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1.
Colloids Surf B Biointerfaces ; 238: 113909, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599076

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.


Subject(s)
Biomimetic Materials , Cell Membrane , Doxorubicin , Nanoparticles , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Doxorubicin/pharmacology , Doxorubicin/chemistry , Nanoparticles/chemistry , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Membrane/drug effects , Animals , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Dendrimers/chemistry , Mice , Cell Line, Tumor , Drug Delivery Systems , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/administration & dosage , Cell Proliferation/drug effects , Mice, Nude , Mice, Inbred BALB C , Biomimetics , Particle Size
2.
J Adv Res ; 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38499244

ABSTRACT

INTRODUCTION: Immunotherapy has unprecedentedly opened up a series of neoteric tactics for cancer treatment. As a burgeoning approach, chemo-immunotherapy has innovatively expanded the accomplishments of conventional chemotherapeutic agents for cancer governing. OBJECTIVES: An efficacious chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle (NP) integrated tumor immunogenic cell death (ICD) and immunoagonist was developed as a watertight "in situ" vaccine for cancer therapy through convenient intratumoral administration with minimized systemic toxicity. METHODS: Chemical-modified pH-sensitive cis-aconityl-doxorubicin (CAD) and immunoadjuvant unmethylated cytosine-phosphate-guanine (CpG) were co-packaged by polycationic polyethylenimine (PEI) though electrostatic-interaction to construct PEI/CpG/CAD NP. By intratumoral injection, this positively charged NP could be detained at tumor site and endocytosed by tumor cells effortlessly. Then, doxorubicin was released through cis-aconityl cleavage induced by endosomal-acidity and further triggered tumor ICD, the moribund tumor cells could release damage-associated molecular patterns (DAMPs) to recruit dendritic cells (DCs). Meanwhile, the entire tumor debris derived into diversified antigens and cooperated with immunostimulatory CpG to excite DC maturation and activated comprehensive antitumor immunity. RESULTS: Prominent tumor suppression was achieved in aggressive mouse melanoma tumor model, which verified the feasibility and effectiveness of this minimalist CAD/CpG-codelivered NP. CONCLUSION: This study has provided a convenient and promising paradigm for potent cancer chemo-immunotherapy.

3.
Int J Biol Macromol ; 242(Pt 4): 125223, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37276908

ABSTRACT

Tumor vaccine has brought a new dawn for cancer immunotherapy, but disillusionary therapeutic outcomes have been achieved due to the inefficient in vivo vaccine delivery. Moreover, tumor cells customarily resort to various wily tricks to circumvent the recognition and sweeping of the immune system, the immune escape effect has badly aggravated the difficulty of cancer management. With respect to the foregoing, in this study, a promising combinational strategy which cooperated nanovaccine with immune escape inhibition was developed for synergistically enhancing the oncotherapy efficiency. On the one hand, natural polycationic macromolecule protamine (PRT) was utilized as the carrier to construct an antigen and adjuvant co-packaged nanovaccine for facilitating the ingestion in antigen-presenting cells, amplifying antigen cross-presentation and optimizing in vivo delivery. On the other hand, PD-L1 silence gene was selected and hitchhiked in a pH-responsive nanoparticle developed in our previous study. The therapeutic gene could be successfully delivered into the tumors to down-regulate PD-L1 expression and cripple tumor immune escape. The combination of nanovaccine with PD-L1 gene silence nanoparticle could synchronously stimulate antitumor immune responses and reduce immune escape, synergistically enhance the therapeutic efficiency. This study will furnish the prospective tactics for the research of cancer immunotherapy.


