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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1957-1961, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283726

RESUMO

OBJECTIVE: To investigate the expression of immunoglobulin G (IgG) and its subclasses in patients with multiple myeloma (MM) and lymphoma (LYM) and its correlation with blood cell parameters. METHODS: 129 patients with multiple myeloma and 113 patients with lymphoma diagnosed treated in Sichuan people's Hospital from January to December 2019 were selected and the total IgG and subclass IgG1, IgG2, IgG3 and IgG4, and some parameters of peripheral blood routine in patients were retrospective analyzed. Independent sample t test or nonparametric Mann Whitney U test were used for comparison between the groups. The relationship between IgG subclass and blood cell parameters was analyzed by correlation analysis. For the bivariate normal distribution data, Pearson correlation coefficient was calculated. For bivariate non normal distribution data, the Spearman correlation coefficient was calculated. RESULTS: IgG1 and IgG2 were significantly higher in patients with multiple myeloma than in patients with lymphoma (P=0.001, 0.000, respectively), but IgG3 and IgG4 were significantly lower than in patients with lymphoma (P=0.000, 0.000, respectively), and there was no significant difference for total serum IgG between the two groups (P=0.717). The results showed that the IgG4 content of male patients with multiple myeloma and lymphoma was significantly higher than that of female patients (Z=-3.191, P=0.001); the age, M%, E% of the MM patients were significantly higher than those of the patients with lymphoma (P=0.000, 0.005, 0.019), but WBC, RBC, Hb were significantly lower than those of the patients with lymphoma (P=0.013, 0.000, respectively). The results of Spearman correlation analysis showed that RBC and Hb were decreased with the increasing of IgG and IgG1 in the MM patients(r=0.254, -0.272, -0.248 and -0.289, P=0.004, 0.002, 0.005 and 0.001). With the increasing of IgG4 in the serum of patients with lymphoma, RBC and Hb showed the trendy of decreased (r=-0.240 and, -0.251, respectively, P=0.010, 0.007). CONCLUSION: The detection of IgG subclass and the correlation between IgG subclass and blood cell parameters are great value in the diagnosis and pathogenesis of multiple myeloma and lymphoma.

2.
Cell Death Discov ; 6(1): 133, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33298889

RESUMO

In mammalian early embryos, the transition from maternal to embryonic control of gene expression requires timely degradation of a subset of maternal mRNAs (MRD). Recently, zygotic genome activation (ZGA)-dependent MRD has been characterized in mouse 2-cell embryo. However, in early embryos, the dynamics of MRD is still poorly understood, and the maternal factor-mediated MRD before and along with ZGA has not been investigated. Argonaute 2 (Ago2) is highly expressed in mouse oocyte and early embryos. In this study, we showed that Ago2-dependent degradation involving RNA interference (RNAi) and RNA activation (RNAa) pathways contributes to the decay of over half of the maternal mRNAs in mouse early embryos. We demonstrated that AGO2 guided by endogenous small interfering RNAs (endosiRNAs), generated from double-stranded RNAs (dsRNAs) formed by maternal mRNAs with their complementary long noncoding RNAs (CMR-lncRNAs), could target maternal mRNAs and cooperate with P-bodies to promote MRD. In addition, we also showed that AGO2 may interact with small activating RNAs (saRNAs) to activate Yap1 and Tead4, triggering ZGA-dependent MRD. Thus, Ago2-dependent degradation is required for timely elimination of subgroups of maternal mRNAs and facilitates the transition between developmental states.

