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1.
Mol Biol Rep ; 51(1): 90, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194158

RESUMO

BACKGROUND: CDC25B, as a member of the cell cycle regulating protein family, is located in the cytoplasm and is involved in the transition of the cell cycle and mitosis. CDC25B is highly expressed in various tumors and is a newly discovered oncogene. This study aimed to investigate the impact of CDC25B on mitoxantrone resistance in stomach adenocarcinoma (STAD) and its possible mechanisms. METHODS: This study analyzed the expression of CDC25B and its potential transcription factor E2F3 in STAD, as well as the IC50 values of tumor tissues by bioinformatics analysis. Expression levels of CDC25B and E2F3 in STAD cells were measured by qRT-PCR. MTT was utilized to evaluate cell viability and IC50 values of STAD cells, and comet assay was utilized to analyze the level of DNA damage in STAD cells. Western blot was used to analyze the expression of DNA damage-related proteins. The targeting relationship between E2F3 and CDC25B was validated by dual-luciferase and ChIP assays. RESULTS: Bioinformatics analysis and molecular experiments showed that CDC25B and E2F3 were highly expressed in STAD, and CDC25B was enriched in the mismatch repair and nucleotide excision repair pathways. The IC50 values of tumor tissues with high expression of CDC25B were relatively high. Dual-luciferase and ChIP assays confirmed that CDC25B could be transcriptionally activated by E2F3. Cell experiments revealed that CDC25B promoted mitoxantrone resistance in STAD cells by regulating DNA damage. Further research found that low expression of E2F3 inhibited mitoxantrone resistance in STAD cells by DNA damage, but overexpression of CDC25B reversed the impact of E2F3 knockdown on mitoxantrone resistance in STAD cells. CONCLUSION: This study confirmed a novel mechanism by which E2F3/CDC25B mediated DNA damage to promote mitoxantrone resistance in STAD cells, providing a new therapeutic target for STAD treatment.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Mitoxantrona/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Dano ao DNA , Mitose , Luciferases , Fator de Transcrição E2F3 , Fosfatases cdc25/genética
2.
Biochem Genet ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981987

RESUMO

Gastric cancer (GC) is a health problem that concerns people around the world. CDC25B is an essential cell cycle regulatory factor that is overexpressed in a variety of tumor cells. CDC25B plays a vital part in the progression and proliferation of malignant tumors. However, it is not yet clear that how CDC25B affects the stemness of GC cells. The study used bioinformatics to detect the expression of E2F1 and CDC25B in GC tissues and their correlation, as well as pathways enriched by CDC25B. We detected the expression of E2F1 and CDC25B in GC cell lines using quantitative reverse transcription polymerase chain reaction and tested the combination relationship between E2F1 and CDC25B using chromatin immunoprecipitation (ChIP) and dual-luciferase assays. We measured cell viability using CCK-8 assay, evaluated sphere-forming efficiency using sphere formation assay, and determined cell proliferation ability using colony formation assay. We also analyzed the expression of stemness markers and MAPK pathway-related proteins using western blot. In GC tissues and cells, CDC25B was upregulated. Silencing CDC25B could affect the MAPK pathway, thereby repressing the proliferation and stemness of GC cells. As predicted by bioinformatics, CDC25B had an upstream transcription factor, E2F1, which also had a high expression level in GC. Dual-luciferase and ChIP assays confirmed the combination relationship between the two. Rescue experiments uncovered that overexpression of CDC25B could reverse the impact induced by E2F1 knockdown on proliferation and stemness of cells. In conclusion, E2F1 could activate CDC25B transcription to regulate the MAPK pathway and enhance the proliferation and stemness of GC cells. We revealed a potential regulatory pathway of stemness of GC cells that was mediated by CDC25B, providing new ideas for improving and innovating GC treatment.

3.
J Nanobiotechnology ; 19(1): 423, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915901

RESUMO

Despite the exciting breakthroughs in medical technology, cancer still accounts for one of the principle triggers of death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement in cancer therapy with gigantic application potential because of their ability in achieving precise and controlled drug release, elevating drug solubility and reducing adverse effects. Carbon nanotubes (CNTs), one of the most promising carbon-related nanomaterials, have already achieved much success in biomedical field. Due to their excellent optical property, thermal and electronic conductivity, easy functionalization ability and high drug loading capacity, CNTs can be applied in a multifunctional way for cancer treatment and diagnosis. In this review, we will give an overview of the recent progress of CNT-based drug delivery systems in cancer theranostics, which emphasizes their targetability to intracellular components of tumor cells and extracellular elements in tumor microenvironment. Moreover, a detailed introduction on how CNTs penetrate inside the tumor cells to reach their sites of action and achieve the therapeutic effects, as well as their diagnostic applications will be highlighted.


