HIF-1alpha in lung carcinoma: Histopathological evidence of hypoxia targets in patient biopsies

Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

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“…The hypoxia-inducible factor-1 (HIF-1) is an oxygen-sensitive transcriptional activator and is causally involved in NSCLC [ 77 – 79 ].…”

Section: Resultsmentioning

confidence: 99%

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Huang

Chang

Lin

et al. 2014

BioMed Research International

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“…Hypoxia promotes metastasis in CRC through the activation of the hypoxia inducible transcription factors (HIFs), HIF‐1α, and HIF‐2α, which regulate genes associated with tumor growth, invasion, angiogenesis, glucose metabolism, EMT, and treatment resistance (Ioannou et al, 2015; X. Lu & Kang, 2010). Several studies suggested curcumin and its analogs as reducers of HIF activity in several human tumor cell lines.…”

Section: Role Of Curcumin In Crcmentioning

confidence: 99%

Curcumin and its anti‐colorectal cancer potential: From mechanisms of action to autophagy

Brockmueller,

Ruiz de Porras,

Shakibaei

2024

Phytotherapy Research

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Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis‐resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost‐effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co‐therapeutic agent in CRC.

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“…В литературе имеются данные об увеличенной экспрессии HIF-1α, ГК и CD44v6 в клетках НМКРЛ и их ассоциации с плохим прогнозом заболевания [9][10][11]. Рост уровня биомолекул в опухолевой ткани закономерно сопровождается выходом их из опухолевых клеток в кровь.…”

unclassified

Компоненты оси HIF-1α / рецептор CD44v6 / гиалуроновая кислота в крови пациентов с немелкоклеточным раком легкого. Перспективы использования в диагностике

Мурашко¹,

Таганович²,

Ковганко³

2022

Евразийский Онкологический Журнал

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Введение. Немелкоклеточный рак легкого (НМКРЛ) занимает второе место в структуре смертности вследствие онкологических заболеваний в Республике Беларусь. Он подразделяется на два основных гистологических подтипа: аденокарциному (АК) и плоскоклеточный рак (ПКРЛ). Поздняя диагностика существенно ухудшает прогноз течения этого заболевания, в связи с чем существует потребность в поиске информативных биомаркеров, позволяющих судить о распространенности опухолевого процесса, особенно на ранних стадиях НМКРЛ. Цель. Изучить уровень CD44v6, HIF-1α и гиалуроновой кислоты (ГК) в периферической крови пациентов с НМКРЛ с тем, чтобы оценить целесообразность его использования в диагностике НМКРЛ.Материалы и методы. Материалом служила кровь 107 пациентов с ПКРЛ, 90 пациентов с АК, 14 человек с гамартомой легкого и 40 здоровых людей. Концентрацию ГК и HIF-1α в сыворотке крови определяли методом иммуноферментного анализа. Относительное количество клеток лейкоцитарного ряда, снабженных рецептором CD44v6, и плотность его расположения в них (MFI) измеряли методом проточной цитометрии.Результаты. Уровень ГК, HIF-1α, доля моноцитов, содержащих CD44v6, и плотность расположения этого рецептора в гранулоцитах и лимфоцитах крови пациентов с АК и ПКРЛ значительно превышают таковые у здоровых людей и пациентов с гамартомой. Концентрация ГК в сыворотке крови выше у пациентов с большим размером опухоли, наличием метастазов в регионарные лимфоузлы и внутренние органы вне зависимости от гистологического типа НМКРЛ. Плотность расположения CD44v6 в лимфоцитах выше у пациентов с большим (>5 см) размером опухоли и метастазами во внутренние органы (М1) при обоих гистологических типах заболевания, а аналогичный показатель в гранулоцитах существенно возрастает при наличии регионарных метастазов НМКРЛ (N1–3). Концентрация ГК имеет коррелятивную связь со стадиями АК и ПКРЛ.Измерение концентрации ГК в сыворотке крови пациентов позволяет дифференцировать I и II стадии НМКРЛ с чувствительностью 72,2% и специфичностью 99,2% для рассчитанного порогового значения, а при выявлении III–IV стадий чувствительность составила 67,6%, специфичность – 81,2%. Introduction. Non-small cell lung cancer (NSCLC) takes the second place in the structure of cancer morbidity in Belarus. It is classified into two main histological types: adenocarcinoma (AC) and squamous cell carcinoma (SCC). Late diagnosis significantly worsens the prognosis of this disease. That’s why there is the need to search for available and informative biomarkers that let to assess the prevalence of NSCLC, especially its early stages.Purpose. To study the level of CD44v6, HIF-1α and hyaluronic acid (HA) in the peripheral blood of patients with NSCLC in order to assess the feasibility of its use in diagnostics of NSCLC.Materials and methods. There were studied the blood samples of 107 patients with SCC, 90patients with AC, 14 patients with lung hamartoma, and 40 healthy people. HIF-1α and HA serum levels were determined with ELISA. The relative number of leukocytes supplied with CD44v6 and its density in the cells (MFI) were measured with flow cytometry.Results. HIF-1α and HA serum levels, relative number of monocytes and granulocytes, and MFI CD44v6 in granulocytes and lymphocytes of the blood of patients with AC and SCC are significantly higher than in healthy people and patients with lung hamartoma. HA serum level is higher in both AC and SCC patients with bigger tumor size (T > 5 cm), regional lymph node (N1–3) and distant metastases (M1). MFI CD44v6 in lymphocytes increases in both histological types of NSCLC in patients with T > 5 cm and distant metastases. At the same time, MFI CD44v6 in granulocytes is higher in AC and SCC patients with regional lymph node metastases. HA serum level has a medium strong correlation with AC and SCC TNM stages.The cutoff value of HA serum level allows to differentiate the stages I and II of the NSCLC with 72.2% of diagnostic sensitivity and 99.2% of specificity. The same indicator can be used to determine the advanced stages of NSCLC (67.6% of sensitivity, 81.2% of specificity).

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HIF-1alpha in lung carcinoma: Histopathological evidence of hypoxia targets in patient biopsies

Cited by 4 publications

References 50 publications

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Curcumin and its anti‐colorectal cancer potential: From mechanisms of action to autophagy

Компоненты оси HIF-1α / рецептор CD44v6 / гиалуроновая кислота в крови пациентов с немелкоклеточным раком легкого. Перспективы использования в диагностике

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