Номінація частин руки в говірці села Невгоди Овруцького району Житомирської області

У статті розглянуто лексеми на позначення частин руки в сучасній середньополіській говірці, зокрема проаналізовано їхню семантику та мотивацію.В статье рассматриваются лексемы, обозначающие части руки, в современном среднеполесском говоре, а именно проанализирована их семантика и мотивация.The article deals with lexemes on designations of parts of the manuscript in the middle-polissya dialect. Their semantics and motivation are also analyzed

A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer

Background This was a first-in-human Phase 1/2 open-label dose-escalation study of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737. Methods Patients with advanced solid tumours enrolled in dose-escalation cohorts and received SRA737 monotherapy orally on a continuous daily (QD) dosing schedule in 28-day cycles. Expansion cohorts included up to 20 patients with prospectively selected, pre-specified response predictive biomarkers. Results In total, 107 patients were treated at dose levels from 20–1300 mg. The maximum tolerated dose (MTD) of SRA737 was 1000 mg QD, the recommended Phase 2 dose (RP2D) was 800 mg QD. Common toxicities of diarrhoea, nausea and vomiting were generally mild to moderate. Dose-limiting toxicity at daily doses of 1000 and 1300 mg QD SRA737 included gastrointestinal events, neutropenia and thrombocytopenia. Pharmacokinetic analysis at the 800 mg QD dose showed a mean Cmin of 312 ng/mL (546 nM), exceeding levels required to cause growth delay in xenograft models. No partial or complete responses were seen. Conclusions SRA737 was well tolerated at doses that achieved preclinically relevant drug concentrations but single agent activity did not warrant further development as monotherapy. Given its mechanism of action resulting in abrogating DNA damage repair, further clinical development of SRA737 should be as combination therapy. Clinical trial registration Clinicaltrials.gov NCT02797964

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4–4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3–1.6) for placebo (HR = 0.64, 95% CI: 0.38–1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6–4.2) months for brivanib and 2.0 months (95% CI: 1.2–2.7) for placebo (HR: 0.56, 95% CI: 0.26–1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6–4.2) and was 2.0 months (95% CI: 1.2–2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25–1.17; p = 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib

Intra-Peritoneal Administration of Genetic Therapies: promises and pitfalls

Rapid advances in our understanding of the molecular basis of cancer development and progression over the past 3 decades have led to the design of new potential cancer therapies based on the expression of introduced genes into a tumor or its host. In an attempt to overcome the limitations of direct intratumoral administration of genetic therapies in patients with advanced malignant disease, loco-regional routes of delivery have been explored including the intraperitoneal route. This review highlights the potential of replication-competent oncolytic viruses, virus-mediated gene replacement, and gene-directed enzyme-prodrug strategies, as novel cancer therapies. The potential of exploiting the selectivity of the telomerase gene within cancer cells to develop gene therapy strategies is discussed and the promises and pitfalls in translating these novel therapeutics from the laboratory to the clinic are reviewed

Gemcitabine elaidate cytotoxic agent oncolytic

Cemcitabine is an established chemotherapeutic agent for the treatment of a variety of malignancies, including pancreatic, bladder, breast and non-small cell lung cancers. Cemcitabine requires specialized nucleoside transporters, which facilitate its entry into cells, and there is a growing body of evidence suggesting that these nucleoside transporters play a key role in gemcitabine sensitivity. Gemcitabine elaidate (CP- 4126, gemcitabine-5'-elaidic ester), is a novel cytotoxic agent that permeates the cell membrane independent of nucleoside transporters. A phase I trial of CP-4126 in patients with solid malignancies has shown promising antitumor activity. In this review, we discuss the origin, mechanism of action, preclinical and clinical evidence of antitumor activity of this novel drug

Coexistent malignant melanoma and renal cell carcinoma

Patients with malignant melanoma are at an increased risk of developing subsequent primary melanomas and also nonmelanoma cutaneous cancers. Several studies have reported an association between malignant melanoma and breast cancer, bladder cancer, colorectal cancer, neuroectodermal tumours, non-Hodgkin's lymphoma, leukaemia and renal cell carcinoma. We report a case series of patients with a diagnosis of malignant melanoma who also developed a renal mass. In two of these cases, the renal mass became apparent on diagnostic imaging as part of the staging investigations at the time of initial diagnosis of the malignant melanoma. In both of these cases, biopsy of the renal mass confirmed the presence of a separate primary renal cell carcinoma which had presented concurrently with the malignant melanoma. A third case presented with bone metastases ten years after excision of a thin melanoma. Further imaging revealed pulmonary metastases and a renal mass, biopsy of which confirmed renal cell carcinoma. In contrast, a fourth patient underwent a right nephrectomy for a renal mass having presented with abdominal discomfort. The histology of this lesion was in keeping with metastatic melanoma, and the patient's past history included a diagnosis of ocular melanoma eight years prior to the development of metastatic disease in the right kidney. Survival rates for patients with many types of malignant disease are improving, and there have been significant advances in clinical imaging techniques. Consequently the development and detection of a second primary cancer, either presenting concurrently or on subsequent follow-up, is likely to be increasingly observed. The series of patients reported here highlights the importance of a diagnostic biopsy in patients with malignant melanoma who develop a renal mass in order to establish a diagnosis and to plan optimal treatment

Vitamin D analogues as anti-cancer therapies

No abstract available

Unknown primary

No abstract available