Assuntos
Nanotubos de Carbono/química , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/uso terapêutico , Microambiente Tumoral
4.
Pharmaceutics ; 16(7)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39065636

RESUMO

Immunotherapy has been a research hotspot due to its low side effects, long-lasting efficacy, and wide anti-tumor spectrum. Recently, NK cell-based immunotherapy has gained broad attention for its unique immunological character of tumor identification and eradication and low risk of graft-versus-host disease and cytokine storm. With the cooperation of a drug delivery system (DDS), NK cells activate tumoricidal activity by adjusting the balance of the activating and inhibitory signals on their surface after drug-loaded DDS administration. Moreover, NK cells or NK-derived exosomes can also be applied as drug carriers for distinct modification to promote NK activation and exert anti-tumor effects. In this review, we first introduce the source and classification of NK cells and describe the common activating and inhibitory receptors on their surface. Then, we summarize the strategies for activating NK cells in vivo through various DDSs. Finally, the application prospects of NK cells in tumor immunotherapy are also discussed.

5.
Adv Sci (Weinh) ; : e2406985, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324577

RESUMO

Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti-inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti-obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro-inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate-linking P3 peptide-modified HA (P3-HA), an enhanced anti-obesity effect is obtained by dual-targeting of P3 and HA, and HA-mediated CD44 poly-clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3-HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti-obesity therapies.

6.
Biomater Sci ; 12(1): 164-175, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37947455

RESUMO

Chemoimmunotherapy is a promising strategy in tumor treatments. In this study, immunogenic dead cells were engineered by the sequential treatment of live tumor cells with ultraviolet (UV) irradiation and cryo-shocking. The dead cells could serve as a lung-targeting vehicle and tumor vaccine after differential loading of the chemo-drug 10-hydroxycamptothecin (HCPT) and immune adjuvant Quillaja saponin-21 (QS-21) via physical absorption and chemical conjugation, respectively. After intravenous administration, the dead cells could be trapped in pulmonary capillaries and could fast release HCPT to enhance the drug accumulation in local tissues. Further, the immunogenic dead cells elicited antitumor immune responses together with the conjugated adjuvant QS-21 to achieve the elimination and long-term surveillance of tumor cells. In a lung tumor-bearing mice model, this drug-delivery system achieved synergistic antitumor efficacy and prolonged the survival of mice.


Assuntos
Antineoplásicos , Vacinas Anticâncer , Camundongos , Animais , Linhagem Celular Tumoral , Pulmão , Vacinação
7.
Cancer Commun (Lond) ; 42(2): 141-163, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35001556

RESUMO

Phototherapy and immunotherapy in combination is regarded as the ideal therapeutic modality to treat both primary and metastatic tumors. Immunotherapy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted elimination. Phototherapy destroys the primary tumors by light irradiation, which induces a series of immune responses through triggering immunogenic cancer cell death. Therefore, when integrating immunotherapy with phototherapy, a novel anti-cancer strategy called photoimmunotherapy (PIT) is emerging. This synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations, opening a new era for the current anti-cancer therapy. Recently, the advancement of nanomaterials affords a platform for PIT. From all these nanomaterials, inorganic nanomaterials stand out as ideal mediators in PIT due to their unique physiochemical properties. Inorganic nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug-loading capacity but also function as photothermal agents or photosensitizers in phototherapy because of their great optical characteristics. In this review, the recent advances of multifunctional inorganic nanomaterial-mediated drug delivery and their contributions to cancer PIT will be highlighted.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Imunoterapia , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia
8.
Appl Biochem Biotechnol ; 194(12): 6255-6269, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35904674

