Zaira Spinello  Anna Fregnani  Laura Quotti Tubi  Livio Trentin  Francesco Piazza  Sabrina Manni 《International journal of molecular sciences》2021,22(7)

Disturbance of protein kinase activity may result in dramatic consequences that often lead to cancer development and progression. In tumors of blood origin, both tyrosine kinases and serine/threonine kinases are altered by different types of mutations, critically regulating cancer hallmarks. CK1α and CK2 are highly conserved, ubiquitously expressed and constitutively active pleiotropic kinases, which participate in multiple biological processes. The involvement of these kinases in solid and blood cancers is well documented. CK1α and CK2 are overactive in multiple myeloma, leukemias and lymphomas. Intriguingly, they are not required to the same degree for the viability of normal cells, corroborating the idea of “druggable” kinases. Different to other kinases, mutations on the gene encoding CK1α and CK2 are rare or not reported. Actually, these two kinases are outside the paradigm of oncogene addiction, since cancer cells’ dependency on these proteins resembles the phenomenon of “non-oncogene” addiction. In this review, we will summarize the general features of CK1α and CK2 and the most relevant oncogenic and stress-related signaling nodes, regulated by kinase phosphorylation, that may lead to tumor progression. Finally, we will report the current data, which support the positioning of these two kinases in the therapeutic scene of hematological cancers.  相似文献   

    

Hugo Arasanz  Miren Zuazo  Ana Bocanegra  Luisa Chocarro  Ester Blanco  Maite Martínez  Idoia Morilla  Gonzalo Fernndez  Lucía Teijeira  Pilar Morente  Miriam Echaide  Natalia Castro  Leticia Fernndez  Maider Garnica  Pablo Ramos  David Escors  Grazyna Kochan  Ruth Vera 《International journal of molecular sciences》2021,22(7)

Along with the positioning of immunotherapy as a preferential treatment for a wide variety of neoplasms, a new pattern of response consisting in a sudden acceleration of tumor growth has been described. This phenomenon has received the name of “hyperprogressive disease”, and several definitions have been proposed for its identification, most of them relying on radiological criteria. However, due to the fact that the cellular and molecular mechanisms have not been elucidated yet, there is still some debate regarding whether this fast progression is induced by immunotherapy or only reflects the natural course of some highly aggressive neoplasms. Moreover, contradictory results of trials including patients with different cancer types suggest that both the incidence, the associated factors and the implications regarding prognosis might differ depending on tumor histology. This article intends to review the main publications regarding this matter and critically approach the most controversial aspects.  相似文献   

    

Maria A. Papadaki  Ippokratis Messaritakis  Oraianthi Fiste  John Souglakos  Eleni Politaki  Athanasios Kotsakis  Vassilis Georgoulias  Dimitrios Mavroudis  Sofia Agelaki 《International journal of molecular sciences》2021,22(2)

We herein investigated the detection frequency and clinical relevance of circulating tumor cells (CTCs) in chemotherapy-naïve stage IIIB/IV non-small cell lung cancer (NSCLC), by using the CellSearch and real-time CEACAM5mRNA assays. Blood samples from 43 patients were obtained at different time points during first-line chemotherapy. CellSearch revealed the detection of ≥1 CTCs in 41.9%, 40.9%, and 16.7% of patients at baseline, post-1st, and post-2nd treatment cycle, respectively, and of ≥5 CTCs in 11.6%, 9.1%, and 5.6%, respectively. CEACAM5mRNA+ CTCs were detected in 29.3% and 16% of patients pre- and post-treatment, respectively. The positivity concordance between the two assays was 2.2%. CTC-detection by CellSearch (≥5 CTCs: p = 0.004), CEACAM5mRNA (p = 0.010), or by any assay (p = 0.000) was associated with disease progression. Reduced survival was demonstrated for patients harboring ≥5 CTCs (progression-free survival; PFS: p = 0.000; overall survival; OS: p = 0.009), CEACAM5mRNA+ CTCs (PFS: p = 0.043; OS: p = 0.039), and CTCs by any assay (PFS: p = 0.005; OS: p = 0.006, respectively). CTC-detection by any assay independently predicted for increased risk of relapse (hazard ratio; HR: 3.496; p = 0.001) and death (HR: 2.866; p = 0.008). CellSearch-positivity either pre-, post-1st, or post-2nd cycle, was predictive for shorter PFS (p = 0.036) compared to negativity in all time points. Persistent CEACAM5mRNA-positivity pre- and post-treatment was associated with reduced PFS (p = 0.036) and OS (p = 0.026). In conclusion, CTC detection and monitoring using the CellSearch and CEACAM5mRNA assays provides valuable and complementary clinical information for chemo-naïve advanced or metastatic NSCLC.  相似文献   

    

Roxana Deleanu  Laura Cristina Ceafalan  Anica Dricu 《International journal of molecular sciences》2021,22(24)

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A. Berrezoug;A.S. A Dib;A.H. Belbachir 《Radioprotection》2015,50(4):281-285