3.
BMC Cancer ; 20(1): 1139, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228579

RESUMO

BACKGROUND: The recommended cumulative doxorubicin dose in soft tissue sarcoma (STS) treatment was based on cardiotoxicity data from retrospective studies of breast cancer patients. However, the treatment and prognosis of STS and breast cancer are quite different, and reference to breast cancer data alone may not reflect the efficacy of doxorubicin treatment in STS. This study, thus, aimed to review and analyze clinical data of STS patients treated with a high cumulative doxorubicin dose, to provide a reference for treatment selection and clinical trial design. METHODS: We retrospectively collected and analyzed clinical data of patients with advanced STS who received doxorubicin-based chemotherapy from January 2016 to January 2020. The patients were divided into a standard-dose group (who received ≤6 cycles of doxorubicin after the initial diagnosis) and an over-dose group (who were re-administered doxorubicin [doxorubicin-rechallenge] after receiving 6 cycles of doxorubicin therapy discontinuously). Patient characteristics, cumulative doxorubicin dose, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), cardiotoxicity incidence, and treatment effectiveness were evaluated in both groups. RESULTS: A total of 170 patients with advanced STS were recruited (146 in the standard-dose group and 24 in the over-dose group). The average cumulative doxorubicin dose was 364.04 ± 63.81 mg/m2 in the standard-dose group and 714.38 ± 210.09 mg/m2 in the over-dose group. The ORR, DCR, and median PFS were 15.07, 58.9%, and 6 (95% confidence interval [CI]: 5.8-6.5) months in the standard-dose group and 16.67, 66.67%, and 4 (95%CI: 2.0-5.8) months in the over-dose group, respectively. Symptomatic heart failure occurred in five patients (3.42%) of the standard-dose group and in one patient (4.17%) of the over-dose group. In these patients with cardiotoxicity, doxorubicin was discontinued, and all of them died of uncontrolled tumor growth. No drug-related deaths occurred. CONCLUSIONS: The continuation of or rechallenge with doxorubicin beyond the recommended cumulative dose could be a promising therapeutic option in the treatment of chemotherapy-sensitive advanced sarcomas. Further evaluation is necessary in prospective trials.

4.
Adv Mater ; : e2006752, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175432

RESUMO

Afterglow imaging that detects photons after cessation of optical excitation avoids tissue autofluorescence and thus possesses higher sensitivity than traditional fluorescence imaging. Purely organic molecules with room-temperature phosphorescence (RTP) have emerged as a new library of benign afterglow agents. However, most RTP luminogens only emit visible light with shallow tissue penetration, constraining their in vivo applications. This study presents an organic RTP nanoprobe (mTPA-N) with emission in the NIR range for in vivo afterglow imaging. Such a probe is composed of RTP molecule (mTPA) as the phosphorescent generator and an NIR-fluorescent dye as the energy acceptor to enable room-temperature phosphorescence resonance energy transfer (RT-PRET), ultimately resulting in redshifted phosphorescent emission at 780 nm. Because of the elimination of background noise and redshifted afterglow luminescence in a biologically transparent window, mTPA-N permits imaging of lymph nodes in living mice with a high signal-to-noise ratio. This study thus opens up a universal approach to develop organic RTP luminogens into NIR afterglow imaging agents via construction of RT-PRET.

5.
Anticancer Drugs ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33105152

RESUMO

This study was performed to investigate pneumothorax characteristics and association with clinical outcomes in patients with osteosarcoma treated with apatinib. We retrospectively reviewed the medical records of osteosarcoma patients treated with apatinib between January 2016 and April 2020 at three institutions. We evaluated the prevalence, healing time, recurrence, severity, clinical management, and prognosis of pneumothorax in these patients. A total of 54 osteosarcoma patients who received apatinib treatment were enrolled in this study. Among them, 14 patients had pneumothorax. There were significant differences between the patients with and without pneumothorax with regard to the cavitating rate of lung metastases (92.86 vs. 32.50%, respectively, P < 0.001), objective response rate (42.86 vs. 10.00%, P = 0.013), disease control rate (85.71 vs. 42.50%, P = 0.006), 4-month progression-free survival (PFS) rate (57.10 vs. 20.00%, P < 0.001), and median PFS (5.65 vs. 2.90 months, P = 0.011). Compared with pneumothorax patients treated with chest tube drainage only [non-staphylococcal enterotoxin C (SEC) group], those treated with chest tube drainage and SEC thoracic perfusion in parallel (SEC group) had a shorter pneumothorax healing time (12.00 ± 4.50 days vs. 24.00 ± 14.63 days for SEC group and non-SEC group, respectively, P = 0.103), a lower recurrence rate of pneumothorax (25.00% vs. 66.67%, P = 0.277), and a longer median PFS (5.9 months vs. 4.75 months, P = 0.964). however, these numerical differences for the SEC/non-SEC data did not reach statistical significance. Pneumothorax and cavitation in lung metastases may be effective prognostic markers for patients with osteosarcoma treated with apatinib. SEC may be effective for treatment of such pneumothorax patients, warranting further study.