RESUMO

Progression, prognosis, and therapeutic strategy of stomach adenocarcinoma (STAD) have a close connection with tumor microenvironment (TME). Thus, it is pivotal to delve into the TME and immune-related genes, which may bring possibilities for improving patient's prognosis. TCGA-STAD dataset was analyzed to acquire differentially expressed lncRNAs in tumor samples, which were overlapped with the immune-related lncRNA datasets in the ImmLnc database. Twenty-six lncRNAs related to STAD immunity and patient's prognosis were acquired by univariate Cox analysis. Following lncRNA expression patterns, STAD samples could be classified into two clusters with completely different immune patterns. We performed multivariate Cox regression analysis on lncRNAs to identify 7-feature lncRNAs and constructed a corresponding prognostic model. The model validity was verified by survival analysis and ROC curve in validation and training sets. To explore connection between model and TME and tumor drug resistance, this study analyzed differences in immune cell infiltration between samples from high- and low-risk groups and then revealed immune cells follicular helper with significant differences in tumor tissue infiltration. Analysis of resistance to chemotherapeutic drugs revealed that samples in the high-risk group had resistance to cisplatin, doxorubicin, bleomycin, and gemcitabine. Through univariate and multivariate Cox analyses, we manifested that risk score could be an independent prognostic factor. Combining risk score and clinical factors, a nomogram was constructed to accurately predict patient's prognosis. This model can effectively predict prognosis, TME, and drug resistance of STAD patients, which may provide a reference for tumor development evaluation and precise treatment for clinical STAD.


Assuntos
Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Prognóstico , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Cisplatino , Estômago , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Microambiente Tumoral/genética
9.
Biomater Sci ; 10(9): 2370-2383, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35383799

RESUMO

A combination of photothermal therapy (PTT) and chemotherapy is an emerging therapeutic strategy with promising clinical prospects in cancer treatment. Despite the huge progress achieved in the past years, a number of obstacles still hamper the therapeutic efficacy of this synergistic modality such as uneven heat distribution, lack of targetability of anti-cancer agents and dosage-related side effects. Thus, developing a nanoplatform for targeted drug delivery against cancer is of great necessity. Herein, a lipid-polymer hybrid nanosystem (LP/ID) based on polyethyleneimine (PEI)-lecithin-polyethylene glycol (PEG) was fabricated to co-load indocyanine green (ICG) and dichloroacetate (DCA) for combined photothermal/chemotherapy. DCA and ICG were linked to the PEI backbone to form a dense hydrophobic core through amide bonds and electrostatic interactions, which increased the payload of DCA and ICG as well as achieved enzyme-responsive drug release because of the overexpressed amidase in tumor cells. Lecithin and DSPE-PEG2000 self-assembled around the hydrophobic complexes to obtain prolonged blood circulation and attenuated systemic toxicity of the hybrid nanosystem. The prepared LP/ID exhibited favourable stability in a physiological environment, good tumor imaging properties, and satisfactory photothermal/chemotherapeutic performance. Moreover, LP/ID could also enhance the cellular uptake and tumor retention capacity in comparison with free drug administration. Notably, by co-loading two therapeutic agents with different anti-cancer mechanisms, an obvious inhibitory effect on tumor growth was observed with negligible damage to normal tissues and organs because of the synergistic photothermal/chemotherapy effect, indicating the great potential of LP/ID as a robust nanoplatform for cancer treatment.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina/química , Hipertermia Induzida/métodos , Verde de Indocianina/química , Lecitinas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Terapia Fototérmica , Polietilenoimina , Polímeros
10.
Theranostics ; 12(5): 2290-2321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265211

RESUMO

Despite the encouraging breakthroughs in medical development, cancer remains one of the principle causes of death and threatens human health around the world. Conventional treatment strategies often kill cancer cells at the expense of serious adverse effects or great pain, which yet is not able to achieve an effective cure. Therefore, it is urgent to seek for other novel anticancer approaches to improve the survival rate and life quality of cancer patients. During the past decades, nanotechnology has made tremendous progress in cancer therapy due to many advantages such as targeted drug delivery, decreased dosage-related adverse effects and prolonged drug circulation time. In the context of nanomedicine, carbon nanomaterials occupy very significant positions. Owing to their innate outstanding optical, thermal, electronic, and mechanic features, easy functionalization possibility and large surface for drug loading, carbon nanomaterials serve as not only drug carriers, but also multifunctional platforms to combine with diverse treatment and diagnosis modalities against cancer. Therefore, developing more carbon-based nanoplatforms plays a critical role in cancer theranostics and an update overview that summarizes the recent achievement of carbon nanomaterial-mediated anticancer theranostic approaches is of necessity. In this review, five typical and widely investigated carbon nanomaterials including graphene, graphdiyne, fullerene, carbon nanotubes and carbon quantum dots are introduced in detail from the aspect of treatment strategies based on both cancer cells and tumor microenvironment-involved therapeutic targets. Meanwhile, modern diagnostic methods and clinical translatability of carbon nanomaterials will be highlighted as well.