Subject(s)
Nanoparticles , Neoplasms , Humans , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Prospective Studies , Neoplasms/drug therapy , Immunotherapy/methods
6.
Biomark Res ; 11(1): 21, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36803645

ABSTRACT

BACKGROUND: Pyrotinib, a novel irreversible tyrosine kinase inhibitor (TKI), has demonstrated promising antitumor activity to improve the overall response rate and progression-free survival (PFS) in patients with HER2-positive metastatic breast cancer (MBC). However, the survival data of pyrotinib or pyrotinib plus capecitabine in HER2-positive MBC remains scarce. Thus, we summarized the updated individual patient data from the phase I trials of pyrotinib or pyrotinib plus capecitabine, to provide a cumulative assessment on long-term outcomes and associated biomarker analysis of irreversible TKIs in HER2-positive MBC patients. METHODS: We performed a pooled analysis of the phase I trials for pyrotinib or pyrotinib plus capecitabine based on the updated survival data from individual patients. Next-generation sequencing was performed on circulating tumor DNA for predictive biomarkers. RESULTS: A total of 66 patients were enrolled, including 38 patients from the phase Ib trial for pyrotinib and 28 patients from the phase Ic trial for pyrotinib plus capecitabine. The median follow-up duration was 84.2 months (95% CI: 74.7-93.7 months). The estimated median PFS in the entire cohort was 9.2 months (95% CI: 5.4-12.9 months) and median OS was 31.0 months (95% CI: 16.5-45.5 months). The median PFS was 8.2 months in the pyrotinib monotherapy cohort and 22.1 months in the pyrotinib plus capecitabine group, while the median OS was 27.1 months in the pyrotinib monotherapy group and 37.4 months in the pyrotinib plus capecitabine group. Biomarker analysis suggested that the patients harbored concomitant mutations from multiple pathways in HER2-related signaling network (HER2 bypass signaling pathways, PI3K/Akt/mTOR pathway and TP53) were observed with significantly poorer PFS and OS when compared to those with none or one genetic alteration (median PFS, 7.3 vs. 26.1 months, P = 0.003; median OS, 25.1 vs. 48.0 months, P = 0.013). CONCLUSIONS: The updated survival results based on individual patient data from the phase I trials of pyrotinib-based regimen revealed promising PFS and OS in HER2-positive MBC. Concomitant mutations from multiple pathways in HER2-related signaling network may be a potential efficacy and prognosis biomarker for pyrotinib in HER2-positive MBC. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT01937689, NCT02361112).

7.
ACS Appl Mater Interfaces ; 14(45): 50475-50484, 2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36327132

ABSTRACT

Tumor-associated macrophages (TAMs) widely exist in the solid tumors, which participate in the entire course of tumor development and execute momentous impacts. Therefore, manipulating TAMs has been identified as an expecting strategy with immense potential for cancer therapy. Herein, a nanodrug delivery system was leveraged for simultaneously targeting tumor cells and M2-type TAMs for efficient colon cancer therapy. The broad-spectrum anticancer chemotherapeutic drug doxorubicin (DOX) was hitchhiked in a mannose-modified bovine serum albumin (MAN-BSA) carrier. The DOX@MAN-BSA nanodrug delivery system was verified to possess feasible physical performances for unhindered systemic circulation and active targeting on colon tumors. DOX@MAN-BSA nanoparticles could be preferentially swallowed by colon tumor cells and M2 TAMs through mannose receptor-mediated endocytosis. Further in vivo antitumor therapy in CT26 colon tumor-bearing mice has achieved remarkable suppression efficacy with satisfactory biosafety. Leveraging the nanodrug delivery system for simultaneously targeting tumor cells and M2 TAMs has contributed a feasible strategy to collaboratively repress the malignant tumor cells and the collusive M2 TAMs for efficient cancer therapy.


Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Nanoparticles , Mice , Animals , Tumor-Associated Macrophages , Macrophages/pathology , Drug Delivery Systems , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Nanoparticles/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mannose , Serum Albumin, Bovine , Cell Line, Tumor , Tumor Microenvironment
8.
J Colloid Interface Sci ; 624: 734-746, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-35696791

ABSTRACT

Studies have shown that disulfiram (DSF) can combine with Cu2+ to form bis(N, N-diethyldithiocarbamate) copper(II) complex (CuET) as antitumor drugs. However, there is insufficient endogenous Cu2+ dose to eradicate cancer cells selectively. Inspired by the buffet, we use Cu2+ doped hollow zeolitic imidazolate framework nanoparticles (HZIFCu) as the carrier and equipped with DSF and indocyanine green (ICG) and targeted by folic acid (FA) (D&I@HZIFCu-FA) to enhance DSF-based cancer therapy. D&I@HZIFCu-FA could effectively supply Cu2+ by a buffet-style, assisting the "DSF-to-CuET" transformation in the tumor. Additionally, self-supply Cu2+ could convert H2O2 into ·OH by triggering a Fenton-like reaction for chemo-dynamic therapy, and ICG achieves photothermal therapy for tumors under laser irradiation. This work provides a buffet-style for Cu2+ to make DSF a strong candidate for cancer treatment by combining chemotherapy, chemo-dynamic therapy, and photothermal therapy and inspires more research about its applications in tumor therapy.


Subject(s)
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Copper , Disulfiram/pharmacology , Hydrogen Peroxide , Neoplasms/drug therapy
9.
Future Oncol ; 18(17): 2127-2139, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35414207

ABSTRACT

Aim: To identify clinical and genetic variants associated with early-onset cardiac toxicity with a low cumulative dose of chemotherapy drugs in breast cancer. Methods: A total of 388 recruited patients completed routine blood, liver and kidney function, D-dimer, troponin T, brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, ECG and echocardiography tests before and after adjuvant chemotherapy. 25 single-nucleotide polymorphisms (SNPs) were tested. Results: A total of 277 adjuvant chemotherapy-related cardiac toxicity events were recorded in 180 patients (46.4%). Anthracycline-containing chemotherapy (odds ratio: 1.848; 95% CI: 1.135-3.008; p = 0.014) and the SLC28A3 rs885004 GG genotype (odds ratio: 2.034; 95% CI: 1.189-3.479; p = 0.010) were found to be associated with overall cardiac toxicity. The final predictive risk model consisting of clinical risk factors and SNPs was better than SNP alone (p = 0.006) or clinical risk factor alone (p = 0.065). Conclusion: On the basis of clinical factors, a prediction model with genetic susceptibility factors can better predict early-onset cardiac toxicity.


Subject(s)
Breast Neoplasms , Cardiotoxicity , Anthracyclines/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cardiotoxicity/etiology , Cardiotoxicity/genetics , Chemotherapy, Adjuvant/adverse effects , Female , Humans , Natriuretic Peptide, Brain/therapeutic use , Stroke Volume
10.
Cancer Med ; 11(14): 2767-2778, 2022 07.
Article in English | MEDLINE | ID: mdl-35393784

ABSTRACT

PURPOSE: We used targeted capture sequencing to analyze TP53-mutated circulating tumor DNA (ctDNA) in metastatic breast cancer patients and to determine whether TP53 mutation has predictive value for anti-human epidermal growth factor receptor 2 (HER2) treatment for in HER2 amplification-positive patients (HER2+) and HER2 mutation-positive, amplification-negative (HER2-/mut) patients. PATIENTS AND METHODS: TP53 mutation features were analyzed in the Geneplus cohort (n = 1184). The MSK-BREAST cohort was used to explore the value of TP53 mutation in predicting anti-HER-2 antibody efficacy. Sequencing of ctDNA in phase Ib, phase Ic, phase II clinical trials of pyrotinib (HER2+ patients), and an investigator-initiated phase II study of pyrotinib (HER2-/mut patients) were performed to analyze the relationships between TP53 mutation and prognosis for HER2 TKIs. The MSK-BREAST cohort, MutHER, and SUMMIT cohort were used for verification. RESULTS: TP53 mutations were detected in 53.1% (629/1184) of patients in the Geneplus cohort. The TP53 mutation rate was higher in HR-negative (p < 0.001) and HER2 amplification-positive (p = 0.015) patients. Among patients receiving anti-HER2 antibody therapy, those whose tumors carried TP53 mutations had a shorter PFS (p = 0.004). However, the value of TP53 mutation in predicting HER2 TKI response was inconsistent. In HER2+ patients, no difference in PFS was observed among patients with different TP53 statuses in the combined analysis of the pyrotinib phase Ib, phase Ic, and phase II clinical trials (p = 1.00) or in the MSK-BREAST cohort (p = 0.62). In HER2-/mut patients, TP53 mutation-positive patients exhibited a trend toward worse prognosis with anti-HER2 TKI treatment than TP53-wild-type patients in our investigator-initiated phase II study (p = 0.15), and this trend was confirmed in the combined analysis of the MutHER and SUMMIT cohorts (p = 0.01). CONCLUSIONS: TP53 mutation can be used to identify biomarkers of anti-HER2 antibody drug resistance in HER2+ patients and HER2 TKI resistance in HER2-/mut patients.


Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Biomarkers, Tumor/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Circulating Tumor DNA/genetics , Female , Humans , Mutation , Prognosis , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Tumor Suppressor Protein p53/genetics
11.
J Adv Res ; 35: 49-60, 2022 01.
Article in English | MEDLINE | ID: mdl-35003793

ABSTRACT

Introduction: Tumor vaccine has been a research boom for cancer immunotherapy, while its therapeutic outcome is severely depressed by the vulnerable in vivo delivery efficiency. Moreover, tumor immune escape is also another intractable issue, which has badly whittled down the therapeutic efficiency. Objectives: Our study aims to solve the above dilemmas by cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy. Methods: The minimalist antigen and adjuvant co-delivery nanovaccine was developed by employing natural polycationic protamine (PRT) to carry the electronegative ovalbumin (OVA) antigen and unmethylated Cytosine-phosphorothioate-Guanine (CpG) adjuvant via convenient chemical bench-free "green" preparation without chemical-synthesis and no organic solvent was required, which could preserve the immunological activities of the antigens and adjuvants. On that basis, PD-1 antibody (aPD-1) was utilized to block the tumor immune escape and cooperate with the nanovaccine by maintaining the tumoricidal-activity of the vaccine-induced T cells. Results: Benefited from the polycationic PRT, the facile PRT/CpG/OVA nanovaccine displayed satisfactory delivery performance, involving enhanced cellular uptake in dendritic cells (DCs), realizable endosomal escape and promoted stimulation for DCs' maturation. These features would be helpful for the antitumor immunotherapeutic efficiency of the nanovaccine. Furthermore, the cooperation of the nanovaccine with aPD-1 synergistically improved the immunotherapy outcome, profiting by the cooperation of the "T cell induction" competency of the nanovaccine and the "T cell maintenance" function of the aPD-1. Conclusion: This study will provide new concepts for the design and construction of facile nanovaccines, and contribute valuable scientific basis for cancer immunotherapy.


Subject(s)
Cancer Vaccines , Nanoparticles , Neoplasms , Animals , Immunotherapy , Mice , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor
12.
Breast ; 61: 129-135, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34995922

ABSTRACT

BACKGROUND: To observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population. METHODS: The China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using log-rank test. RESULTS: The number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS. CONCLUSION: In real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.


Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/drug therapy , Female , Hormones/therapeutic use , Humans , Palliative Care , Receptor, ErbB-2
13.
Cancer Innov ; 1(2): 119-123, 2022 Aug.
Article in English | MEDLINE | ID: mdl-38090648

ABSTRACT

This pooled analysis explored the possibility and potential of pyrotinib plus capecitabine as a first-line regimen in relapsed or metastatic HER2-positive breast cancer patients who received prior adjuvant or neoadjuvant chemotherapy with trastuzumab and discussed the potential treatment options for these patients, especially for the patients relapsed during or within 6 months after adjuvant trastuzumab.

14.
J Colloid Interface Sci ; 605: 752-765, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34365311

ABSTRACT

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.