6.
BMC Cancer ; 20(1): 698, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723378

RESUMO

BACKGROUND: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the evidence and clinical data of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare. METHODS: The clinical data of metastatic STS patients who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively analysed. All these patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the effectiveness and safety of nab-paclitaxel and gemcitabine in these patients. RESULTS: A total of 17 patients treated with nab-paclitaxel/ gemcitabine were enrolled in this study. One patient with angiosarcoma achieved complete response, 6 patients had partial response, 5 patients achieved stable disease, and 5 patients had progressive disease. The average diameter change in target lesion from baseline was - 19.06 ± 45.74%. And median progression free survival was 6 months (95% CI, 2-9 months). Grade 3 / 4 adverse events were not common, included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. CONCLUSION: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

7.
Virol J ; 17(1): 100, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650791

RESUMO

BACKGROUND: HPV persistent infection is a strong carcinogenic factor that can induce cervical cancer. Investigation of HPV epidemiology and genotype distribution is of great meaning for the development of cervical cancer prevention and control strategies. METHODS: By using PCR-based hybridization gene chip assay, HPV genotype was detected from 14,185 women that came from HEC (Health Examination Center) or OGOC (Obstetrics and Gynecology Outpatient Clinics) between 2015 and 2017 in Sichuan area. The epidemiology and genotype distribution as well as the relationship between HPV infection and histology/cytology abnormalities were analyzed. RESULTS: The positivity rate of HPV was 23.84%. The HPV-positive rate of OGOC group (37.62%) was significantly higher than that of HEC group (15.29%), p < 0.05. The prevalence of HPV reached peak at age 41-50 (5.86%) in HEC group, but at age 21-30 (14.74%) in OGOC group. Of all the HPV positive women, single genotype infection was the most common form in both HEC and OGOC group (62.06% in total screening population, 74.36% in HEC group and 54.01% in OGOC group). Three most prevalent HPV types were HPV-52 (5.02%), 58 (3.61%), and 16 (3.24%) in total screening population. Of all the HPV positive women, the top three types were HPV-52 (20.93%), CP8304 (15.32%), and 58 (14.42%) in HEC group, while were HPV-52 (21.14%), 16 (16.34%), and 58 (15.61%) in OGOC group. HPV 52/16/58 accounted for 41.84% of cytology and 56.52% of histological abnormalities. CONCLUSIONS: Women in Sichuan area were facing the great threat of HPV infection, especially the women aged between 21 ~ 30 or 41-50 years old. The priority HPV types were HPV 52, 58, and 16 in OGOC group, while were HPV 52, CP8304, and 58 in HEC group. HPV 52/16/58 accounted for the majority of cytology and histological abnormalities. Our analysis was found to be valuable for providing a scientific basis for the prevention and control strategies of cervical cancer in Sichuan area.

