Experimental oncology最新文献

To the Editor, Head and neck squamous cell carcinoma (HN- SCC) accounts for about 600,000 new cases globally every year and stands the sixth most common cancer, arising from the squamous epithelium. It is localized in the head and neck area involving oral cavity, pharynx, and larynx. Despite the rigorous therapy, the 5-year overall survival remains poor in HNSCC and has not changed appreciably in the last 30 years. The majority of patients develop resistance to chemotherapeutic agents, and cancer progression occurs. Cetuximab, which targets the epidermal growth factor receptor, and pembrolizumab, an anti-programmed-death ligand 1 antibody, are among few FDA-approved medications. Current therapies are poor and cause severe long-term toxicity, which has a long-term impact on the quality of life [1].......

The clinical case of a patient with multicentric breast cancer who underwent organ-sparing surgery after neoadjuvant chemo-radiation therapy is presented. An ipsilateral cancer recurrence was diagnosed 8 years after the first operation. The repeated organ-sparing surgery (lumpectomy) was done with a good cosmetic result and without disease progression during 1-year follow-up. The literature review shows that neoadjuvant systemic therapy accounting for molecular subtypes of cancer has radically changed breast cancer surgeries. The evolution of surgical approaches in stage I-II breast cancer patients consists in the de-escalation of surgery from mastectomy to organsparing or oncoplastic surgery, minimally directed surgery, and repeated breast-conserving surgery. De-escalation of surgical interventions in the area of the regional lymphatic collector consists in the transition from total axillary lymphatic dissection to sentinel lymph node biopsy or targeted removal of metastatic lymph nodes. The repeated breast-conserving surgery can be safely performed for ipsilateral recurrence in patients with all molecular subtypes of breast cancer.

Aim: To evaluate the effect of B. subtilis IMV B-7724 lectin on the functional activity of macrophages (Mph), natural killer (NK) cells and cytotoxic lymphocytes (CTL) of mice bearing Lewis lung carcinoma (LLC).

Materials and methods: The studies were performed on C57Bl/6J mice; LLC was used as an experimental transplantable tumor. The lectin from B. subtilis IMV B-7724 was administered to LLC-bearing mice subcutaneously at a dose of 1 mg/kg of body weight for 10 days. The immunological testing was performed on days 14, 21, and 28 after tumor grafting. The cytotoxic activity of Mph, NK, and CTL was estimated in MTT-assay; the content of the stable metabolites of nitric oxide (NO) was measured by a standard Griess reaction; the arginase activity (Arg) was determined based on the measurement of urea.

Results: The administration of the B. subtilis IMV B-7724 lectin to LLC-bearing mice exerted its antitumor and antimetastatic effects partially via a significant (p < 0.05) increase of Mph and NK activities after the completion of the treatment. In the group of animals injected with lectin, the NO/Arg ratio increased significantly, indicating the prevalence of Mph with proinflammatory and antitumor properties. The cytotoxic activity of Mph exceeded the indices of untreated mice and intact control by 1.8 times and 5.3 times respectively; of NK - by 2.8 and 1.3 times respectively. The effect of treatment on the CTL activity was less pronounced.

Conclusion: Antitumor and antimetastatic activity of the lectin from B. subtilis IMV B-7724 ensured the preservation of the cytotoxic activity of the main effectors of antitumor immunity (Mph, NK, and CTL) throughout LLC growth.

Background: Glioblastoma (GBM) is the most frequent primary malignant CNS tumor. Deficient mismatch repair (dMMR) is associated with better prognosis and is a biomarker for immunotherapy. Evaluation of MMR by immunohistochemistry (IHC) is accessible, cost effective, sensitive, and specific.

Aim: Our objective was to investigate MMR proteins in adult GBM patients.

Materials and methods: We retrospectively analyzed 68 GBM samples to evaluate the proficiency of MMR genes expression assessed by IHC. Clinicopathologic and molecular features were compared in proficient (pMMR) or dMMR.

Results: 10 (14.7%) samples showed dMMR, and the most frequent was MSH6 (100%) followed by MSH2, PMS2, and MLH1. We observed heterogeneous expression of dMMR in 5 GBMs. The median overall survival did not differ between pMMR (19.8 months; 0.2-30) and dMMR (16.9 months; 6.4-27.5) (p = 0.31). We observed a significantly higher overall survival associated with gross total resection compared to subtotal resection or biopsy (30.7 vs. 13.6 months, p = 0.02) and MGMT methylated status (29.6 vs. 19.8 months, p = 0.049). At the analysis time, 10 patients were still alive, all in the pMMR group.