Subject(s)
Hyperthermia, Induced , Metal Nanoparticles , Nanoparticles , Neoplasms , Cell Line, Tumor , Gold , Humans , Neoplasms/therapy , Phototherapy , Tumor Microenvironment
15.
J Oncol ; 2021: 4891936, 2021.
Article in English | MEDLINE | ID: mdl-34887923

ABSTRACT

BACKGROUND: Breast cancer has both aggressive clinicopathological characteristics and a poor prognosis in young females. However, limited information is available for breast cancer in Chinese females aged ≤25 years. Therefore, we aimed to explore prognostic factors for invasive disease-free (iDFS) and overall survival (OS) among breast cancer patients aged ≤25 years. METHODS: We retrospectively analyzed data from 174 Chinese females aged ≤25 years with invasive breast cancer treated in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1, 1999, to December 31, 2018. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. RESULTS: The median follow-up time was 75 months (ranging from 1 to 236 months). Breast cancer patients aged ≤25 years exhibited aggressive clinicopathological characteristics, including advanced tumor stage (21.8%), lymph node metastasis (47.1%), lymphovascular invasion (24.1%), estrogen receptor negativity (44.3%), progesterone receptor (PR) negativity (42.5%), and triple-negative breast cancer (25.3%). Among them, 50 cases had locoregional recurrence and metastasis, 20 had bilateral invasiveness, and 33 had breast cancer-specific deaths. Cox multivariate analysis identified that diagnosis delay, PR status, and radiotherapy were significant prognostic factors for both iDFS and OS (P < 0.05). The risk of recurrence and metastasis was five times higher in N3 than in N0 (HR: 6.778, 95% CI: 2.268-17.141, P < 0.001). Patients with lymphovascular invasion had a threefold increase in the risk of breast cancer-specific death (HR: 4.217, 95% CI: 1.956-9.090, P < 0.001). No differences were observed between mastectomy and breast-conserving surgery (BCS) plus radiotherapy for iDFS or OS (iDFS: χ 2 = 0.678, P=0.410; OS: χ 2 = 0.165, P=0.685). CONCLUSIONS: Breast cancer in females ≤25 years old was associated with aggressive clinical features and a worse prognosis. Young females with breast lumps should receive timely diagnosis and treatment. Young breast cancer patients with lymphovascular invasion, PR-negative status, and lymph node metastasis have an increased risk of experiencing recurrence and metastasis and should hence be closely monitored. Age at diagnosis should not be the sole deciding factor for surgical treatment methods.

16.
BMC Cancer ; 21(1): 1330, 2021 Dec 14.
Article in English | MEDLINE | ID: mdl-34906122

ABSTRACT

BACKGROUND: We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population. METHODS: We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses. RESULTS: Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients. CONCLUSIONS: Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.


Subject(s)
Breast Neoplasms/mortality , Lung Neoplasms/mortality , Neoplasms, Multiple Primary/mortality , Asian People/ethnology , Breast Neoplasms/ethnology , Breast Neoplasms/pathology , China/epidemiology , Female , Humans , Incidence , Logistic Models , Lung Neoplasms/ethnology , Lung Neoplasms/secondary , Middle Aged , Neoplasms, Multiple Primary/ethnology , Neoplasms, Multiple Primary/pathology , Proportional Hazards Models , Risk Factors , Survival Rate
17.
Chin Med J (Engl) ; 135(3): 261-267, 2021 Dec 22.
Article in English | MEDLINE | ID: mdl-34935688

ABSTRACT

ABSTRACT: Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.