8.
Medicine (Baltimore) ; 99(27): e20715, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629645

RESUMO

To understand the feasibility, clinical effect, and complications related to biological reconstruction techniques for long limb malignant bone tumors after excision.This retrospective study included eighty patients with malignant bone tumors treated at our hospital between January 2007 and January 2019. After tumor resection, 52 cases of intercalary and 28 cases of osteoarticular bone grafts were used. The implanted bone included devitalized recycling bone, fibular, and allograft.The average follow up period was 42.19 months for 80 patients, among whom 15 (18.75%) died. The 5-year EFS and OS were 58% and 69%, respectively. The average length of the replanted bone was 18.57 cm. The MSTS scores of intercalary and osteoarticular bone grafts were 87.24% and 64.00%, respectively. In 23 cases (44.23%) of metaphyseal and 26 cases (32.5%) of the diaphysis, bone graft union was obtained at the first stage. The factors affecting bone union were the patient's gender, age, devitalization bone methods and whether the implanted bone was completely fixed. Postoperative complications included delayed bone union in 15 patients, fractures in 25 cases, nonunion in 22 cases, bone resorption in 14 cases, and postoperative infection in 4 cases. Twenty-eight cases of bone grafting required revision surgery, including replacement of internal fixation, autologous bone graft, debridement, removal of internal fixation, and replacement with prosthetic replacement.Biological reconstructions with massive bone grafts are useful in the reconstruction of certain malignant extremity bone tumors after wide excision.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Neoplasias Femorais/cirurgia , Úmero/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Sarcoma/cirurgia , Tíbia/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
9.
Angew Chem Int Ed Engl ; 59(45): 20161-20166, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32710517

RESUMO

Herein, norbornyl (NB), a bulky annular nonconjugated spacer, is melded into π systems to construct two groups of ladder-type room-temperature phosphorescence (RTP) luminogens. The effect of the NB on π-π interactions, packing modes and RTP performance is explored systematically. The experimental and computational results demonstrate the versatility of NB in reducing π-π distances and synergistically intensifying the intermolecular interactions, which not only induces intersystem crossing from S1 to Tn but also diminishes the nonradiative decay of triplet excitons. Impressively, 1800-fold phosphorescence lifetime enhancement is achieved in comparison with the reference compounds without NB. The molecular packing and RTP performance can be further modulated by the length of the backbones and terminal end-groups. It is quite peculiar that NB-annulated phthalic acid exhibits reversible photochromism in the solid state, likely due to the formation of persistent radical pairs. Our study paves an ingenious avenue towards enhancing intermolecular interactions and provides significant implications for a better comprehensive understanding of the origin of their RTP and the inherent photophysical mechanism.

10.
Cell Stem Cell ; 27(2): 315-325.e5, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32559418

RESUMO

Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significant epigenetic barriers. Genomic imprinting is not generally regarded as such a barrier, although H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblast and extraembryonic tissues. Here we report significant enhancement of SCNT efficiency by deriving somatic donor cells carrying simultaneous monoallelic deletion of four H3K27me3-imprinted genes from haploid mouse embryonic stem cells. Quadruple monoallelic deletion of Sfmbt2, Jade1, Gab1, and Smoc1 normalized H3K27me3-imprinted expression patterns and increased fibroblast cloning efficiency to 14% compared with a 0% birth rate from wild-type fibroblasts while preventing the placental and body overgrowth defects frequently observed in cloned animals. Sfmbt2 deletion was the most effective of the four individual gene deletions in improving SCNT. These results show that lack of H3K27me3 imprinting in somatic cells is an epigenetic barrier that impedes post-implantation development of SCNT embryos and can be overcome by monoallelic imprinting gene deletions in donor cells.

