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2.
Clin Case Rep ; 11(8): e7780, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37609641

ABSTRACT

ECD is considered to have rapid progression and poor prognosis. Studies have shown that vemurafenib is effective for ECD patients with orbital involvement, but not for ECD with multiple organs. The refinement of treatment approaches and the increased awareness of ECD have led to a dramatic improvement in prognosis.

3.
Bull Cancer ; 110(3): 285-292, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36739242

ABSTRACT

The traditional immunotherapy is limited on relapsed/refractory metastatic ovarian cancer because tumors cause immunosuppression. Since new therapeutic strategies to improve clinical outcomes for patients with relapsed/refractory metastatic ovarian carcinoma are needed, the aim of this study was to evaluate the therapeutic effect of haploidentical peripheral blood stem cells (haplo-PBSCs) adoptive treatment on relapsed/refractory ovarian cancer. Thirteen patients with advanced stage of ovarian cancer and refractory history after surgery and chemotherapy were treated with interleukin-2 activated haplo-PBSCs donated by their parents or children. Clinical outcomes including therapeutic response by measuring tumor size changes using CT scanning, CA-125 levels and survival times were evaluated. T and NK cell population in patients before and after treatment was detected by flow cytometry analysis. The median follow-up time after haplo-PBSCs adoptive treatment was 14 months. At the time of the last follow-up, the median overall survival after haplo-PBSCs adoptive treatment was 9.1 months. Ten patients (76.9%) achieved a relief of symptoms, including abdominal distention, ache, fatigue, and poor appetite. During the first 2 months after treatment, CA125 levels decreased in 10 patients (76.9%). Five patients (38.5%) had a stable disease and 1 patient (8%) had partial response. T cell population (CD3+CD4+ and CD3+CD8+) and CD3-CD16+CD56+ NK cells were increased in patients after haplo-PBSCs adoptive treatment. Our study reveals that haplo-PBSCs adoptive treatment is associated with an anti-tumor effect and increasing immune responses in patients with relapsed/refractory ovarian cancer.


Subject(s)
Hematopoietic Stem Cell Transplantation , Ovarian Neoplasms , Peripheral Blood Stem Cells , Child , Humans , Female , Treatment Outcome , Neoplasm Recurrence, Local
4.
Clin Lung Cancer ; 23(8): 709-719, 2022 12.
Article in English | MEDLINE | ID: mdl-35995696

ABSTRACT

INTRODUCTION: Can the Cytokine-induced killer (CIK) cells in combination with immune checkpoint inhibitor further improve the efficacy of chemotherapy in non-small cell lung cancer (NSCLC) patients? What are the adverse reactions of this combination therapy? But these problems are not clear. Therefore, we conducted a phase 1b trial to evaluate the safety and efficacy of autologous CIK cells therapy combined with Sintilimab, antibody against programmed cell death-1, plus chemotherapy in untreated, advanced NSCLC patients. PATIENTS AND METHODS: Patients with stage IIIB/IIIC/IV NSCLC received Sintilimab, platinum-based doublet chemotherapy, and CIK cells every 3 weeks for 4 cycles, then maintenance treatment with Sintilimab in squamous and with Sintilimab plus pemetrexed in non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years. The primary endpoints were safety and objective response rate (ORR). RESULTS: Thirty-four patients received the treatment. 94.1% of patients experienced treatment-related adverse events (TRAEs). Grade 3 or greater TRAEs occurred in 64.7% of patients. One (2.9%) patient died of grade 5 immune-related pneumonia. The ORR and DCR were 82.4% (95% CI, 65.5%-93.2%) and 100.0% (95% CI, 89.7%-100.0%), respectively. Objective responses were evaluated in 14 of 15 non-squamous patients (93.3%; 95% CI, 68.1%-99.8%) and in 14 of 19 squamous patients (73.7%; 95% CI, 48.8%-90.9%). Median PFS was 19.3 months (95% CI, 8.3 months to not available). CONCLUSION: Autologous CIK cells immunotherapy in combination with Sintilimab plus chemotherapy was well tolerable and showed encouraging efficacy in patients with previously untreated, advanced NSCLC (ClinicalTrials.gov number, NCT03987867).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cytokine-Induced Killer Cells , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Cytokine-Induced Killer Cells/metabolism , Antibodies, Monoclonal , Lung Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis
5.
Clin Case Rep ; 9(7): e04487, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34322251