Assuntos
Nanoestruturas , Nanotubos de Carbono , Neoplasias , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Microambiente Tumoral
11.
Front Nutr ; 8: 664940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017850

RESUMO

Purpose: Vitamin D deficiency is a common scenario in critically ill patients and has been proven to be associated with poor outcomes. However, the effect of vitamin D supplementation for critically ill patients remains controversial. Thus, we conducted a meta-analysis to evaluate the effect of vitamin D supplementation among critically ill patients. Methods: Electronic databases PubMed, Embase, Scopus, and the Cochrane Library were searched for eligible randomized controlled trials between 2000 and January 2021. The primary outcome was overall mortality, and the secondary ones were the length of intensive care unit stay, the length of hospital stay, as well as the duration of mechanical ventilation. Subgroup analyses were performed to explore the treatment effect by type of admission, route of administration, dose of supplemented vitamin D, and the degree of vitamin D deficiency. Results: A total of 14 studies involving 2,324 patients were finally included. No effect on overall mortality was found between vitamin D supplementation and control group [odds ratio (OR), 0.73; 95% CI, 0.52-1.03; I 2 = 28%]. The vitamin D supplementation reduced the length of intensive care unit stay [mean difference (MD), -2.25; 95% CI, -4.07 to -0.44, I 2 = 71%] and duration of mechanical ventilation (MD, -3.47; 95% CI, -6.37 to -0.57, I 2 = 88%). In the subgroup analyses, the vitamin D supplementation for surgical patients (OR, 0.67; 95% CI, 0.47-0.94; I 2 = 0%) or through parenteral way (OR, 0.42; 95% CI, 0.22-0.82, I 2 = 0%) was associated with reduced mortality. Conclusion: In critically ill patients, the supplementation of vitamin D has no effect on overall mortality compared to placebo but may decrease the length of intensive care unit stay and mechanical ventilation. Further trials are necessary to confirm our findings.

12.
Pharmaceutics ; 13(12)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34959425

RESUMO

The combinational application of photothermal therapy (PTT), chemotherapy, and nanotechnology is a booming therapeutic strategy for cancer treatment. Multi-walled carbon nanotube (MWNT) is often utilized as drug carrier in biomedical fields with excellent photothermal properties, and indocyanine green (ICG) is a near-infrared (NIR) dye approved by FDA. In addition, ICG is also a photothermal agent that can strongly absorb light energy for tumor ablation. Herein, we explored a synergistic strategy by connecting MWNT and a kind of ICG derivate ICG-NH2 through hyaluronic acid (HA) that possesses CD44 receptor targeting ability, which largely enhanced the PTT effect of both MWNT and ICG-NH2. To realize the synergistic therapeutic effect of chemotherapy and phototherapy, doxorubicin (DOX) was attached on the wall of MWNT via π-π interaction to obtain the final MWNT-HA-ICG/DOX nanocomplexes. Both in vitro and in vivo experiments verified the great therapeutic efficacy of MWNT-HA-ICG/DOX nanocomplexes, which was characterized by improved photothermal performance, strengthened cytotoxicity, and elevated tumor growth inhibition based on MCF-7 tumor models. Therefore, this synergistic strategy we report here might offer a new idea with promising application prospect for cancer treatment.

13.
Pharmaceutics ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34575419

RESUMO

Black phosphorus (BP) is one of the emerging versatile nanomaterials with outstanding biocompatibility and biodegradability, exhibiting great potential as a promising inorganic nanomaterial in the biomedical field. BP nanomaterials possess excellent ability for valid bio-conjugation and molecular loading in anticancer therapy. Generally, BP nanomaterials can be classified into BP nanosheets (BPNSs) and BP quantum dots (BPQDs), both of which can be synthesized through various preparation routes. In addition, BP nanomaterials can be applied as photothermal agents (PTA) for the photothermal therapy (PTT) due to their high photothermal conversion efficiency and larger extinction coefficients. The generated local hyperpyrexia leads to thermal elimination of tumor. Besides, BP nanomaterials are capable of producing singlet oxygen, which enable its application as a photosensitizer for photodynamic therapy (PDT). Moreover, BP nanomaterials can be oxidized and degraded to nontoxic phosphonates and phosphate under physiological conditions, improving their safety as a nano drug carrier in cancer therapy. Recently, it has been reported that BP-based PTT is capable of activating immune responses and alleviating the immunosuppressive tumor microenvironment by detection of T lymphocytes and various immunocytokines, indicating that BP-based nanocomposites not only serve as effective PTAs to ablate large solid tumors but also function as an immunomodulation agent to eliminate discrete tumorlets. Therefore, BP-mediated immunotherapy would provide more possibilities for synergistic cancer treatment.

