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 cathepsin K and cystatin C concentration in patients with advanced non-small-cell lung cancer during chemotherapy.

A pathogenic implication of cathepsin K (Cath K) and its inhibitor - cystatin C (Cyst C) occur to be of growing importance in the mechanisms of tumor invasiveness in lung cancer. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum Cath K and Cyst C (ELISA) in patients with advanced stage non-small cell lung cancer (NSCLC). The study entered 40 patients (32 men) and 15 healthy volunteers (control group). Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum Cyst C levels were significantly higher in patients with advanced NSCLC than in controls (p=0.003). The levels of Cath K in serum of NSCLC are comparable to those in controls. No correlation was found between Cath K and Cyst C concentrations and the histological type and staging of lung cancer. Patients with T4-stage had a lower level of Cyst C, than those with T2 (p=0.033). No correlation was found between the concentrations of Cath K, Cyst C and the effect of chemotherapy. However, Cyst C level positively correlated with serum creatinine concentration (R=0.535; p=0.005) in patients who responded to chemotherapy and with patient's age (R=0.456; p=0.018) in whole group. When the cut-off values of serum Cath K and Cyst C (23.35 pmol/l, 1.29 mg/l, respectively) were used, the prognoses of high and low groups were not different. Concluding, patients with lung cancer have a higher serum concentration of Cyst C compared to healthy people. In our opinion, determination of Cath K and Cyst C concentrations has no clinical significance in the prognosis of the survival time in lung cancer

Dapagliflozin therapy for patients with CKD according to current guidelines and clinical trials

The publication of the DAPA-CKD study in 2020 has revolutionised the strategy of nephroprotective therapy in chronic kidney disease (CKD) worldwide. From 01.07.2022 we have a reimbursement of dapagliflozin registered for nephrological indications in Poland. However, the lack of specific guidelines for the use of SGLT2 inhibitors in CKD patients creates a barrier to their widespread use. Hence, the recommendations of other European countries published so far have been reviewed and an attempt was made to translate them into Polish background. Certain concerns about the new treatment strategy were also highlighted and discussed. In the near future, we should expect the publication of the official position of the Working Group of the Polish Nephrology Society on this item

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

OPG/RANK/RANKL signaling system and its significance in nephrology.

Recent years brought the discovery of new members of TNF receptor superfamily - osteoprotegerin/receptor activator of nuclear factor-kappaB and its ligand (OPG/RANK/RANKL) system as regulator of bone remodeling. Further studies showed its involvement in control of vascular and immune system. Animal studies' results confirm the OPG/RANK/RANKL role in pathogenesis of vascular calcifications and osteoporosis. Human studies, especially in patients with chronic kidney disease (CKD), have brought many conflicting data. Understanding of exact contribution of each molecule creating this axis may be crucial for diagnosis and treatment of CKD complications involving renal osteodystrophy and vascular calcification. In this review we try to summarize recent knowledge and OPG/RANK/RANKL role in patient with chronic kidney diseases

Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy.

Recently, several reports have suggested that HMGB1 (the high-mobility group box-1) plays a key role in tumor angiogenesis through multiple mechanisms, including up-regulation of proangiogenic factors. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum (ELISA) angiogenic factors: HMGB1, survivin and VEGF (Vascular Endothelial Growth Factor) in patients with advanced stage non-small cell lung cancer (NSCLC). The study entered 40 patients (31 man) and 15 healthy volunteers (control group). Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum HMGB1 and VEGF levels were significantly higher in patients with advanced NSCLC than in controls (p=0.024, p=0.028, respectively). The levels of survivin in NSCLC patients were comparable to controls. No correlation was found between HMGB1, survivin and VEGF concentrations and the histological type and staging of lung cancer. Similarly, no correlation was revealed between the concentrations of HMGB1, survivin and VEGF and the effect of chemotherapy. However, in patients with NSCLC, HMGB1 positevely correlated with survivin (R=0.814, p=0.007) before chemotherapy, and negatively with VEGF (R=-0.841, p=0.035) after chemotherapy. When the cut-off values of serum HMGB1, survivin and VEGF (2.38 ng/ml, 81.92 pg/ml, 443.26 pg/ml, respectively) were used, the prognoses of high and low groups were not different. Concluding, patients with NSCLC have a higher serum concentration of HMGB1 and VEGF, while survivin levels are comparable to healthy individuals. In our opinion, determination of HMGB1, survivin and VEGF concentrations has no clinical significance in the prognosis of the survival time in lung cancer

The influence of unfractionated and low-molecular weight heparins on the properties of human umbilical vein endothelial cells (HUVEC).