11.
Food Sci Nutr ; 8(4): 1914-1922, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32328257

RESUMO

Delivery systems for controlled release of fragrances are significantly essential in the flavor and fragrance industry due to a limited life span (premature evaporation and degradation) of fragrance compounds. Recently, several adsorption materials such as porous materials have been developed in delivery systems for targeted fragrance release. In this work, UiO-66, a member of metal-organic framework (MOF) family with high porosity and greater adsorbability, was selected as a prospective alternative to traditional porous adsorbents for controlled release of fragrances. Isophorone, eugenol, and ß-ionone with strong aroma are widely used as perfume flavors, soap flavor, cosmetic flavors, and even as a food-flavoring agents, and were chosen as representative fragrances for adsorption and controlled release studies. The adsorption and release behavior of fragrances on UiO-66 was evaluated by high-performance liquid chromatography (HPLC). The UiO-66 with high surface area (1,076 m2/g) achieved effective storage and controlled release for isophorone, eugenol, and ß-ionone. The adsorption rates of isophorone, eugenol, and ß-ionone can reach 99.4%, 99.9%, and 60.2%, respectively. Additionally, the release of these fragrances from UiO-66 can sustain over 20 days. UiO-66 exhibited higher release rate over eugenol with desorption rates of 95.2% than that of ß-ionone (52.6%) and isophorone (49.6%), respectively, suggesting a good adsorption-release selectivity of UiO-66 to different fragrances. This study further confirms the usability of UiO-66 in fragrance release and extends the application of MOF porosity in aroma release.

12.
Ann Transl Med ; 8(5): 239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309386

RESUMO

Background: Maternal embryonic leucine zipper kinase (MELK) is an atypical member of the snf1/AMPK family of serine-threonine kinases, involved in diverse physiological and pathological processes, including cell proliferation, apoptosis, embryogenesis, cancer treatment resistance, and RNA processing. MELK is highly expressed in human cancers and is associated with more aggressive forms of astrocytoma, glioblastoma, breast cancer, and melanoma to date, no information about porcine MELK (pMELK) has been reported. Methods: In this study, the pMELK coding sequence was cloned from swine spleen and characterized. We also quantitatively determined the expression of MELK in 11 tissues isolated from a piglet and determined its subcellular localization when expressed in swine umbilical vein endothelial cells (SUVEC) as a fusion protein. Moreover, we report the functional characterization of pMELK protein concerning its role in apoptosis. Results: Sequencing analysis showed that full-length of pMELK is 2,072 bp with 17 exons, encoding 655 amino acids, including an S-TKc conserved domain. Comparison of pMELK with ten other mammalian species of their orthologous sequences showed >91% homology and an evolutionary distance <0.05, demonstrating that MELK is highly conserved in evolution. Relative quantification of MELK expression in 11 tissue samples isolated from 30-day-old piglets showed MELK expression in all tested organs and the highest expression in the superficial inguinal lymph node. Constructed a plasmid named pEGFP-MELK, and the fusion protein GFP-MELK was successfully expressed in SUVECs. Fluorescence microscopy revealed the subcellular distribution of the fusion protein GFP-MELK was limited to the cytoplasm. About function, Flow cytometry analysis showed that overexpression of GFP-pMELK in SUVEC cells enhances staurosporine (STS)-induced apoptosis, but not significantly different. The pMELK protein also was found to interact with porcine BCL-G and transient transfection of the recombinant plasmid pCMV-HA-pMELK into SUVEC cells stably expressing GFP-pBCL-G protein inhibited pBCL-G -induced apoptosis significantly. Conclusions: The present study provided useful information on pMELK basic details and function in apoptosis offer a potential new molecular model for disease interventions and disease related to human MELK and BCL-G.

13.
Cancer Manag Res ; 12: 1339-1346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158266

RESUMO

Purpose: Programmed cell death 1 (PD-1) inhibitors are ineffective as monotherapy for the treatment of soft tissue sarcomas (STS). However, increasing evidence shows that the combination of PD-1 inhibitors and chemotherapy is efficacious and safe for many types of malignancies, including STS. This study aimed to assess the safety and efficacy of doxorubicin chemotherapy plus PD-1 inhibitor in the treatment of metastatic STS. Patients and Methods: We retrospectively reviewed 21 patients with metastatic STS who received doxorubicin chemotherapy plus a PD-1 inhibitor between November 2017 and October 2018. Results: The objective response rate was 47.6%, the disease control rate was 71.40%, and the median progression-free survival was 6 months (95% CI, 2-8 months). The average change in target lesion diameter from baseline was -25.15 ± 41.61. Majority of the patients experienced grade 1/2 adverse events (AEs), the grade 3/4 AEs were few. The most common grade 3/4 AEs were as follows: leukopenia (23.8%) and anemia (19.0%). Immune-related AEs were common and included hypothyroidism (14.3%) and pneumonitiss (9.5%). No drug related deaths occurred. Conclusion: This study provides preliminary evidence that the combination of doxorubicin chemotherapy and PD-1 inhibitor for advanced STS is safe and effective. We plan to conduct randomized clinical trials to confirm and characterize the activity of the chemotherapy-immunotherapy combinations in the treatment of sarcomas.

