Directed Therapies in Lung Cancer: New Hope?

Lamelas, Isaura Parente; Arca, José Abal; Pérez, José Luis Fírvida

doi:10.1016/j.arbr.2012.07.003

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…Lung cancer (LC) imposes a great threat to human health because of its high morbidity and mortality. [1] According to incomplete statistics, LC-related deaths account for nearly 29% of total cancer-related deaths annually. [2][3][4] The 5-year survival rate of LC patients is less than 15%.…”

Section: Introductionmentioning

confidence: 99%

SIRT3 acts as a novel biomarker for the diagnosis of lung cancer

Feng¹,

Gu²,

Li³

et al. 2021

Medicine

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Lung cancer (LC) is a prevalent malignancy worldwide with increased morbidity and mortality. Mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-3 (SIRT3) has been reported to be involved in tumorigenesis. In this retrospective study, we measured the expression and diagnostic value of SIRT3 in LC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure serum SIRT3 mRNA level in 150 LC patients and 52 healthy volunteers. SIRT3 protein level was detected using western blot for 84 pairs of LC and adjacent normal tissues. The association of SIRT3 mRNA level with clinical parameters of LC patients was estimated via chi-square test. Receiver operating characteristic curve (ROC) was plotted to evaluate the diagnostic performance of serum SIRT3 in LC patients. SIRT3 mRNA and protein levels were significantly decreased in LC tissues and serum samples, compared with corresponding controls ( P < .05). Moreover, the expression of SIRT3 mRNA was negatively associated with tumor size ( P = .002), tumor node metastasis stage ( P < .001), and metastasis ( P < .001). ROC curve demonstrated that serum SIRT3 could distinguish LC patients from healthy individuals, with an area under the curve of 0.918. The optimal cutoff value was 3.12, reaching a sensitivity of 86.4%, and a specificity of 94%. SIRT3 expression is significantly down-regulated in LC serum and tissues. SIRT3 may be employed as a promising biomarker in the early diagnosis of LC.

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Section: Introductionmentioning

confidence: 99%

SIRT3 acts as a novel biomarker for the diagnosis of lung cancer

Feng¹,

Gu²,

Li³

et al. 2021

Medicine

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“…Так, идентифицирован ряд внутриклеточных сигнальных путей, которые могут иметь определяющее значение в лечении рака легких. Среди таких факторов особую прогностическую роль играют фактор роста гепатоцитов (c-MET/HGF) и его рецептор, b-тубулин класса 3 (TUBB3), рецепторная тирозинкиназа анапластической лимфомы (ALK) и некоторые другие [3,4].…”

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“…Фармакотерапевтические подходы, базирующиеся на определенных молекулярных механизмах развития опухоли, определяют сущность направленной, таргетной или персонализированной терапии. Подобные химиотерапевтические протоколы воздействуют на конкретные биологические мишени и существенно повышают продолжительность жизни, особенно у пациентов, которым не показано хирургическое лечение [4]. В исследованиях на культуре опухолевых клеток показана перспективность использования соединений -производных аминохромена -для химиотерапии ряда злокачественных новообразований эпителиального происхождения [5].…”

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Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model

Samishina¹,

Dudina

Блинова

et al. 2019

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Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeﬁcient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic eﬀects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic eﬀect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established eﬀect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is conﬁrmed by the absence of diﬀerences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more eﬀectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes.

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