Conclusions: Our data demonstrated dMMR phenotype assessed by IHC in an expressive portion of GBM patients, however without significant impact on overall survival.

This article briefly summarizes our long-term experience of research in the field of experimental and clinical radiation oncology unified by the key word "radiosensitivity". Consistently presented and interpreted here are the main results on biodosimetry of irradiation depending on doses and quality of ionizing radiation and determination of individual radiosensitivity of cancer patients. We justified the use of radiomitigators to reduce the frequency and severity of post-radiation complications in cancer patients, and for radiation protection of the general population. The radioprotective effect of the antioxidant inosine in the somatic cells of cancer patients in the range of low radiation doses was demonstrated. We established that in persons who are hypersensitive to irradiation, the reparative potential is reduced by about 60% compared to ones with normal indices of individual radiosensitivity. Cytogenetic predictors of radiosensitivity of healthy cells adjacent to the irradiated tumor have been determined. Unfortunately, they have not yet become a point of application for individual planning of irradiation courses and assessment of severity of post-radiation complications. The intensive development of selective radioprotectors that would selectively protect healthy tissues in the course of radiation therapy, reducing their radiosensitivity by activating reparation processes, is considered a priority direction of modern radiation oncology.

Background: Disseminated peritoneal leiomyomatosis (DPL) is an extremely rare benign disease characterized by widespread lesions of the abdominal cavity, pelvis, and retroperitoneal space with tumor nodules of varying size and number, which are benign neoplasms consisting of smooth muscle fibers in their histological structure.

Aim: To analyze clinical cases of DPL with a concise review of the current state of the DPL diagnosis and treatment.

Materials and methods: We analyzed 5 clinical cases of DPL of female patients aged 39-50 years (mean age 46.2 years) who underwent surgical treatment at the National Cancer Institute from 2010 to 2021. In all 5 patients, the diagnosis of DPL (8898/1) was verified according to pathological (using routine hematoxylin/eosin staining) and immunohistochemical (IHC) studies.

Results: All patients underwent surgical treatment with a laparotomy approach, the extent and radicality of which depended on the location and number of tumor lesions. At the time of follow-up, all 5 patients were alive and did not receive any special oncological treatment.

Conclusions: DPL is characterized by a variety of clinical manifestations from polyserositis to acute abdomen, depending on the location and size of the main tumor focus. IHC analysis is the criterion for the final diagnosis, and radical removal of all tumor foci provides the best therapeutic prognosis. The treatment should be carried out in highly specialized cancer centers where surgeons have gained sufficient experience in performing cytoreductive surgery.

The right trisectionectomy is the main treatment modality for locally advanced gallbladder cancer with invasion of the intraparenchymal portal vein branches because it allows the achievement of negative resection margins (R0). However, only 10%-25% of such patients are eligible for surgery. The cryosurgical method has been successfully used in the complex treatment of hepatopancreatobiliary malignant neoplasms for many years. The possibility of its application close to major blood vessels is one of its advantages. In the presented case, the cryodestruction of the residual tumor with invasion into the anterior wall of the left branch of the portal vein was used as a debulking option during liver resection (R2) due to locally advanced gallbladder cancer. The cryodestruction was performed with application method with a double cryocycle and spontaneous thawing using a Cryo-Pulse device and liquid nitrogen as a cryoagent. No postoperative complications related to cryodestruction were noted. The cryogenic technologies application in the debulking surgery of gallbladder cancer can be a safe treatment modality for residual tumors with invasion into the intraparenchymal branches of the portal vein.

