TREATMENT OPTIONS FOR LOCOREGIONAL RECURRENCES OF ORAL AND OROPHARYNGEAL MUCOSAL SQUAMOUS CELL CARCINOMA

The study included 314 patients with recurrent squamous cell carcinoma of the oral cavity and oropharynx after radical treatment. Patients were divided into groups depending on the timing – patients with early recurrence (n = 162), and late recurrence (n = 152 ), and depending on the type of treatment of recurrent tumors: conservative treatment group (n = 56 ), surgical (n = 235) and combined treatment (n = 23) group. A comparative evaluation of the effectiveness of the treatment of these patients based on the results of treatment, survival rates, the frequency and severity of complications. The conservative therapy of recurrent tumors of the oral cavity if surgical treatment is impossible is effective, especially in cases of late recurrent tumors but only surgical or combined treatment may reach the five-year survival rate in patients with recurrent tumor, cancer of the oral cavity and oropharynx

Efficacy of long-term octreotide therapy of acromegaly as the first-line medical treatment

Acromegaly is a severe neuroendocrine disease characterized by hypersecretion of growth hormone (GH) caused in 95% of cases by pituitary adenoma, which leads to the development of pathology of various organs and systems. The severity of the condition is due not only to the direct effect of somatotropic hormone on the body and the effect of the adenoma on the surrounding structures, but also to the age of the patient and complications associated with the disease. Improvement in treatment methods allows for a personalized approach to patient management, taking into account various aspects of the clinical case. It is important for a specialist to take into account comorbidity in acromegaly, both in terms of pathological disorders and the impact on the patient’s psycho-emotional state. We present a clinical case of successful treatment with somatostatin analogues (ASS) in a patient who is afraid of surgery and has cardiovascular complications of acromegaly. Since the onset of acromegaly, confirmed by an elevated level of insulin-like growth factor-1 (IGF-1) and an endosellar pituitary macroadenoma measuring 11x9.5x8 mm, ASS therapy was initiated in the patient. The choice in favor of conservative treatment was due to a burdened cardiovascular history and the patient’s fear of surgery. Within three years from the start of drug therapy, there was a significant improvement in overall well-being, a tendency to reduce the size of the pituitary adenoma, and biochemical remission was achieved. The clinical case described by us confirms the possibility of successful primary treatment of ASS in a patient with acromegaly, taking into account all individual characteristics

Experiense of treatment with a growth hormone receptor antagonist in patients with hereditary form of acromegaly: clinical cases

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly

CDC20 is regulated by the histone methyltransferase, KMT5A, in castration resistant prostate cancer

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signal- ing are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase depend- ent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting

CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer

The methyltransferase KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis, we have performed a microarray study on a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of the transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and gene ontology analysis revealed that apoptosis and DNA damage signalling were up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase-dependent manner to modulate histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples, further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilised as a biomarker for effective therapeutic targeting

Epidemiological and clinical features of lymphoproliferative diseases in the head and neck region

Background. Lymphomas are a heterogeneous group of the lymphoid and hematopoietic system tumors. Neoplastic process often develops in head and neck area, including the integumentary tissues, orbit, nasal cavity, paranasal sinuses, oral cavity, pharynx, salivary glands, thyroid gland, as well as neck lymph nodes. The difficulties of head and neck lymphomas diagnosis are significant, since very often there is a combined non-tumor pathology. The high heterogeneity of lymphomas in the head and neck area requires structuring knowledge about their epidemiology and clinical manifestations.Objective: to study the epidemiological and clinical features of the head and neck lymphoproliferative diseases, which will lead to an improvement in diagnostic quality of this nosology's.Materials and methods. The frequency of head and neck lymphoproliferative diseases detection was estimated based on the study of epicrisis and clinical data of 174 patients hospitalized at the N.N. Blokhin National Medical Research Center of Oncology in the period from 2000 to 2020.Results. Taking into account the modern clinical and morphological classification of lymphomas of the World Health Organization (2017), information about the features of localization, characteristic signs of extranodal foci and lymph nodes is presented. Detection frequency of various subtypes non-Hodgkin's and Hodgkin's lymphomas were determined on a sufficient cohort of patients.Conclusion. Based on the analysis of clinical and morphological features of head and neck lymphomas, epidemiological and clinical features are described in detail, and differences in the symptoms and clinical manifestations of non-Hodgkin's and Hodgkin's lymphomas with a predominant head and neck involvement are revealed

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ. ДИАГНОСТИКА И ЛЕЧЕНИЕ РАКА РОТОГЛОТКИ

Клинические рекомендации подготовлены на основании материалов научно-практической конференции Проблемной комиссии «Опухоли головы и шеи» Научного совета по злокачественным новообразованиям Отделения медицинских наук Российской академии наук и Министерства здравоохранения РФ, посвященной памяти профессора Александра Ильича Пачеса, «Актуальные вопросы диагностики и лечения рака ротоглотки» (25 июня 2015 г., г. Архангельск).Клинические рекомендации подготовлены на основании материалов научно-практической конференции Проблемной комиссии «Опухоли головы и шеи» Научного совета по злокачественным новообразованиям Отделения медицинских наук Российской академии наук и Министерства здравоохранения РФ, посвященной памяти профессора Александра Ильича Пачеса, «Актуальные вопросы диагностики и лечения рака ротоглотки» (25 июня 2015 г., г. Архангельск)

Molecular mechanism of the TP53-MDM2-AR-AKT signalling network regulation by USP12

The TP53-MDM2-AR-AKT signalling network plays a critical role in the development and progression of prostate cancer. However, the molecular mechanisms regulating this signalling network are not completely defined. By conducting transcriptome analysis, denaturing immunoprecipitations and immunopathology, we demonstrate that the TP53-MDM2-AR-AKT cross-talk is regulated by the deubiquitinating enzyme USP12 in prostate cancer. Our findings explain why USP12 is one of the 12 most commonly overexpressed cancer-associated genes located near an amplified super-enhancer. We find that USP12 deubiquitinates MDM2 and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer. Consequently, USP12 levels are predictive not only of cancer development but also of patient’s therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer