Ulykbek Kairov

Background/Objectives: Alzheimer’s disease (AD) has a substantial genetic component, yet Central Asian populations remain markedly underrepresented in genomic studies of the disease. Methods: to address this gap, we generated array-based genotype data using an immune-focused genotyping platform from a Kazakh AD case–control cohort and performed an exploratory association analysis. Following quality control, 180 individuals of Kazakh ancestry, including 92 individuals with AD and 88 cognitively normal controls, were analyzed. Population structure was assessed using principal component analysis, and association testing was performed using covariate-adjusted logistic regression under an additive model (primary analysis), with case–control tests under several genetic models as secondary analyses. Results: no variant reached study-wide significance; however, several exploratory association signals (p < 1 × 10⁻⁴) were identified, including variants on chromosome 9p24 and in ADARB2, MAST4, and ADAM23, which remained nominally associated after adjustment for sex, age, and principal components. In addition, APOE ε4 carrier status was evaluated in cases and controls. The proportion of APOE ε4 carriers was numerically higher among individuals with AD than among controls (40.7% vs. 26.6%), although the difference did not reach statistical significance (p = 0.074). These findings should be considered hypothesis-generating and require replication in larger independent cohorts. Conclusions: this study provides one of the first immune-focused array-based genotype datasets for AD in a Central Asian population. The publicly available genotype data and association results provide a foundation for future replication, meta-analysis, and comparative population-genetic studies of AD across diverse ancestry groups.

Background/Objectives: Genetic factors are known to influence overall immune vulnerability to diseases, such as tuberculosis (TB); however, isolating the genetic component can be challenging as social and environmental causes, such as smoking, alcohol consumption, and unemployment, also drive disease risk. To reduce heterogeneity related to these factors, we performed a targeted immunogenetic association study of TB susceptibility in a Kazakh case–control cohort selected among individuals without the typical socioeconomic and nutritional risk factors linked to TB. Methods: We performed genotyping using an immune-focused targeted array; after quality control at sample and variant level, removal of ancestry-based outliers, and adjustment for population stratification, the final dataset included 164 participants (84 cases, 80 controls) and 181,595 variants. We performed four complementary analyses: single-variant association testing using logistic regression with Firth correction where required adjusted for sex and genetic ancestry, gene-based aggregation testing, functional annotation, and polygenic risk scoring using existing multi-ancestry TB genetic resources. Results: While no variant reached formal significance, the top nominal signal, rs1560036 (OR = 2.98, p = 2.4 × 10⁻⁵), lies within CPLX2, which ranked among the top genes in gene-based analysis, a result driven largely by the same variant. A nominally associated variant in the classical MHC region, rs9263600, is separately reported in GTEx as a cis-eQTL for HLA-B and HLA-C. Similarly, polygenic risk scores showed directionally consistent but statistically non-significant associations with case status (Asia-base AUC = 0.560; Europe-base AUC = 0.537). Conclusions: Although our study was not adequately powered to detect small-to-moderate genetic effects, it offers an important perspective on TB genetics in a population underrepresented in existing research. These findings provide an openly available dataset and candidate signals for replication in larger, independent cohorts.

Background. Secondary upper limb lymphedema is a complication of multimodal treatment for malignant neoplasms associated with damage to the regional lymphatic system. Indocyanine green (ICG) fluorescence lymphography enables real-time visualization of superficial lymphatic vessels and assessment of lymphatic drainage patterns. However, data on fluorescence patterns in secondary lymphedema of different oncological etiologies and their clinical significance remain limited. Objective. To evaluate the diagnostic potential of ICG fluorescence lymphography for detecting and characterizing lymphatic drainage abnormalities in female patients with secondary upper limb lymphedema following multimodal treatment for malignant neoplasms. Materials and Methods. A case series of 10 female patients with secondary upper limb lymphedema following treatment for breast cancer (n = 7), melanoma (n = 2), and cutaneous squamous cell carcinoma (n = 1) was analyzed. The duration of lymphedema before examination ranged from 3 months to 2–3 years. All patients underwent ICG fluorescence lymphography. Results. Fluorescence lymphography revealed four lymphatic drainage patterns: a linear pattern and three types of dermal backflow, namely splash, stardust, and diffuse patterns. The characteristics and extent of fluorescence abnormalities reflected the underlying alterations in lymphatic drainage. Visualization of preserved lymphatic collectors enabled identification of their anatomical location and potential sites for lymphovenous anastomosis. Conclusion. ICG fluorescence lymphography enabled characterization of lymphatic drainage abnormalities and visualization of preserved superficial lymphatic collectors. The findings demonstrated the potential utility of this technique for assessing lymphatic dysfunction, individualizing treatment strategies, and facilitating preoperative planning of lymphovenous anastomosis.

Background: Medullary thyroid carcinoma is a rare neuroendocrine malignancy characterized by variable clinical behavior, a risk of regional and distant metastasis, and limited systemic treatment options in advanced disease. Vandetanib is one of the therapeutic options for progressive unresectable locally advanced and metastatic medullary thyroid carcinoma; however, published evidence on its use in real-world clinical practice in Kazakhstan remains limited. Objective: To describe the use of vandetanib in a patient with metastatic medullary thyroid carcinoma in real-world clinical practice in Kazakhstan and to analyze the long-term disease course, treatment monitoring, and multidisciplinary management. Materials and methods: A retrospective analysis of a clinical case of a patient with medullary thyroid carcinoma was performed based on medical history, hospital discharge summaries, surgical treatment records, laboratory findings, computed tomography data, and clinical documentation collected over more than six years of follow-up. Tumor progression, distant metastatic spread, functional status, comorbidities, and features of monitoring during vandetanib therapy were assessed. Results: The patient was diagnosed with medullary thyroid carcinoma and underwent surgical treatment. During long-term follow-up, disease progression with metastatic spread involving the lungs, intrathoracic structures, and bone tissue was documented. At the stage of disseminated disease, targeted therapy with vandetanib was initiated. Patient management required regular laboratory, imaging, and cardiac monitoring because of significant comorbidity, the risk of adverse events, and the need for safety surveillance during treatment. Conclusion: This clinical case demonstrates the feasibility of using vandetanib in a patient with metastatic medullary thyroid carcinoma in real-world clinical practice in Kazakhstan. Treatment with vandetanib requires a personalized approach, careful patient selection, multidisciplinary support, and regular safety monitoring, particularly in patients with cardiovascular and metabolic comorbidities. Reporting such cases is important for expanding national experience with targeted therapy in rare thyroid malignancies.

Background: Addressing the therapeutic challenges associated with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutant cancers remains a significant focus in oncology. The combined intravenous administration of the D-isomer of vitamin C (D-VC) (dextro-rotatory isomer of ascorbic acid) and arsenic trioxide (ATO) is proposed as a potential approach for achieving an anti-tumor effect in Colorectal cancer (CRC) with KRAS-mutant tumor cells. ATO enhances the oxidative effect of vitamin C (VC), and the combination of both drugs provides effective eradication of KRAS-mutant cancer cells. A potent synergistic effect of the VC and ATO combination has been observed about KRAS-mutant cancer cells. Purpose: This clinical trial aims to assess the tolerability and safety of intravenous administration of D-VC along with ATO in patients with advanced/metastatic malignancies who have exhausted standard therapy. Methods and Patients: This single-center Phase I clinical trial evaluated the tolerability and safety of D-VC when administered intravenously alone or in sequential administration with ATO. The target group for the Phase I exploratory clinical trial includes 10 patients with advanced/metastatic malignant neoplasms who have exhausted standard therapy. Results: The administration of the drug followed the treatment regimen according to the ap-proved study protocol. After a single intravenous infusion of D-VC in escalating doses of 0.05 g/kg - 0.1 g/kg - 0.15 g/kg - 0.3 g/kg all patients felt satisfactory, and no subjective intolerance to the investigational drug was reported. The main functional and laboratory parameters remained within normal values recorded at the start of the study. The maximum tolerated dose of D-VC was determined to be 0.3 g/kg, and this dose was chosen as the baseline for the second stage of the study, where D-VC (0.3 g/kg) was administered alongside ATO (0.15 mg/kg). Conclusions: Our findings showed favorable safety and well-tolerated profiles and provided the recommended dose for high-dose D-VC in combination with АТО.