On June 14-16 2023, the 45th meeting of the General Assembly of Organization of European Cancer Institutes (OECI) dedicated to the 120th anniversary of the award of the first Nobel Prize in Physics for the discovery of radioactivity to Marie Skłodowska-Curie was held in Paris hosted by the Institut Curie. More than 130 leading specialized institutions and organizations that focus their efforts on finding ways and optimizing coordination to improve the quality of cancer care in Europe attended the OECI Oncology Days and the General Assembly. The first plenary session, chaired by S. Oberst and J.-B. Burrion, was devoted to the issues of quality in oncology and the role of research and education in optimizing healthcare services. It was noted that today, in the field of providing medical services to cancer patients in European countries, there are significant differences in access to digital, research and innovation technologies. The efforts of the team in the field of accreditation and certification of cancer centers within the framework of the European Cancer Plan help to improve and build the capacity of the EU member states to improve the quality of healthcare services. The OECI is working to support, improve and integrate cancer patient care, research and education in cancer care as well as survivorship to minimize inequalities in access to quality health care. A separate session chaired by E. Jolly was devoted to the role of patient organizations in improving the quality of cancer care, research and education. The reports presented the best experiences of cooperation between cancer centers and patient organizations in Central and Eastern Europe, as well as models of increasing interaction between clinical research centers and patient organizations in the European Union and Japan. The OECI is making considerable efforts to create an optimal model of the pathway that a patient should follow from the moment of diagnosis to palliative care and long-term survival. Optimization of European standards for the provision of high-quality specialized medical care and the development of quality indicators and patient-reported outcomes will improve the ability of researchers and healthcare providers to combine their efforts. On the one hand, the patient pathway is a tool for improving the quality of medical services and patient care, and on the other hand, it guarantees cost control and takes into account the patient's experience to make the best decision by a multidisciplinary team. At the session chaired by M. Nilsert, the best practices of oncology care provided by OECI-certified centres in Toulouse, Helsinki, Stockholm (Karolinska) and Dublin were presented. It is convincingly proven that the certification procedure helps to optimize the quality of medical services, communication with patients, research and improve the quality of education. Considerable attention at the special session chaired by G. Apolone and G. Brunelli was devoted to the issue

Background: Effective prediction of the course of prostate cancer (PCa) and the stratification of treatment tactics largely depend on the use of prognostic markers that reflect the molecular and biological features of tumors. In view of the important role of matricellular proteins in the modulation of the growing tumor and metastasis of the hormone-dependent neoplasms, the aim of the work was to study the expression of osteopontin (OPN) at the protein and mRNA levels in the PCa tissue in order to assess the significance of this protein for predicting the aggressiveness of PCa.

Materials and methods: The work is based on the analysis of the results of the examination and treatment of 83 patients with PCa of stages II-IV. The study of OPN expression at the level of mRNA and protein in the PCa tissue was carried out using methods of the real time polymerase chain reaction and immunohistochemistry, respectively.

Results: The OPN expression in the PCa tissue was 1.6 times (p < 0.05) higher in patients with regional lymph node metastases compared to patients without metastases. In patients with a Gleason score of < 7, the OPN expression in the tumor tissue was 1.4 times lower (p < 0.05) than in patients with poorly differentiated PCa. In patients with a high risk of tumor progression, the OPN expression level was 1.4 and 2.1 times higher (p < 0.05) compared to patients with a moderate and low risk of PCa progression. The patients with a high OPN expression level in the PCa tissue had significantly decreased 2-year recurrence-free survival rate (by 25%).

Conclusions: The obtained results indicate the expediency of using OPN expression indicators in the tumor tissue to predict the PCa aggressiveness and assess the risk of its recurrence.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults. The improvement of the efficacy of GBM treatment is an urgent problem encouraging the development of novel therapeutic strategies, in particular, immunotherapeutic modalities. With more understanding of the intimate interrelationships between the immune system and the mechanisms involved in cancer origin and progression, the skepticism related to the relevance of the immunotherapeutic approaches in the treatment of brain tumors is gradually decreasing. The review discloses the modern concepts on the association between CNS and the immune system. For a long time, CNS was considered as the immunoprivileged site that prevents the effects of immunotherapy in the treatment of brain tumors. Nowadays, these views are reconsidered, which opens the way to the use of immunotherapeutic approaches in GBM treatment. The results of the recent clinical trials on immunotherapy as a supplement to the conventional GBM treatment are considered. Vaccines based on the dendritic cell (DC) technology are regarded as the most promising for this purpose. The preliminary results of the Ukrainian clinical study are also presented and discussed. The results of the international clinical trials as well as our own experience give evidence of the relevance for using DC vaccines in the complex treatment of GBM, which is supported by the increased survival of patients and the safety of vaccine application. It is of high importance that GBM patients with the most unfavorable prognosis can benefit from DC vaccines as a component of the complex treatment. The prospects for immunotherapy in neurooncology are discussed.