Subject(s)
Antineoplastic Agents, Immunological , Antineoplastic Agents , Breast Neoplasms , Immunoconjugates , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Breast Neoplasms/drug therapy , Female , Humans , Immunoconjugates/therapeutic use , Receptor, ErbB-2
18.
J Nanobiotechnology ; 19(1): 335, 2021 Oct 24.
Article in English | MEDLINE | ID: mdl-34689765

ABSTRACT

Photothermal therapy (PTT), which converts light energy to heat energy, has become a new research hotspot in cancer treatment. Although researchers have investigated various ways to improve the efficiency of tumor heat ablation to treat cancer, PTT may cause severe damage to normal tissue due to the systemic distribution of photothermal agents (PTAs) in the body and inaccurate laser exposure during treatment. To further improve the survival rate of cancer patients and reduce possible side effects on other parts of the body, it is still necessary to explore PTAs with high selectivity and precise treatment. In this review, we summarized strategies to improve the treatment selectivity of PTT, such as increasing the accumulation of PTAs at tumor sites and endowing PTAs with a self-regulating photothermal conversion function. The views and challenges of selective PTT were discussed, especially the prospects and challenges of their clinical applications.


Subject(s)
Neoplasms/therapy , Photothermal Therapy , Animals , Humans , Mice
19.
Cancer Cell ; 39(12): 1578-1593.e8, 2021 12 13.
Article in English | MEDLINE | ID: mdl-34653365

ABSTRACT

In triple-negative breast cancer (TNBC), the benefit of combining chemotherapy with checkpoint inhibitors is still not very clear. We utilize single-cell RNA- and ATAC-sequencing to examine the immune cell dynamics in 22 patients with advanced TNBC treated with paclitaxel or its combination with the anti-PD-L1 atezolizumab. We demonstrate that high levels of baseline CXCL13+ T cells are linked to the proinflammatory features of macrophages and can predict effective responses to the combination therapy. In responsive patients, lymphoid tissue inducer (LTi) cells, follicular B (Bfoc) cells, CXCL13+ T cells, and conventional type 1 dendritic cells (cDC1) concertedly increase following the combination therapy, but instead decrease after paclitaxel monotherapy. Our data highlight the importance of CXCL13+ T cells in effective responses to anti-PD-L1 therapies and suggest that their reduction by paclitaxel regimen may compromise the clinical outcomes of accompanying atezolizumab for TNBC treatment.


Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Single-Cell Analysis/methods , Triple Negative Breast Neoplasms/drug therapy , Female , Humans , Immune Checkpoint Inhibitors/pharmacology
20.
Nanoscale ; 13(41): 17218-17235, 2021 Oct 28.
Article in English | MEDLINE | ID: mdl-34643196

ABSTRACT

Chemotherapy has been a conventional paradigm for cancer treatment, and multifarious chemotherapeutic drugs have been widely employed for decades with significant performances in suppressing tumors. Moreover, some of the antitumor chemotherapeutic agents, such as doxorubicin (DOX), oxaliplatin (OXA), cyclophosphamide (CPA) and paclitaxel (PTX), can also tackle tumors through the induction of immunogenic cell death (ICD) in tumor cells to trigger specific antitumor immune responses of the body and improve chemotherapy efficacy. In recent years, chemo-immunotherapy has attracted increasing attention as one of the most promising combination therapies to struggle with malignant tumors. Many effective antitumor therapies have benefited from the successful induction of ICD in tumors, which could incur the release of endogenous danger signals and tumor-associated antigens (TAAs), further stimulating antigen-presenting cells (APCs) and ultimately initiating efficient antitumor immunity. In this review, several well-characterized damage-associated molecular patterns (DAMPs) were introduced and the progress of ICD induced by representative chemotherapeutic drugs for nanomedicine-based chemo-immunotherapy was highlighted. In addition, the combination strategies involving ICD cooperated with other therapies were discussed. Finally, we shared some perspectives in chemotherapeutic drug-induced ICD for future chemo-immunotherapy. It was hoped that this review would provide worthwhile presentations and enlightenments for cancer chemo-immunotherapy.


Subject(s)
Antineoplastic Agents , Neoplasms , Pharmaceutical Preparations , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Humans , Immunogenic Cell Death , Immunotherapy , Nanomedicine , Neoplasms/drug therapy
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