14.
Proc Natl Acad Sci U S A ; 117(8): 4328-4336, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32029582

RESUMO

Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism. Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction, leading to key accelerated aging phenotypes. Restoration of mitochondrial activity can rescue age-related macular degeneration (AMD) phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial (RPE) cells. We revealed an epigenetic-metabolism axis contributing to aging and potentially to antiaging therapy.

15.
Invest New Drugs ; 38(5): 1559-1569, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32100146

RESUMO

Background Previous studies have demonstrated the efficacy of apatinib and anlotinib for the treatment of sarcomas. However, more clinical data and evidence are needed to support clinical treatment selection and study design. Here, we evaluated the effectiveness and safety of these two drugs for the treatment of sarcomas. Methods We retrospectively reviewed the data of 110 patients with advanced osteosarcoma (n = 32) or soft tissue sarcoma (STS, n = 78) who received oral apatinib or anlotinib therapy during May 2016-February 2019 at two centers. Patients were divided into the apatinib and anlotinib groups. Results Among osteosarcoma patients, the objective response rates (ORRs) for the apatinib and anlotinib groups were 15.79% (3/19) and 7.69% (1/13), respectively. The disease control rates (DCRs) were 63.16% (12/19) and 30.77% (4/13), and the median progression-free survival (m-PFS) was 4.67 ± 3.01 and 2.67 ± 1.60 months, respectively. Among STS patients, ORRs for the apatinib and anlotinib groups were 12.24% (6/49) and 13.79% (4/29), respectively. The DCRs were 59.18% (29/49) and 55.17% (16/29), and m-PFS was 7.82 ± 6.90 and 6.03 ± 4.50 months, respectively. Regarding adverse events (AEs), apatinib was associated with a higher incidence of hair hypopigmentation and pneumothorax, while anlotinib was associated with a higher incidence of pharyngalgia or hoarseness. Conclusion Both apatinib and anlotinib were effective for the treatment of sarcomas. However, the effectiveness of the two drugs and associated AEs varied based on the histological type of sarcoma. These differences may be due to their different sensitivities to targets such as RET, warranting further study.

16.
Onco Targets Ther ; 13: 1561-1568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110053

RESUMO

Purpose: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. Patients and Methods: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. Results: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. Conclusion: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.

17.
Angew Chem Int Ed Engl ; 59(25): 9946-9951, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31944514

RESUMO

Room-temperature phosphorescence (RTP) emitters with ultralong lifetimes are emerging as attractive targets because of their potential applications in bioimaging, security, and other areas. But their development is limited by ambiguous mechanisms and poor understanding of the correlation of the molecular structure and RTP properties. Herein, different substituents on the 9,9-dimethylxanthene core (XCO) result in compounds with RTP lifetimes ranging from 52 to 601 ms, which are tunable by intermolecular interactions and molecular configurations. XCO-PiCl shows the most persistent RTP because of its reduced steric bulk and multiple sites of the 1-chloro-2-methylpropan-2-yl (PiCl) moiety for forming intermolecular interactions in the aggregated state. The substituent effects reported provide an efficient molecular design of organic RTP materials and establishes relationships among molecular structures, intermolecular interactions, and RTP properties.