14.
Mol Ther Oncolytics ; 22: 468-482, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34553033

RESUMO

lncRNA DSCR8 (Down syndrome critical region 8) is involved in progression of many cancers, but its specific role in gastric cancer (GC) is still unclear. Here, qRT-PCR detected upregulated expression of DSCR8 and Cdc42 and downregulated expression of miR-137 in GC. The protein expression level of Cdc42 in GC was upregulated as tested by western blot. Statistical analysis showed that DSCR8 was closely associated with some malignant clinicopathological features (such as tumor size, metastasis, and stage) in GC patients. Fluorescence in situ hybridization showed that DSCR8 was localized in the nucleus and cytoplasm. Dual-luciferase reporter gene, RNA immunoprecipitation, and biotin pull-down assays showed that DSCR8 could bind to miR-137 could bind to Cdc42. In vitro and in vivo assays showed that DSCR8 could promote proliferation, invasion, and the cycle of GC cells and inhibit cell apoptosis. In addition, a rescue experiment showed that DSCR8 regulated progression of GC cells via miR-137. Furthermore, DSCR8 regulated Cdc42 in GC cells by inhibiting miR-137. Taken together, these data indicated that DSCR8 could adsorb miR-137 to reduce its inhibitory effect on Cdc42 expression, thereby promoting the progression of GC cells and regulating the cell cycle. These results provide a novel direction for DSCR8 as a target of GC.

15.
Int J Nanomedicine ; 16: 5811-5829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471353

RESUMO

Advanced research has revealed the crucial role of tumor microenvironment (TME) in tumorigenesis. TME consists of a complicated network with a variety of cell types including endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs) as well as the extracellular matrix (ECM). The TME-constituting cells interact with the cancerous cells through plenty of signaling mechanisms and pathways in a dynamical way, participating in tumor initiation, progression, metastasis, and response to therapies. Hence, TME is becoming an attractive therapeutic target in cancer treatment, exhibiting potential research interest and clinical benefits. Presently, the novel nanotechnology applied in TME regulation has made huge progress. The nanoparticles (NPs) can be designed as demand to precisely target TME components and to inhibit tumor progression through TME modulation. Moreover, nanotechnology-mediated drug delivery possesses many advantages including prolonged circulation time, enhanced bioavailability and decreased toxicity over traditional therapeutic modality. In this review, update information on TME remodeling through NPs-based targeted drug delivery strategies for anticancer therapy is summarized.


Assuntos
Nanopartículas , Neoplasias , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Células Endoteliais , Humanos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
16.
J Mater Chem B ; 9(3): 612-633, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33306079

RESUMO

rHDL is a synthesized drug delivery nanoplatform exhibiting excellent biocompatibility, which possesses most of the advantages of HDL. rHDL shows almost no toxicity and can be degraded to non-toxic substances in vivo. The severe limitation of the application of various antitumor agents is mainly due to their low bioavailability, high toxicity, poor stability, etc. Favorably, antitumor drug-loaded rHDL nanoparticles (NPs), which are known as an important drug delivery system (DDS), help to change the situation a lot. This DDS shows an outstanding active-targeting ability towards tumor cells and improves the therapeutic effect during antitumor treatment while overcoming the shortcomings mentioned above. In the following text, we will mainly focus on the various applications of rHDL in tumor targeted therapy by describing the properties, preparation, receptor active-targeting ability and antitumor effects of antineoplastic drug-loaded rHDL NPs.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Lipoproteínas HDL/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/patologia
17.
Open Life Sci ; 14: 119-125, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33817143