ABSTRACT

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an extremely poor prognosis making it a therapeutic challenge. However, the development of genetic variation molecular diagnosis and targeted agents has brought the treatment of such malignancies to the precision era. Co-existing mutations of EGFR and MET have been reported in NSCLC, but rarely found in PSC. We herein present a rare case of a 74-year-old female patient diagnosed with PSC, carrying an activating mutation in exon 21 L858R of EGFR and a concurrent MET amplification prior to treatment. Combined application of gefitinib and crizotinib, inhibitors targeting EGFR and MET, respectively, was prescribed. The patient experienced a partial response and was stable for 9.7 months off therapy. The observation stresses the importance of genetic testing and paves the way for combined targeted strategies in PSC.

6.
Front Chem ; 7: 502, 2019.
Article in English | MEDLINE | ID: mdl-31380347

ABSTRACT

A series of ZSM-5 zeolites with hierarchical porous structure were synthesized using NaOH solutions treatment method. The structural and acidity properties of hierarchical ZSM-5 zeolites as-synthesized were characterized by X-ray diffraction (XRD), N2 adsorption, scanning electron microscope (SEM), NH3-temperature programmed desorption (TPD), and pyridine Fourier transform infrared spectroscopy (Py-FTIR). The adsorption and diffusion performances of benzene in hierarchical ZSM-5 zeolites were studied by an intelligent gravimetric analyzer (IGA). It was found that mass transfer (adsorption and diffusion) performance of benzene was significantly affected by synergetic effect of hierarchical structure, acid amount, acidity, adsorption sites of ZSM-5 zeolites. After suitable alkali treatment, the crystal structure of ZSM-5 was retained and finely tailored. Hierarchical ZSM-5 was obtained with a uniform size of mesoporous and microporous structure. Acidity of hierarchical ZSM-5 zeolites was improved, which produced more adsorption sites and thus increased the adsorption performance of benzene in hierarchical ZSM-5. As a result, connectivity in hierarchical ZSM-5 was improved with increasing of mesopores in hierarchical ZSM-5. Hierarchical ZSM-5 well-contributed to the adsorption performance of benzene on active sites and improved catalytic performance of hierarchical ZSM-5.

7.
Pharmaceutics ; 11(1)2019 Jan 04.
Article in English | MEDLINE | ID: mdl-30621141

ABSTRACT

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.

8.
Int J Pharm ; 556: 217-225, 2019 Feb 10.
Article in English | MEDLINE | ID: mdl-30557679

ABSTRACT

Nanocrystals has been constructed for insoluble drugs as a novel type of nanoscale drug delivery systems with high drug loading. How to prepare nanocrystals with good stability and tumor targeting capability is still challenging. This study was to modify paclitaxel nanocrystals with polyethylene glycol (PEG) for stabilization and RGD peptide for tumor targeting. Inspired by the structure of mussel's foot protein, polydopamine (PDA) was introduced to the drug delivery system for the modification of nanocrystals. Briefly, PDA was coated on the surface of nanocrystals to form a reaction platform for further PEGylation and RGD peptide conjugation. PEGylated nanocrystals with RGD peptide modification (NC@PDA-PEG-RGD) were prepared with near-spheroid shape, drug loading 45.12 ±â€¯1.81% and a hydrodynamic diameter 419.9 ±â€¯80.9 nm. The size of NC@PDA-PEG-RGD remained basically unchanged for at least 72 h in the presence of plasma while the size of unmodified nanocrystals (NC) increased and exceeded 1000 nm in 12 h. Cellular uptake and cellular growth inhibition experiments using the lung cancer cell line A549 demonstrated the superiority of NC@PDA-PEG-RGD over NC or PEGylated nanocrystals without RGD modification (NC@PDA-PEG). In A549 model tumor bearing-mice, NC@PDA-PEG-RGD showed significantly higher intratumor accumulation and slower tumor growth than NC@PDA-PEG or free paclitaxel. In summary, our study suggested the superiority of RGDmodified PEGylated paclitaxel nanocrystals as a lung cancer-targeted delivery system and the potential of PDA coating technique for targeting functionalization of nanocrystals.