18.
World J Surg Oncol ; 18(1): 23, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996228

RESUMO

BACKGROUND: The proximal humerus is one of the most common sites of primary or metastatic malignant tumors. Reconstruction of the shoulder after tumor resection is controversial and challenging. When intra-articular resection is performed, biological reconstruction (osteoarticular allograft and autologous bone implantation) may be the first choice rather than prosthetic reconstruction. OBJECTIVE: To observe the mid- to long-term effects of oncologic, reconstructive, and functional outcomes of two different biological reconstruction methods for resection of humerus osteosarcoma involving caput humeri. METHODS: This was a retrospective study of 13 consecutive patients who underwent humeral reconstruction of osteosarcoma including caput humeri using osteoarticular allograft (n = 7) and tumor bone inactivated and reimplantation (TBIR, n = 6) in our clinic between 2007 and 2017. Patients' general information, resection and reconstruction techniques, oncological and functional outcomes, and complications were collected and evaluated. Different complications of implantations were compared and analyzed for the different biological methods. RESULTS: The study included ten males and three females with an average age of 19.15 years. The operation time was about 3.65 h with an average blood loss of 631 ml. The resection tumor bones were 13-45 cm (23.54 cm on average). The mean follow-up period was 5.27 years. The shoulder movement was 10-70° (average, 44.00°) in abduction, 0-30° (average, 14.17°) in flexion, and 0-20° (average, 11.90°) in extention at the last follow-up. The complications included fracture in four TBIR patients and two allograft patients with an average of 2.67 years postoperation. Fracture rate was higher and appeared time was earlier in TBIR patients than in allograft patients (p = 0.04); caput humeri absorption occurred in all seven allograft patients and three TBIR patients at an average of 3.10 years after surgery; severe graft bone resorption appeared in five TBIR patients and two allograft patients at an average of 2.57 years of follow-up. CONCLUSIONS: Humerus biological reconstruction involving caput humeri was associated with a high complication rate and acceptable limb function in the mid to long term. New combined biological methods should be explored and adopted in the future.


Assuntos
Neoplasias Ósseas/cirurgia , Úmero/cirurgia , Osteossarcoma/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Ombro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Úmero/patologia , Masculino , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Ombro/patologia , Adulto Jovem
19.
Cell Prolif ; 53(1): e12724, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794640

RESUMO

OBJECTIVE: In this study, we generated an Rbm14 knockout mouse model to explore its functions during early mouse embryogenesis. MATERIALS AND METHODS: The Rbm14 knockout mouse model was generated by a combination of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and microinjection techniques. The developmental defects of the knockout embryos were characterized by histological analyses. The accumulation of DNA damage in mouse embryonic stem cells (ESCs) was detected by γH2AX staining and comet assay. The altered mRNA splicing of DNA damage response (DDR)-related genes was detected by RNA-Seq analysis and confirmed by semi-quantitative PCR. The interaction of RBM14 with alternative splicing-related genes was detected by immunoprecipitation-mass spectra (IP-MS) and confirmed by co-immunoprecipitation (Co-IP). RESULTS: Rbm14 knockout in mice results in apoptosis and cell proliferation defects in early post-implantation epiblast cells, leading to gastrulation disruption and embryonic lethality. FACS and immunostaining demonstrate accumulation of DNA damage in Rbm14 knockout ES cells. We also identified altered splicing of DDR-related genes in the knockout mouse ESCs by RNA-Seq, indicating that RBM14-mediated alternative splicing is required for the maintenance of genome integrity during early mouse embryogenesis. CONCLUSIONS: Our work reveals that Rbm14 plays an essential role in the maintenance of genome integrity during early mouse embryonic development by regulating alternative splicing of DDR-related genes.


Assuntos
Processamento Alternativo , Apoptose , Desenvolvimento Embrionário , Instabilidade Genômica , Células-Tronco Embrionárias Murinas/metabolismo , Fatores de Transcrição/metabolismo , Animais , Dano ao DNA , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Fatores de Transcrição/genética
20.
Sci Rep ; 9(1): 19619, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873114

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide, with 50-70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.


Assuntos
Neoplasias Ósseas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Proteínas com Motivo Tripartido/biossíntese , Células A549 , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Proteínas com Motivo Tripartido/genética
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