In recent years, application of nanoparticles (NPs) in diagnosis and treatment of cancer has been the issue of extensive research. In this study, we investigated the effect of gold nanoparticles (GNPs) in a tumor during X-ray therapy. Our simulation, based on the Monte Carlo method, shows that the GNPs injected into a tumor considerably enhanced the absorbed dose during X-ray therapy, especially in the energy range between 10 keV and 150 keV. This increase in the absorbed dose is due to a combination of increased photoelectric interaction and Auger electron generation from the gold atoms. Furthermore, the absorbed dose in a biological cell is strongly influenced by the size of the GNPs; our results show that the ideal diameter of GNPs should be around 50 nm, and this result was confirmed by several authors. https://doi.org/10.1051/radiopro/2015019  相似文献   

    

F. Benlakhdar;A. S.A. Dib;A. H. Belbachir 《Radioprotection》2016,51(4):279-285

This work is based on a numerical study using the Monte Carlo code Geant4 of an X-ray exposure of a human head containing a tumor at the center. Our principal goal was to investigate the effect of inserting nanomaterials into the tumor on the absorbed dose. Gold is the most popular nanomaterial used in nanomedicine. In our simulation, we also focused on the other nanomaterials platinum, gadolinium and silver. Our results show that gold and platinum increase the absorbed dose in the tumor by up to 55%; the most suitable X-ray energy is between 20 keV and 140 keV. Both of these nanomaterials present the same advantages in X-ray therapy. Moreover, gadolinium increases the absorbed dose by up to 50%, while silver increases the absorbed dose by up to 20%. However, for both of these nanomaterials, the best X-ray energy to use is between 20 keV and 80 keV. https://doi.org/10.1051/radiopro/2016073  相似文献   

    

Ge Gao  Xianbao Sun  Gaolin Liang 《Advanced functional materials》2021,31(25):2100738

Photothermal therapy (PTT), which utilizes near-infrared light-absorbing agents to ablate tumor, has emerged as a highly promising anticancer strategy and received intensive clinical trials in recent years. Mild-temperature PTT, which circumvents the limitations of conventional PTT (e.g., thermoresistance and adverse effects), is emerging and shows great potential in the forthcoming clinical applications. However, mild-temperature PTT without adjuvant therapy is not able to completely eradicate tumors because its therapeutic efficacy is dramatically impaired by its inferior heat intensity. As a result, strategies capable of enhancing the anticancer efficacy of mild-temperature PTT are urgently necessitated, which mainly rely on on-demand fabrication of functionalized nanoagents. In this review, the strategies of nanoagent-promoted mild-temperature PTT are highlighted. Furthermore, challenges and opportunities in this field are rationally proposed, and hopefully people can be encouraged by this promising anticancer therapy.  相似文献   

    

Longfei Tan  Shengping Wang  Ke Xu  Tianlong Liu  Ping Liang  Meng Niu  Changhui Fu  Haibo Shao  Jie Yu  Tengchuang Ma  Xiangling Ren  Hong Li  Jianping Dou  Jun Ren  Xianwei Meng 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(15):2046-2055

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand‐new MoS₂ nanostructure is designed and fabricated, i.e., layered MoS₂ hollow spheres (LMHSs) with strong absorption in near‐infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as‐prepared LMHSs exhibit unique electronic properties comparing with MoS₂ nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX₂ tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor‐targeting delivery and cancer theranostic application.  相似文献   

    

Xihui Gao  Qi Yue  Zining Liu  Mengjing Ke  Xingyu Zhou  Sihan Li  Jianping Zhang  Ren Zhang  Liang Chen  Ying Mao  Cong Li 《Advanced materials (Deerfield Beach, Fla.)》2017,29(21)

Surgical resection is a mainstay in the treatment of malignant brain tumors. Surgeons, however, face great challenges in distinguishing tumor margins due to their infiltrated nature. Here, a pair of gold nanoprobes that enter a brain tumor by crossing the blood–brain barrier is developed. The acidic tumor environment triggers their assembly with the concomitant activation of both magnetic resonance (MR) and surface‐enhanced resonance Raman spectroscopy (SERRS) signals. While the bulky aggregates continuously trap into the tumor interstitium, the intact nanoprobes in normal brain tissue can be transported back into the blood stream in a timely manner. Experimental results show that physiological acidity triggers nanoparticle assembly by forming 3D spherical nanoclusters with remarkable MR and SERRS signal enhancements. The nanoprobes not only preoperatively define orthotopic glioblastoma xenografts by magnetic resonance imaging (MRI) with high sensitivity and durability in vivo, but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner. Microscopy studies verify the precisely demarcated tumor margin marked by the assembled nanoprobes. Taking advantage of the nanoprobes' rapid excretion rate and the extracellular acidification as a hallmark of solid tumors, these nanoprobes are promising in improving brain‐tumor surgical outcome with high specificity, safety, and universality.  相似文献   

    

Changkyu Lee  Ha Shin Hwang  Sungin Lee  Bomi Kim  Jong Oh Kim  Kyung Taek Oh  Eun Seong Lee  Han‐Gon Choi  Yu Seok Youn 《Advanced materials (Deerfield Beach, Fla.)》2017,29(13)

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