Subject(s)
Lung Neoplasms/drug therapy , Oligopeptides/chemistry , Paclitaxel/administration & dosage , Polyethylene Glycols/chemistry , A549 Cells , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chemistry, Pharmaceutical/methods , Drug Delivery Systems , Humans , Hydrodynamics , Indoles/chemistry , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles , Oligopeptides/administration & dosage , Paclitaxel/chemistry , Paclitaxel/pharmacology , Particle Size , Polymers/chemistry , Time Factors
9.
J Breast Cancer ; 21(2): 150-157, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29963110

ABSTRACT

PURPOSE: The treatment of triple-negative breast cancer (TNBC) remains challenging, due to the absence of estrogen, progesterone, and human epidermal growth factor receptors. This study was designed to evaluate the efficiency and safety of cytokine-induced killer (CIK) cell immunotherapy, following regular chemotherapy, for patients with TNBC. METHODS: A total of 340 patients with postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this retrospective study. Seventy-seven patients received CIK cell immunotherapy, following regular chemotherapy (arm 1), and 263 patients received regular chemotherapy alone (arm 2). The primary aim was overall survival (OS) and disease-free survival (DFS), and the treatment responses and adverse events were also evaluated. RESULTS: The 5-year DFS and OS rates in arm 1 were 77.9% and 94.3%, compared with 69.8% and 85.6% in arm 2, respectively (p=0.159 and p=0.035, respectively). This clearly shows that there was no statistical difference in the 5-year DFS between the two groups. Multivariate analyses of arm 1 indicated that a Karnofsky performance score (KPS) ≥90 and stage I/IIA disease were significantly associated with a prolonged DFS period (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.09-0.74; p=0.012; and HR 0.21; 95% CI, 0.06-0.82; p=0.024, respectively), but a KPS ≥90 and stage I/IIA disease were not independent prognostic factors for OS. Toxicity was mild in patients who received the CIK therapy. CONCLUSION: The data suggested that CIK cell immunotherapy improved the efficiency of regular chemotherapy in patients with TNBC, and the side effects of CIK cell immunotherapy were mild.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-801681

ABSTRACT

@# Objective: To explore the relationship between monocyte-to-lymphocyte ratio (MLR) in peripheral blood of patients with pulmonary sarcomatoid carcinoma (PSC) and their clinicopathological features and prognosis, and to investigate its clinical significance. Methods: A retrospective analysis was carried out to analyze the complete case data of 80 patients with PSC from October 2010 to April 2017 in Tianjin Cancer Hospital (monocyte and lymphocyte counts of peripheral blood, clinicopathological features, and survival follow-up). The receiver operating curve (ROC) was used to determine the best cut-off value of MLR for the prediction of overall survival time (OS). The patients were divided into high MLR group and low MLR group. Kaplan-Meier method was used to calculate OS and draw survival curves. The Log-Rank test was used to compare the difference in OS between the two groups. The variables with statistical significance in univariate analysis were included into the COX risk regression model to verify and calculate thehazard ratio (HR)and 95% confidence interval (95%CI). Results: The absolute median values of monocytes and lymphocytes were 0.63×109/L and 1.84×109/L, respectively. The best cut-off value of MLR is 0.44. Univariate analysis shows that MLR≥0.44 (P<0.01), no radical surgery (P<0.01), clinical stage Ⅲ+Ⅳ (P<0.01), tumor maximal diameter > 3 cm (P<0.01), and LDH>247 U /L (P<0.01) are the poor prognostic factors affecting overall survival. Multivariate analysis shows that MLR≥0.44(HR=3.554; 95%CI=1.671-6.125; P<0.01), and clinical stage Ⅲ+Ⅳ(HR=3.275; 95%CI=2.047-9.399; P<0.01) are the independent risk factors for the overall survival of PSC, and radical surgery is an independent protective factor affecting the overall survival of PSC(HR=0.360; 95%CI=0.195-0.848; P<0.01). Conclusion: High MLR is an independent risk factor for poor prognosis in patients with PSC.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-821260

