Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

Challenges Faced by Clinicians in the Personalized Treatment Planning: A Literature Review and the First Results of the Russian National Cancer Program.

Advances in cancer molecular profiling have enabled the development of more effective approaches to the diagnosis and personalized treatment of tumors. However, treatment planning has become more labor intensive, requiring hours or even days of clinician effort to optimize an individual patient case in a trial-and-error manner. Lessons learned from the world cancer programs provide insights into ways to develop approaches for the treatment strategy definition which can be introduced into clinical practice. This article highlights the variety of breakthroughs in patients' cancer treatment and some challenges that this field faces now in Russia. In this report, we consider the key characteristics for planning an optimal clinical treatment regimen and which should be included in the algorithm of clinical decision support systems. We discuss the perspectives of implementing artificial intelligence-based systems in cancer treatment planning in Russia.

Adiponectin: a pleiotropic hormone with multifaceted roles.

Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

[Development of aseptic osteonecrosis during the treatment of acute lymphoblastic leukemia: review of the literature and author's own data].

We report a case of aceptic osteonecrosis (AON) of the left hymerus epiphysis in programmed treatment of a male patient with lymphoblastic lymphoma to illustrate clinical, laboratory, epidemiological, pathogenetic, diagnostic and therapeutic aspects of AON in programmed therapy of acute lymphoblastic leukemia (ALL). We believe that AON is a rather frequent but often missed for early diagnosis complication of ALL treatment. Even a weak pain in bones and joints under mechanical load in patients on long-term treatment with glucocorticosteroids is an alarming symptom which may indicate a risk of an osteodestructive process and relevant diagnostic and therapeutic measures may be needed.

[Velcade in multiple myeloma].

AIM: To study efficacy of velcade therapy in patients with progressive or refractory multiple myeloma (MM). MATERIAL AND METHODS: From April 2005 to November 2006 velcade was used in therapy of 18 patients (11 females and 7 males) with progressive or refractory to prior standard therapy MM course. The patients' age median was 55 years (36 to 76 years). Velcade was injected intravenously on the course days 1, 4, 8 and 11 with interval 10 days between the courses. A total of 77 courses were made (median 4.5). RESULTS: Overall efficacy was assessed according to EBMT criteria in 16 (68%) patients. Partial remission (PR) was achieved in 9 patients, complete remission (CR)--in 1, minimal response (MR)--in 1 patient. Five patients failed the treatment. In 5 of 11 patients with confirmed efficacy of velcade the drug was used in induction of remission before high-dose chemotherapy (HDC) and autotransplantation of hemopoietic stem cells (HSC), in 3--as monotherapy, in 1--in combination with high-dose dexamethasone, in--with high dose dexamethasone and doxorubicin. Four patients achieved PR, one--MR. HSC were obtained before velcade therapy in one patient, in 4--after its conduction. After HDC there were one CR and 4 PR. Recovery of hemopoiesis after HDC took the same time as after standard induction therapy. In 6 of 11 patients HDC was not performed. Velcade therapy is continued in 2 patients, in 1 case with CR the treatment was stopped. In 3 cases PR for 2 to 6 months was followed by the disease progression. CONCLUSION: Velcade as a new effective antitumor drug can be used for treatment of progressive and refractory forms of MM.

[LMP1 gene variants of Epstein-Barr virus in patients with some lymphoproliferative malignancies].

The samples of tumor biopsy, blood, and saliva from 10 patients with Hodgkin's disease, 10 patients with non-Hodgkin's lymphoma, and the blood samples of 20 donors were tested by polymerase chain reaction (PCR) for standard (wild) B95-8 and Cao-like (deleted) variants of the LMP1 gene. The paraffin sections of most PCR-tested tumors were also investigated by immunohistochemistry using the monoclonal antibodies S12 or 7D7 to detect the expression of the standard or Cao-like variants of LMP1 protein, respectively. It is suggested that Eptein-Barr virus (EBV) that contains the above deletion is not crucial for the development of the study lymphoproliferative malignancies. The fact that in some cases there is the Cao-like variant of LMP1 in the tumor biopsy specimen and its standard variant LMP1-B95-8 in the biological fluids of the same patient is very likely to suggest that the patient is infected with both types of the virus or there is genetic mutation(s) of EBV during viral carcinogenesis preceding or accompanying the development of a tumor.