Surgery is a Viable Treatment Option for Stage IE Primary Thyroid Lymphoma.

BACKGROUND: Stage IE primary thyroid lymphoma (PTL) has been diagnosed in approximately half of patients with PTL; however, the optimal treatment for stage IE PTL has not yet been established. METHODS: Stage IE PTL patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2019. Thereafter, the disease-specific survival (DSS) and treatment modalities (surgery alone, surgery + radiotherapy (RT) and/or chemotherapy (CT), and RT and/or CT) of these patients were compared by Kaplan-Meier curves and log-rank test after propensity score matching (PSM). Additionally, patients with PTL from the Affiliated Sixth People's Hospital of the Shanghai Jiao Tong University and School of Medicine (Shanghai, China) between 2007 and 2022 were retrospectively analyzed as an external cohort. RESULTS: Among the 1596 patients with PTL from the SEER database, 842 were identified as patients with stage IE PTL, with an average follow-up period of 7.8 years. Pairwise analysis after PSM revealed no significant difference between the DSS of the three treatment groups. A total of 38 patients with PTL were identified in the external cohort, with an average follow-up period of 3.4 years. Compared with the RT and/or CT group, the surgery-alone group showed no significant difference in the incidence of hypothyroidism (p = 0.161) but had significantly fewer treatment-related complications (p = 0.021), shorter treatment duration (p < 0.001), and lower treatment costs (p = 0.025). CONCLUSIONS: The results of our study demonstrate that surgery is a viable treatment option for patients with stage IE PTL.

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis.

CONTEXT: Multifocality and bilaterality are common in patients with papillary thyroid microcarcinoma (PTMC). However, their clinical behaviours and prognostic implications remain controversial. OBJECTIVE: To investigate the relationship between multifocality and classically aggressive characteristics and outcomes in patients with PTMC. METHODS: Clinical data of 3005 patients with PTMC were retrospectively reviewed at a tertiary medical centre. The role of unilateral and bilateral multifocality in aggressive characteristics and clinical outcomes of PTMC was evaluated using propensity score matching (PSM). RESULTS: A total of 573 patients had bilateral multifocal disease (B-MFD), 272 had unilateral multifocal disease (U-MFD), and 2160 had unifocal disease (UFD). Univariate analysis showed that patients in the multifocal disease (MFD) groups showed significantly different characteristics compared to patients in the UFD group in terms of age, chronic lymphocytic thyroiditis (CLT), follicular variant PTMC, tumour diameter, aggressive growth, including extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM), and TNM stage, and underwent radioactive iodine (RAI) therapy. Further stratified analysis revealed that patients in the B-MFD group reflected the differences between the MFD and UFD groups. However, those in the U-MFD group showed slight differences only in sex, CLT and cell subtypes, compared to the UFD group. In addition, PSM indicated differences in ETE, CLNM and LLNM between the B-MFD and UFD groups (p < .001), while only ETE differed between the U-MFD and UFD groups (p < .001). After a median follow-up period of 60 months, no difference was observed in recurrence-free survival between the UFD and B-MFD (p = .294) or U-MFD (p = .603) groups using PSM. CONCLUSION: This propensity score matching analysis provides strong evidence that bilateral multifocality, rather than unilateral multifocality, should be considered as an aggressive marker at presentation, and neither is an independent prognostic factor for clinical outcome in PTMC.

Comparison of Lobectomy and Total Thyroidectomy in Unilateral Papillary Thyroid Microcarcinoma Patients with Ipsilateral Lateral Lymph Node Metastasis Without Gross Extrathyroidal Extension.

BACKGROUND: Lateral lymph node metastasis (LLNM) occurs in a few of papillary thyroid microcarcinoma (PTMC) cases by the time of diagnosis. Total thyroidectomy (TT) is recommended in the 2015 American Thyroid Association guidelines as the initial surgical procedure for thyroid carcinoma patients with clinically apparent cervical lymph node metastasis. However, none of the controlled studies have focused on the proper extent of surgery for patients who have PTMC with concomitant LLNM without gross extrathyroidal extension (ETE). METHODS: A total of 2373 consecutive patients with PTMC were retrospectively reviewed. Finally, 129 unilateral PTMC patients with ipsilateral LLNM without gross ETE were enrolled in this study and classified into two groups: those who underwent unilateral lobectomy (LT) plus lymph node dissection (LND) (Group I) and those who underwent TT plus LND (Group II). Surgical outcomes and recurrence-free survival (RFS) during the follow-up period were compared between the two groups. RESULTS: There were 62 patients in Group I and 67 patients in Group II. Cases in Group II had a longer median operation time (150 min vs. 120 min, p < 0.001) and a higher incidence of postoperative hypoparathyroidism (p < 0.001), especially permanent hypoparathyroidism, than cases in Group I. But the RFS showed no statistically significant difference (p = 0.6005) between the two groups during a median follow-up period of 60 months. CONCLUSION: Thyroid LT alone plus ipsilateral LND may be an optimum initial procedure for unilateral PTMC patients with ipsilateral LLNM without gross ETE. A long-term follow-up, prospective, randomized controlled trial is warranted.