ABSTRACT

@#[Abstract] Objective: To explore the relationship between the preoperative blood indicators (platelets, monocytes, neutrophils-to-lymphocyte ratio) and clinicopathological characters and the prognosis of the early stage malignant melanoma(MM)patients. Methods: Clinicopathological data of 120 cases of stage I-III MM patients, who received initial treatment and radical operation in the Cancer Hospital of Tianjin Medical University from January 2007 to May 2012, were obtained for this study. The correlations between parameters of PLR (platelet-to-lymphocyte ratio), LMR (lymphocyte-to-monocyte ratio), NLR (neutrophil-to-lymphocyte ratio), hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets, lactate dehydrogenase, age, stage as well as ulcer and the prognosis of the patients were evaluated. Results: Patients whose tumor with ulceration have higher NLR and basophilic granulocyte (all P< 0.05). Univariate analysis showed that NLR, PLR, LMR, neutrophil, lymphocyte, monocyte, lactic dehydrogenase, age, stage and ulceration were the risk factors of poor 5-year overall survival (P<0.05). The multivariate analysis identified PLR(HR=4.206, 95%CI:1.65410.696, P<0.01),stage(HR=7.670, 95%CI:3.977-14.795, P<0.01)and ulceration(HR=1.931, 95%CI:1.029-3.623, P<0.05)as independent risk factors for the prognosis of the MM patients. Conclusion: Higher preoperative PLR can be used as a predictive factor for poor prognosis of the early stage MM patients.

12.
J Cancer ; 8(16): 3287-3295, 2017.
Article in English | MEDLINE | ID: mdl-29158802

ABSTRACT

Background Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. Objective This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. Methods The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed in vitro. Results After A549/DDP co-culture with CIK cells, the DDP resistance of A549/DDP significantly decreased in a time-dependent manner. The DDP resistance of A549/DDP co-cultured with CIK cells for 20 h decreased 4.93-fold compared with that of A549/DDP cells cultured alone (P<0.05). The mRNA and protein expression levels of the glutathione-S-transferase (GST) -π gene in A549/DDP significantly decreased after co-culture with CIK cells (P<0.05). The secretion of interferon (IFN)- γ significantly increased along with the co-culture time of A549/DDP with CIK cells. The expression of GST-π was restored by adding the neutralizing IFN-γ. Conclusion CIK cells can reverse the drug resistance of A549/DDP in a time-dependent manner by reducing GST-π expression to increase the accumulation of DDP. The effect of CIK cells on re-sensitizing lung cancer cells to the chemotherapy drug was partially dependent on the secretion of IFN-γ.

13.
Zhongguo Fei Ai Za Zhi ; 20(11): 761-768, 2017 Nov 20.
Article in Chinese | MEDLINE | ID: mdl-29167006

ABSTRACT

BACKGROUND: The efficacy of second or third-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients is low. The use of targeted drugs brings survival benefit for some patients. Apatinib, as a novel small molecule antiangiogenic drug, has demonstrated satisfactory anticancer activity across a broad range of malignancies. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced NSCLC after first-line treatment failure. METHODS: A retrospective study of 128 patients was conducted to evaluate the safety, short-term efficacy and survival status with different regimens. Kaplan-Meier method and Cox regression model were used for analysis. RESULTS: Compared with chemotherapy alone, the median progression free survival (PFS) in apatinib monotherapy, chemotherapy alone and apatinib combined with chemotherapy were 3.0 (P=0.381), 3.7 and 6.0 months (P<0.001), respectively. The median overall survival (OS) were 6.0 (P=0.494), 6.5 and 9.0 months (P=0.001), respectively. The incidence of adverse events in grades 3-4 were 18.5%, 15.8% and 16.0%, respectively (P=0.947). Different treatment regimens (P=0.018) and performance status (PS)(P<0.001) were the independent factors of PFS. The smoking history (P=0.014), treatment regimens (P=0.002) and PS (P<0.001) were independent influencing factors of OS. CONCLUSIONS: Apatinib has a good security. After first-line treatment failure of lung cancer, chemotherapy combined with apatinib in second or third-line is beneficial in PFS and OS when compared with chemotherapy alone. But when making comparison between apatinib monotherapy and chemotherapy alone, there is no significant difference in PFS and OS. Patients who never smoke or has a better PS or use combination therapy have longer survival time.
.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Pyridines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Retrospective Studies
14.
Melanoma Res ; 27(6): 601-606, 2017 12.
Article in English | MEDLINE | ID: mdl-29016386

