Застосування українського досвіду визначення кроку встановлення рамного кріплення підготовчих виробок для польських шахт

На основі детального аналізу наявного досвіду встановлення рамного кріплення підготовчих виробок на шахтах України та застосування перевірених методик визначення навантажень на окремі його елементи запропоновано концепцію збільшення кроку інсталяції рамноаркового кріплення на шахтах Польщі. Економічну оцінку запропонованого технологічного удосконалення проведено, ґрунтуючись на відносних одиницях для більш точного відображення мінливого ринку гірничої промисловості. Як удосконалення запропоновано стандартний для український шахт крок встановлення кріплення

Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition

The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)—an essential element of the metastatic process—is frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the “capture” of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)—cmHsp70.1—can be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression

Targeted natural killer cell–based adoptive immunotherapy for the treatment of patients with NSCLC after radiochemotherapy: a randomized phase II clinical trial

Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in apatient with NSCLC stage IIIb inducing long-term tumor control: Acase study.

BackgroundMembrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as atumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) and Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, and programmed death(PD)-1 inhibition were combined to improve the efficacy of tumor-specific immune cells in anon-small cell lung carcinoma (NSCLC) patient.PatientFollowing simultaneous RCT (64.8Gy), apatient with inoperable NSCLC (cT4, cN3, cM0, stage IIIb) was treated with 4cycles of autologous ex vivo TKD/IL-2-activated NK cells and the PD-1 antibody nivolumab as asecond-line therapy. Blood samples were taken for immunophenotyping during the course of therapy.ResultsAdoptive transfer of ex vivo TKD/IL-2-activated NK cells after RCT combined with PD-1 blockade is well tolerated and results in superior overall survival (OS). No viable tumor cells but amassive immune cell infiltration in fibrotic tissue was detected after therapy. Neither tumor progression nor distant metastases were detectable by CT scanning 33months after diagnosis. Therapy response was associated with significantly increased CD3(-)/NKG2D(+)/CD94(+) NK cell counts, elevated CD8(+) to CD4(+) Tcell and CD3(-)/CD56(bright) to CD3(-)/CD56(dim) NK cell ratios, and significantly reduced regulatory Tcells (Tregs) in the peripheral blood.ConclusionAcombined therapy consisting of RCT, mHsp70-targeting NK cells, and PD-1 antibody inhibition is well tolerated, induces anti-tumor immunity, and results in long-term tumor control in one patient with advanced NSCLC. Further, randomized studies are necessary to confirm the efficacy of this combination therapy