Predictive markers of response to immune checkpoint inhibitor rechallenge in metastatic non-small cell lung cancer.

Aim: The present study aims to evaluate the efficacy of rechallenge with immune checkpoint inhibitors (ICIs) compared to chemotherapy and the predictive role of clinical parameters in non-small cell lung cancer (NSCLC) patients who were rechallenged.

Methods: The study included 113 metastatic NSCLC patients who had initially responded to ICIs and platinum-based chemotherapy, either in combination in the first line or sequentially in the first and second line, but later experienced disease progression. Of those patients, 52 later received ICI rechallenge and 61 were exposed to chemotherapy.

A phase III study to access the safety and efficacy of prolgolimab 250 mg fixed dose administered every 3 weeks versus prolgolimab 1 mg/kg every 2 weeks in patients with metastatic melanoma (FLAT).

Background: Prolgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective.

Methods: We conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882).

A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma.

Background: Sasanlimab is an antibody to the programmed cell death protein 1 receptor. We report updated data of subcutaneous sasanlimab in non-small-cell lung cancer (NSCLC) and urothelial carcinoma dose expansion cohorts from a first-in-human phase Ib/II study.

Patients And Methods: Patients were ≥18 years of age with NSCLC or urothelial carcinoma, and no prior immunotherapies, who progressed on or were intolerant to systemic therapy, or for whom systemic therapy was refused or unavailable.

Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma.

Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy.

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study.

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.

Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.

Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)).

Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice.

Background: Prolgolimab is an IgG1 anti-PD-1 (programmed cell death protein 1) monoclonal antibody containing the Fc-silencing 'LALA' mutation. We assessed the efficacy and safety of two dosing regimens of prolgolimab in patients with advanced melanoma in a multicenter open-label parallel-arm phase II trial (MIRACULUM). We present the final analysis after 1 year of follow-up and additional efficacy results from 2 years of follow-up.

Variability in lung cancer response to ALK inhibitors cannot be explained by the diversity of ALK fusion variants.

Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2).

[Rigidity of psyche processes and factors predisposing to schizophrenia].

To evaluate the rigidity of psychic processes (RPP) as a factor predisposing (vulnerability) to schizophrenia and to study interactions between RPP and other susceptibility factors, psychological characteristics and magnetic resonance tomography data have been studied in 26 families with schizophrenia. Correlation, cluster and regression analyses and trait phenotypic variance decomposing into genetic and environmental components for heritability estimation were used. RPP indices in patients with schizophrenia and their relatives differed significantly from those in the control group of healthy subjects without positive family history of schizophrenia.

[The aged patient's first visit to the outpatient psychiatric clinic].

160 patients over 60 years of age appealed to gerontologic unit of out-patient psychiatric clinic for the first time. The patients were divided into two main groups: with organic mental disorders (OMD) and with functional mental disorders (FMD) (79 and 81 patients, respectively). In the group of OMD the main form of disturbances were cases with dementia (74.

[Genetic analysis of anatomical and morphologic traits of the brain, determined by magnetic resonance imaging in families of schizophrenic patients].

Genetic analysis of clinical data and data obtained by magnetic resonance imaging (MRI) on 26 families of schizophrenic patients (26 probands who were patients with schizophrenia, 47 parents, and 15 siblings) revealed an enlargement of the ventricular brain system both in probands and their affected and healthy relatives. Most MRI parameters had high coefficients of inheritance and tended to be linked with positive and negative psychopathological symptoms. Our results confirm the hypothesis of genetic predisposition to the structural changes in the brains of schizophrenic patients and suggest that such MRI characteristics as the width of the anterior horn of the left lateral ventricle in the region of the caudate nucleus, the width of the central region of the left lateral ventricle, the width of the anterior horn of the right lateral ventricle in the region of the caudate nucleus, and the width of the central region of the right lateral ventricle may serve as a marker of predisposition to schizophrenia.

[Measuring the bleomycin-induced paired damage of two DNA chains by a method of psoralen photocross-linking].

DNA of bacteriophage PM2 was allowed to react with bleomycin in the presence of Fe(II) and oxygen and the "paired" DNA lesions of two types were measured: (1) double-strand breaks, (2) lesions converted to double-strand breaks after introducing into the DNA a large number of psoralen cross-links (about 10(-2) per base pair) and alkali treatment. The mean numbers of each lesion type per DNA molecule are found to be proportional to the square of bleomycin concentration over the range of 3 X 10(-7) to 3 X 10(-6) M. These findings indicate that paired lesions are formed as a result of action of two bleomycin molecules at the same DNA site.

[Use of psoralen for detecting the conjugated damage to 2 chains in irradiated phage PM2 DNA].

Using psoralen for the photochemical cross-linking of DNA chains the authors have demonstrated the formation of conjugated lesions, of both opposite and non-opposite types, in X-irradiated superhelical DNA of PM2 phage. It is suggested that these lesions result from hitting a DNA molecule by a spur.

[Increased DNA radiosensitivity as affected by reduced derivatives of nitroimidazole and nitrofuran].

It was shown that active radiosensitizers, nitroimidazole and nitrofuran, reduced chemically and enzymatically under anaerobic conditions in the presence of DNA, cause singlestrand breaks in the latter. When this modified DNA is exposed to ionizing radiation the yield of single-strand breaks increases as compared to control (unmodified) DNA.