ABSTRACT

Primary malignant melanoma arising in an ovarian cystic teratoma is exceedingly rare event with an estimated incidence of 0.2-0.8%. So far, there have been approximately only 47 relevant reports. We report a case of primary malignant melanoma of the ovary arising in a cystic teratoma here. Moreover, we review systematically the disease from the following aspects, that origin, clinical characteristics, accessory examination, pathological features, diagnosis, differential diagnosis, treatment, prognosis.


Subject(s)
Melanoma/etiology , Ovarian Neoplasms/complications , Teratoma/complications , Adult , Female , Humans , Immunohistochemistry , Melanoma/pathology , Prognosis
15.
Onco Targets Ther ; 9: 2675-82, 2016.
Article in English | MEDLINE | ID: mdl-27226730

ABSTRACT

PURPOSE: Telomere shortening occurs in tumor tissues and peripheral blood lymphocytes of many common human malignancies, including lung cancer, but its variation in T-cells has never been investigated. Thus, the aim of this study was to assess telomere length in T-cells and its correlation with the clinical characteristics of patients with lung cancer. PATIENTS AND METHODS: A total of 40 patients with lung cancer but without prior cancer history and 25 healthy individuals were selected. T-cells were isolated and their telomere lengths were measured using quantitative real-time polymerase chain reaction methods. RESULTS: Telomere length in T-cells was significantly shorter in patients with lung cancer than in controls (P<0.001). Shorter telomere length was significantly associated with increased clinical stage (P=0.008) and distant metastasis (P=0.028). Naïve T-cells from patients with lung cancer had significantly decreased telomere length when compared with those from controls (P=0.012). CONCLUSION: The shortened telomere length in T-cells occurred in naïve T-cells and might be related to lung cancer progression.

16.
Clin Colorectal Cancer ; 15(3): 228-35, 2016 09.
Article in English | MEDLINE | ID: mdl-27052743

ABSTRACT

BACKGROUND: This randomized clinical study was conducted to evaluate the therapeutic benefits of cytokine-induced killer (CIK) cell immunotherapy in combination with chemotherapy in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Sixty-one patients in group 1 (cell therapy group) received autologous CIK cell immunotherapy in combination with chemotherapy (5-Fluorouridine, leucovorin and oxaliplatin [FOLFOX4] plan). Another 61 patients in group 2 (the control group) received chemotherapy (FOLFOX4 plan) alone. The primary study end points were overall survival (OS) and progression-free survival (PFS). The secondary end points were treatment response and adverse events. RESULTS: The 3-year PFS and OS in group 1 were 20% and 48%, respectively, compared with 13% and 23%, respectively, in group 2 (P = .131 and P < .001, respectively). The median OS in group 1 was significantly increased compared with that in group 2 (OS, 36 vs. 16 months; P < .001). Furthermore, there was a trend toward superior PFS in group 1 compared with that in group 2 (PFS, 16 vs. 10 months; P = .072). Using univariate analysis, we found that Karnofsky performance status <80, number of metastases >1, and increased platelet levels were significantly associated with poorer prognosis in group 1. Alternatively, the cycle count of CIK cell treatment was significantly associated with good prognosis in group 1. Toxicity was mild in patients who received CIK therapy. CONCLUSION: This study shows that CIK cell immunotherapy in combination with chemotherapy is well tolerated and improves the OS of mCRC patients.