ZNRF3 is downregulated in papillary thyroid carcinoma and suppresses the proliferation and invasion of papillary thyroid cancer cells.

Zinc and ring finger 3 (ZNRF3) is a transmembrane E3 ubiquitin ligase that has emerged as an important regulator of cancer development; however, its cancer-related function remains controversial. Here, we investigated the possible role of ZNRF3 in thyroid carcinoma (TC). We found that ZNRF3 is downregulated in papillary thyroid carcinoma (PTC) compared to normal thyroid tissues and inversely correlated with the degree of cell differentiation. Overexpression of ZNRF3 significantly suppressed cell malignant behaviors, including cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Consistent with recent studies showing that ZNRF3 is involved in the Wnt/ß-catenin pathway, ZNRF3 overexpression negatively regulated ß-catenin activation, modulating PTC cell behaviors. Clinical specimens revealed a significant inverse correlation between ZNRF3 and ß-catenin mRNA levels. Taken together, these results provide insight into a potential tumor suppressor role of ZNRF3 in PTC progression, and may have potential clinical relevance for the prognosis and treatment of PTC.

Correction: MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

[This corrects the article DOI: 10.18632/oncotarget.9530.].

The Prognosis of Skip Metastasis in Papillary Thyroid Microcarcinoma Is Better Than That of Continuous Metastasis.

CONTEXT: A few papillary thyroid microcarcinomas (PTMCs) may have skip metastasis (SLNM), but the risk factors remain controversial and the prognosis is unclear. OBJECTIVES: To investigate the incidence, lymph node metastasis (LNM) patterns, risk factors, and prognosis of SLNM in PTMCs. METHODS: We reviewed the medical records of PTMC patients who underwent thyroid surgery in our institution. Analyses of risk factors were performed for SLNM. Recurrence-free survival (RFS) of SLNM, central lymph node metastasis (CLNM), and continuous metastasis (CLNM and lateral lymph node metastasis [CLNM + LLNM]) were compared after propensity score matching (PSM). RESULTS: SLNM was detected in 1.7% (50/3923) and frequently involved level III (66.7%). Compared with CLNM + LLNM, SLNM had more LNM at a single level (P < 0.01) and less LNM at 2 levels (P < 0.05). A tumor size of 0.5 to 1 cm (odds ratio [OR], 2.26; 95% CI, 1.27-4.00) and location in the upper pole (OR, 3.30; 95% CI, 2.02-5.40) were independent risk factors for SLNM. A total of 910 (23.2%) PTMCs with LNM were included in the prognostic analysis. At a median follow-up of 60 months, the RFS of SLNM did not differ from that of CLNM (P = 0.10) but was significantly higher than that of CLNM + LLNM (P < 0.01) after using PSM. CONCLUSIONS: When the tumor size is 0.5 to 1 cm or its location is in the upper pole, we must remain vigilant to SLNM in PTMC. Because its prognosis is comparable to that of only CLNM and better than that of CLNM + LLNM, less intensive treatment should be considered.

Long-term outcomes and prognostic factors in papillary thyroid microcarcinoma patients with distant metastases.

PURPOSES: Distant metastasis from papillary thyroid microcarcinoma (PTMC) is extremely rare and the long-term outcomes and independent prognostic factors remain unclear. The present study aimed to investigate clinicopathological characteristics and evaluate the long-term outcomes and prognostic factors of PTMC patients with distant metastases (DM) who underwent surgery and radioactive iodine (131I) treatment. METHODS: We retrospectively reviewed the medical records of 13,441 patients with thyroid cancer (including 1697 cases with PTMC) who underwent 131I treatment at our institution between January 2008 and December 2019. PTMC patients with distant metastases with sufficient clinical follow-up data were enrolled in this cohort study. The overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method and the prognostic factors were assessed by Cox proportional hazards. RESULTS: Thirty-three PTMC patients with DM were enrolled in this study. The median follow-up was 75 months (range: 5-151 months). The 5-year and 10-year OS rates were 96.97 and 81.41%, respectively, and the 5-year and 10-year PFS rates were 90.46 and 69.68%, respectively. Multivariate analysis showed that male sex (P = 0.005), radioactive iodine refractory PTMC (P = 0.033), and symptomatic DM (P = 0.022) were significantly associated with worse 10-year PFS in PTMC patients with DM. No independent predictor related to poor 10-year OS was found in the present study. CONCLUSIONS: The prognosis of PTMC patients becomes worse after the development of DM. Male sex, radioactive iodine refractory PTMC, and symptomatic DM were identified as independent factors associated with PFS.

ARHGAP36 regulates proliferation and migration in papillary thyroid carcinoma cells.