Heparins, as anticoagulants widely used in the prophylaxis and treatment of many conditions connected with hypercoagulability, have a potent effect on the vascular endothelium. Unfractionated Heparin (UFH) is characterized by relatively low biological accessibility, short activity time, binding of numerous proteins, as well as unfavorable influence on endothelium and blood platelets. Low-Molecular Weight Heparins (LMWHs), formed by chemical and enzymatic UFH depolymerizations, show a significantly more favorable impact on endothelium, which was confirmed on the HUVEC cultures study models. The studies on the heparins' modulation of angiogenesis process proved the superiority of LMWHs over UFH. It was connected with a better deactivation of growth factors' receptors (e.g. for VEGF165, FGF-2). Comparing the effects of LMWHs and UFH on haemostatic and antiangiogenic properties of HUVEC, significant differences were found as well. A new effect, engaging these compounds in the pathomechanism of an excessive osteoclastogenesis via osteoprotegerin /RANKL/RANK pathway has been discovered recently

Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensivity pneumonitis and idiopathic pulmonary fibrosis.

The process of interstitial inflammation, often chronic, goes fluently from alveolitis through granuloma formation to irreversible fibrosis and lung remodeling. Eventually, the loss of functional alveolar units leads to chronic respiratory failure. The pneumoproteins (e.g. SP-D, CC-16) are considered to be markers of interstitial inflammation. We measured BAL concentration of SP-D, CC-16 and IL-10 in patients with sarcoidosis (27), IPF (7) and HP (9). The level of each marker was determined by ELISA specific kit. We found the highest SP-D and CC-16 BAL concentration in patients with the III stage of sarcoidosis (96,67 ng/ml and 31,78 ng/ml, respectively). The lowest SP-D concentration was observed in patients with IPF (76,49 ng/ml), and the lowest CC-16 concentration in patients with HP (21,39 ng/ml). The differences were not statistically significant. In the group of the III stage of sarcoidosis higher SP-D levels were related to higher BAL cytosis and higher percentage of BAL neutrophils, just the opposite as in the IPF and HP group. In the III stage of sarcoidosis and HP, the lower SP-D levels, the lower FEV1 and VC values. The results show, that in acute interstitial inflammation with larger parenchyma engagement (III stage of sarcoidosis) the levels of SP-D were higher then in chronic interstitial inflammation (IPF)

The usefulness of the Body Composition Monitor device in the evaluation of the volume status in the peritoneal dialysed patients — case report

Euwolemia jest bardzo ważnym parametrem adekwatności dializy otrzewnowej. W praktyce klinicznej ocena stanu nawodnienia może być trudna. Przydatność urządzenia BCM w ocenie składu ciała oraz stanu nawodnienia u chorych dializowanych otrzewnowo została udowodniona. W niniejszym artykule przedstawiono dwa przypadki korzyści wynikających z praktycznego zastosowania tego urządzenia.Euvolemia is very important adequacy parameter of peritoneal dialysis. In clinical practice volume status assessment may be difficult. Usefulness of Body Composition Monitor device was proven in estimation volume status of peritoneal dialysed patients. In this article two cases of benefits connected with using of this device were presented

Immunohistochemical markers of cancerogenesis in the lung.

Lung cancer is the leading cause of cancer deaths for people of both sexes worldwide. Early diagnosis of precancer lesions may be of crucial significance to lowering lung cancer mortality. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia and carcinoma in situ, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. Apart from WHO classification, two other lesions such as bronchiolization and bronchiolar columnar cell dysplasia (BCCD) can be observed and thought to be preneoplastic lesions leading to adenocarcinoma. In this review we summarize the data of morphological and cell cycle related proteins changes in both central and peripheral compartments of lung. Many molecular changes, which accompany the multistep process of the development of invasive types of cancer, may be observed thanks to the application of immunohistochemical markers. A deeper knowledge of molecular and genetic changes accompanying pre-cancer states may show new directions of early diagnostics of cancer development