Subject(s)
Adenocarcinoma/therapy , Colorectal Neoplasms/therapy , Cytokine-Induced Killer Cells/transplantation , Immunotherapy/methods , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Area Under Curve , Combined Modality Therapy/methods , Disease-Free Survival , Female , Humans , Immunotherapy/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , ROC Curve
17.
Hum Immunol ; 76(9): 615-21, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26385479

ABSTRACT

Historically, the pivotal role of B cells or B lymphocytes in immunity has been attributed to the production of antibodies. They were also demonstrated to present antigens to T cells and to secrete cytokines, thereby acting as positive regulators in immune responses. A series of studies on autoimmune diseases, however, led researchers to find a unique subset of B cells, later described as "regulatory B cells" (Bregs), that has the ability to suppress immune responses. Bregs occur not only in autoimmune diseases, but also in inflammation and transplantation. Furthermore, recently published literatures suggested that Bregs contributed to the growth and metastasis of certain cancers. In this review, we will discuss these unique subsets of B cells in different kinds of disorders, with particular emphasis on the mechanisms of their immunoregulatory role that were collected from mice and humans.


Subject(s)
B-Lymphocytes, Regulatory/immunology , B-Lymphocytes, Regulatory/metabolism , Animals , Antigens, Surface/metabolism , B-Lymphocytes, Regulatory/cytology , Cell Differentiation , Cytokines/metabolism , Humans , Immune System Diseases/genetics , Immune System Diseases/immunology , Immune System Diseases/metabolism , Immune System Diseases/therapy , Immunomodulation , Immunotherapy , Molecular Targeted Therapy , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/metabolism , Phenotype , Signal Transduction
18.
Cancer Biol Med ; 12(2): 126-39, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26175928

ABSTRACT

OBJECTIVE: A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. METHODS: Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. CONCLUSION: K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

19.
Tumour Biol ; 36(5): 3159-69, 2015 May.
Article in English | MEDLINE | ID: mdl-25828146

ABSTRACT

The hallmark of tumor microenvironment is that it makes up of numerous immunomodulatory cells and factors which exert essential roles in immunoprotection and immunosuppression in addition to tumor cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells reported to promote immunosuppression and angiogenesis and facilitate tumor metastasis and invasion. The wide scope of MDSCs functional activities make these cells promising targets for effective cancer treatments. In this review, we briefly discuss the origin, subpopulation, and functions of MDSCs, as well as the potential to target these cells for therapeutic benefit. We focus on the underlying molecular mechanisms of these drugs targeting MDSCs, mainly from the standpoint of molecules related to drug targets.


Subject(s)
Antineoplastic Agents/pharmacology , Myeloid Cells/drug effects , Neoplasms/drug therapy , Animals , Antineoplastic Agents/therapeutic use , Humans , Molecular Targeted Therapy , Signal Transduction/drug effects , Tumor Microenvironment
20.
J Cancer Res Clin Oncol ; 141(8): 1371-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25555465

ABSTRACT

PURPOSES: Osteopontin (OPN), an extracellular matrix-secreted phosphorylated glycoprotein, has been reported overexpressed in many solid tumors. As an important part of lung cancer, the high recurrence of non-small cell lung cancer (NSCLC) also attracted great attention of scientists. METHODS: In this study, we investigated the expression of OPN and the relationship with prognosis of NSCLC patients. We measured the expression of OPN among 163 NSCLC samples by immunohistochemical method and compared the expression of these 28 matched cDNA between tumor and peritumoral tissue by real-time polymerase chain reaction. RESULTS: We demonstrated that the percentages of positive OPN expression is 66.8 % and OPN expression in tumor site was much higher than the tissue adjacent to carcinoma (p = 0.0046). By further analysis, we found that OPN expression was significantly correlated with poor prognosis of NSCLC. Moreover, for early-stage patients, OS and DFS rates of OPN (-) group were significantly higher than OPN (+) group. For advanced-stage patients, OPN expression was only associated with OS rates. CONCLUSIONS: These results suggest that OPN is commonly expressed in NSCLC and may guide the evaluation of prognosis with NSCLC, especially for early-stage patients.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Osteopontin/metabolism , Adult , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/pathology , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Pneumonectomy , Prognosis , Treatment Outcome
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