Метастатическое поражение позвоночника является одним из наиболее тяжелых осложнений распространенного рака молочной железы и сопровождается выраженным хроническим болевым синдромом, снижением функциональной активности и ухудшением качества жизни пациенток. Современный подход к лечению включает комплексное применение локальных, системных и поддерживающих методов терапии, однако оценка эффективности отдельных компонентов мультимодального лечения остается актуальной задачей. Цель исследования: оценить динамику болевого синдрома у пациенток с метастатическим поражением позвоночника при раке молочной железы после проведения стандартного и расширенного мультимодального лечения. Методы. Проведено проспективное открытое контролируемое нерандомизированное когортное исследование с параллельным сравнением двух групп. В исследование включены 75 пациенток с гистологически подтвержденным раком молочной железы IV стадии и радиологически верифицированными метастазами позвоночника. Все пациентки получали стандартное мультимодальное лечение, включавшее чрескожную вертебропластику, лучевую терапию и антиостеорезорбтивную терапию. В основной группе (n=30) дополнительно применялась нутритивная поддержка сублимированным кобыльим молоком - саумал, в контрольной группе (n=45) дополнительная нутритивная поддержка не применялась. Интенсивность болевого синдрома оценивали по визуально-аналоговой шкале (ВАШ) до лечения, через 2 недели, 1, 3 и 6 месяцев после начала терапии. Результаты. Исходный уровень болевого синдрома был сопоставим между группами: показатель ВАШ составил 7,37±0,56 балла в основной группе и 7,40±0,62 балла в контрольной группе (p=0,927). В процессе наблюдения в обеих группах отмечено статистически значимое снижение интенсивности боли относительно исходного уровня (p<0,001). Через 6 месяцев показатель ВАШ составил 3,23 ± 0,73 балла в основной группе и 3,16 ± 0,64 балла в контрольной группе. Различий между группами по динамике болевого синдрома выявлено не было (p=0,761). Снижение интенсивности боли более чем на 2 балла достигалось уже через 2 недели после начала лечения и сохранялось на протяжении всего периода наблюдения. Выводы. Стандартное мультимодальное лечение пациенток с метастатическим поражением позвоночника при раке молочной железы обеспечивает выраженное и устойчивое снижение болевого синдрома в течение шестимесячного периода наблюдения. Дополнительное включение саумал в лечебный комплекс не продемонстрировало статистически значимого преимущества по показателям ВАШ, однако не изменяло положительный эффект базового мультимодального подхода.

Казахстан находится на переломном этапе развития биоинформатики. Впервые страна объединяет три условия, которые эта дисциплина требует в полном масштабе, современные мощности секвенирования, значительные высокопроизводительные вычисления и быстро растущий резерв вычислительных кадров. Национальная лаборатория Астана при Назарбаев Университете стала первым и на сегодняшний день наиболее развитым центром биоинформатики и геномики в регионе, создав первые геномные референсные ресурсы для казахстанской популяции и распространив геномные методы на сферу общественного здравоохранения. Национальные инвестиции в суперкомпьютеры и искусственный интеллект вместе с быстро растущим сектором ИТ-образования создают редкую возможность построить биоинформатику, изначально опирающуюся на ИИ. Тем не менее перед областью стоят серьёзные вызовы: аналитическое «узкое место», нехватка междисциплинарных специалистов, незрелое управление данными и что наиболее существенно модель финансирования, при которой зарплаты ключевых специалистов и руководителей лабораторий, а также обновление инфраструктуры почти полностью зависят от конкурсных грантов. В этой редакционной статье утверждается, что решающим шагом является устойчивое регулярное базовое финансирование основной биоинформатической инфраструктуры и кадров, дополненное целевой подготовкой специалистов, грамотным управлением данными и региональным сотрудничеством, чтобы достигнутые успехи превратились в долговременный национальный потенциал, а не оставались зависимыми от очередного грантового цикла.

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