy. The comparative groups consisted of patients with sarcoidosis (BBS, n = 15), hypersensivity pneumonitis (HP, n = 8) and healthy subjects (n = 15). Results: The serum IL-29 levels were higher in NSCLC patients than in the sarcoidosis group. However, serum IL-27, IL-31 and IL-33 did not differ markedly between: NSCLC, BBS, HP and the control group. Concentrations of IL-29 and IL-31 in BALF did not differ significantly between investigated groups. In all groups levels of IL-27 and IL-29 are significantly higher in serum than in BALF. Concentrations of IL-31 in BBS, HP and control groups tended to higher in BALF than in serum. These differences were significantly in NSCLC patients. Patients in stage IIIB of NSCLC had higher serum levels of IL-29 than these in stage IV. Lung cancer patients with partial remission (PR) after chemotherapy had significantly higher concentration of IL-27 in BALF than patients with SD. However, patients with SD had higher levels of IL-29 in BALF than patients with PD. A negative correlation was found between serum IL-31 levels before therapy and time to progression of NSCLC. Conclusion: Determination of IL-27, IL-29 and IL-31 in serum and BALF can be useful in clinical practice, but their practical significance needs further studies

Serum levels of sFas and sFasL during chemotherapy of lung cancer

The aim of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during chemotherapy of lung cancer. Methods: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC). The control group consisted of 15 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. sFas and sFasL levels were assessed by Elisa method. Results: The serum sFas and sFasL levels observed at the end of the chemotherapy were higher in all patients with lung cancer compared to healthy volunteers. The levels of sFas and sFasL were higher after chemotherapy than before therapy. The levels of sFasL were significantly higher in SCLC patients than in NSCLC ones. There were no significant differences in serum sFasL levels in relation to clinical stage of lung cancer. After chemotherapy the levels of sFas were higher in patients with metastases. There were no significant differences in serum sFasL levels in relation to response to therapy. At the end of the therapy the serum levels of sFas were higher in Partial Response group than in Progressed patients. Before chemotherapy the levels of sFas were higher in Progressive Disease group than in No Change one. The levels of sFas observed after chemotherapy were higher in Partial Response group than in No Change one. Conclusion: Determination of serum sFas and sFasL levels can be useful in clinical practice, but their practical significance needs further studies.Цель работы —оценить клиническую целесообразность определения уровня растворимого Fas (sFas) и растворимого лиганда Fas (sFasL) в сыворотке кровибольных раком легкого при химиотерапии. Методы: обследовали 80 пациентов (69 мужчин и 11 женщин; средний возраст — 64 года; из них у 48 диагностирован немелкоклеточный рак легкого (НМКРЛ), у 32 — мелко­клеточный рак легкого (МКРЛ)). Контрольная группа состояла из 15 здоровых доноров. Образцы периферической крови брали до и после 4 курсов химиотерапии. Содержание sFas и sFasL ана лизировали иммунофер ментным методом. Результаты: уровни sFas и sFasLв сыворотке крови всех больных раком легк ого по окончании хими отерапии выше, чем таковые в контрольной группе и чем таковые до терапии. Уровень sFasL был значительно выше у больных МКРЛ, чем таковой у пациентов с НМКРЛ. Значительных различий в уровне sFasLв сыворотке крови в за висимости от клинической стадии заболевания не выявлено. По окончании химиотерапии уровень sFas выше у пациен тов с метастазами, а также в группе с частичным ответом на терапию, чем у больных с прогрессирующим заболеванием. До начала терапии уровень sFas был выше у больных с прогр ессирующим забо лева нием, чем у па циентов со стабильным состоянием , а по окончании терапии – у больных с частичным ответом по сравнению с группой больных со стабильным состоянием. Выводы: определение уровня sFas и sFasLв сыворотке крови может быть пр именено в клинической практике, но зна чимость та ких показателей необходимо определить в дальнейших исследованиях

Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma

<p>Abstract</p> <p>Background</p> <p>N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of <it>NMDAR2B </it>in non-small cell lung cancer (NSCLC) are unknown.</p> <p>Methods</p> <p>The relationship between gene methylation and expression of <it>NMDAR2B </it>was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of <it>NMDAR2B </it>methylation.</p> <p>Results</p> <p><it>NMDAR2B </it>was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of <it>NMDAR2B</it>, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases.</p> <p>Conclusions</p> <p>Aberrant methylation of the <it>NMDAR2B </it>gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which <it>NMDAR2B </it>was methylated. It may have different roles in different histological types.</p

Impact of p16 status on pro- and anti-angiogenesis factors in head and neck cancers.

BACKGROUND: Head and neck cancers (HNC) are aggressive tumours. Overexpression of p16 in HNC correlates with human papilloma virus (HPV)-associated HNC that carry a better prognosis than HPV-negative tumours. Angiogenesis is an important factor in tumour progression. Our aim was to dissect the impact of p16 expression on angiogenesis factors in HNC. METHODS: Eighteen newly diagnosed HNC patients and controls were analysed. Eleven pro- and anti-angiogenesis factors were quantified using multiplex ELISA in HNC patients and controls. Angiogenesis factors were analysed in tumour tissue using immunohistochemistry. RESULTS: Circulating levels of endostatin (anti-angiogenesis factor) were higher in the HNC group compared with healthy donors. Interestingly, the pro-angiogenesis factors angiopoietin-1 and vascular endothelial growth factor (VEGF) were significantly higher in patients with p16-negative compared with p16-positive HNC. Moreover, the major source of VEGF in p16-positive HNC tissue was tumour stromal cells. In contrast, both tumour cells and stromal cells expressed VEGF in p16-negative tissue. CONCLUSIONS: We show that p16-negative tumours associate with increased circulating levels of pro-angiogenic VEGF and angiopoietin-1. Tissue expression of VEGF differs between p16-positive and p16-negative tumours. These findings may explain differences in the biological behaviour of p16-positive and p16-negative HNC. Better understanding of mechanisms by which the p16 status influences tumour angiogenesis may guide the development of targeted therapies