RESUMO

OBJECTIVE: To investigate the HER2/c-erbB-2, epidermal growth factor receptor (EGFR) protein expression in gastric cancer and association with patients' clinical pathology characteristics and prognosis. METHODS: HER2/c-erbB-2 and EGFR protein expression was examined by immunohistochemical assay in gastric cancer tissue and corresponding paired normal gastric tissue of 67 patients of gastric carcinoma. The HER2/c-erbB-2, EGFR protein positive expression rate in cancer tissue and normal gastric tissue were compared. The correlation between HER2/c-erbB-2, EGFR protein positive expression and patients' clinical pathology characteristics and survival was evaluated. RESULTS: The positive expression rate of HER2/c-erbB-2 in the cancer and paired normal gastric tissues were 32.8% (22/67) and 4.5% (3/67), respectively with statistical difference (p<0.05). And the positive expression rate of EGFR in cancer and paired normal gastric tissues were 41.8% (28/67) and 5.9 (4/67), respectively, with statistical difference (p<0.05). HER2/c-erbB-2 positive expression in cancer tissue was significant correlated with the pathology grading (p<0.05), tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05); EGFR positive expression in cancer tissue was significant correlated with the tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05). The median survival time was 13.14 and 23.6 months respectively for HER2/c-erbB-2 positive and negative expression groups respectively with statistical difference ( HR=2.26, 9%CI:1.06-4.80, p<0.05). However, the median survival time was 15.47 and 22.87 months for EGFR positive and negative expression groups respectively, without statistical difference (HR=1.78, 9%CI:0.96-3.29, p>0.05). CONCLUSION: Positive expression of HER2/c-erbB-2 and EGFR proteins in cancer tissue was significant higher than normal gastric tissue and have significant correlation with prognosis.

18.
J Biomed Res ; 29(2): 112-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25859265

RESUMO

Roux-en-Y gastric bypass surgery (RYGB) has been demonstrated to be successful for treating type-II diabetes mellitus (T2DM) patients with a body mass index (BMI) <30 kg/m(2), but reports of RYGB for T2DM patients with a BMI <28 kg/m(2) are lacking. T2DM patients with a BMI <28 kg/m(2) were prospectively recruited to participate in this study in four hospitals. The endpoint was T2DM remission (defined by fasting blood glucose (FBG) level <110 mg/dL and hemoglobin (Hb)A1c level <6.0% at 12 months postoperatively). Predictors of remission were investigated by univariate and multivariate analyses. Eighty-six patients were assessed. Eighty-five patients underwent RYGB, with one conversion to open surgery. We compared the values of various variables before and after surgery. The mean BMI decreased from 24.68±2.12 to 21.72±2.43 kg/m(2) (P<0.001). Fifty-eight (67.4%) patients were not treated by drugs or insulin after surgery, and 20 patients (23.3%) had complete remission of T2DM at 12 months after surgery with an acceptable number of complications. The mean HbA1c level in the remission group was significantly lower than that in the non-remission group. Patients with a higher weight, lower HbA1c level, higher C-peptide level, and higher FBG level were more likely to have T2DM remission in multivariate analyses. In conclusion, RYGB was effective and safe for treating T2DM patients with a BMI <28 kg/m(2). Complete remission can be predicted by cases having a higher weight, lower HbA1c level, higher C-peptide level, and higher FBG level.

19.
Huan Jing Ke Xue ; 32(4): 1042-7, 2011 Apr.
Artigo em Zh | MEDLINE | ID: mdl-21717745

RESUMO

The carbon source in municipal wastewater was adsorbed by activated sludge and then harvested through the hydrolysis of activated sludge. Results indicated that activated sludge had high absorbing ability towards organic carbon and phosphorus under continuous operation mode, and the average COD and TP absorption rate reached as high as 63% and 76%, respectively. Moreover, about 50% of the soluble carbon source was outside of the sludge cell and could be released under mild hydrolysis condition. Whereas the absorbed amount of nitrogen was relatively low, and the removal rate of ammonia was only 13% . Furthermore, the releases of organic carbon, nitrogen and phosphorus from the sludge absorbing pollutants in the wastewater were studied. By comparing different hydrolysis conditions of normal (pH 7.5, 20 degrees C), heating (pH 7.5, 60 degrees C) and the alkaline heating (pH 11, 60 degrees C), the last one presented the optimum hydrolysis efficiency. Under which, the release rate of COD could reach 320 mg/g after 24 hours, whereas nitrogen and phosphorus just obtained low release rates of 18 mg/g and 2 mg/g, respectively. Results indicate that the carbon source in wastewater could be harvested by the adsorption and desorption of activated sludge, and the concentrations of nitrogen and phosphorus are low and would not influence the reuse of the harvested carbon source.


Assuntos
Bactérias/metabolismo , Carbono/metabolismo , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Adsorção , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Cidades , Esgotos/química
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