The diagnosis and treatment of recurrence and metastasis in papillary thyroid carcinoma (PTC) are still clinical challenges. One of the key factors is the lack of specific diagnostic markers and therapeutic targets for recurrence and metastasis. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful approach to find specific biomarkers by dissecting expression profiling in human cancers at the resolution of individual cells. Here, we investigated cell profiles of the primary tumor and lymph node metastasis and paracancerous normal tissues in one PTC patient using scRNA-seq, and compared individual cell gene expression differences. The transcriptomes of 11,805 single cells were profiled, and malignant cells exhibited a profound transcriptional overlap between primary and metastatic lesions, but there were differences in the composition and quantity of non-malignant cells. ARHGAP36 was one of the genes that were highly expressed in almost all of the primary and metastatic malignant cells without non-malignant or normal follicular cells and was then confirmed by immunostaining in a sample cohort. Compared with the paracancerous normal tissue, the expression of ARHGAP36 in primary and metastatic carcinoma tissues was significantly higher as assayed by qRT-PCR. ARHGAP36 knockdown significantly inhibited the proliferation and migration of PTC cells in vitro and involved several proliferation and migration-associated signaling pathways by RNA seq. Our study demonstrated that ARHGAP36 is exclusively expressed in the malignant cells of primary PTC, as well as metastatic lesions, and regulates their proliferation and migration, meaning it can be used as a potential diagnostic marker and therapeutic target molecule.

Single-Cell Transcriptomic Analysis of Ecosystems in Papillary Thyroid Carcinoma Progression.

Background: Despite extensive research, the papillary thyroid carcinoma (PTC) ecosystem is poorly characterized and, in particular, locoregional progression. Available evidence supports that single-cell transcriptome sequencing (Sc-RNA seq) can dissect tumor ecosystems. Methods: Tissue samples from one PTC patient, including matched primary tumor (Ca), lymph node (LN) metastasis, and paracancerous tissue (PCa), were subjected to Sc-RNA seq with 10×Genomics. Dual-label immunofluorescence and immunohistochemistry were used to confirm the existence of cell subtypes in a separate cohort. Results: 11,805 cell transcriptomes were profiled, cell landscapes of PTC were composed of malignant follicular epithelial cells (MFECs), CD8+ and CD4+ T cells, B cells, vascular endothelial cells, fibroblasts and cancer-associated fibroblasts (CAFs). Between Ca and LN ecosystems, the proportions of MFEC and interstitial cells were similar, less than 1/25(229/6,694, 361/3,895), while the proportion of normal follicular epithelial cells (NFECs) and interstitial cells was > 2 in PCa (455/171). NFECs in PCa formed a separate cluster, while MFECs in Ca and LN exhibited a profound transcriptional overlap, and the interstitial cells among these samples had an overall concordance in their identity and representation, albeit with some distinctions in terms of the cell percentage per subset. A fraction of the B cell subpopulation in Ca expressed inhibitory receptors, while their respective ligand genes were clearly transcribed in T cell and malignant epithelial cell clusters, while some CD8+ T cells in both Ca and LN produced high levels of inhibitory receptors whose respective ligands were overexpressed in some CD4+ T cells. Three CAF subtypes in Ca and LN were identified, which may be due to mutual transitions. Conclusions: Our data provide new insights into the PTC ecosystem and highlight the differences in ecosystems in PTC progression, which updates our understanding of PTC biology and will improve individualized patient treatment.

Clinical Analysis of Risk Factors for Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Retrospective Study of 3686 Patients.

PURPOSE: To investigate the risk factors for cervical lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC). PATIENTS AND METHODS: In total, 3686 patients with PTMC who underwent initial surgery in Shanghai Jiao Tong University affiliated Sixth People's Hospital from January 2010 to December 2019 were retrospectively analyzed. Univariate and multivariate analyses were conducted to identify risk factors associated with cervical LNM. RESULTS: Male gender [odds ratio (OR) =1.420, P <0.001], age <55 years (OR =2.128, P <0.001), tumor size >6.5 mm (OR =2.112, P <0.001), lymphovascular invasion (LVI) (OR =2.110, P =0.016), multifocality (OR =1.358, P =0.022), extrathyroidal extension (ETE) (OR =1.598, P <0.001), and lateral LNM (LLNM) (OR =6.383, P <0.001) served as independent risk factors for central LNM (CLNM). Moreover, male gender (OR =1.668, P =0.001), tumor size >6.5 mm (OR =2.223, P <0.001), chronic lymphocytic thyroiditis (OR =1.402, P =0.021), LVI (OR =4.582, P <0.001), ETE (OR =1.393, P=0.023), and CLNM (OR =6.212, P <0.001) served as independent risk factors for LLNM. Furthermore, solitary PTMC with lesions in the upper third of the thyroid gland were more associated with LLNM than lesions in the other regions. CONCLUSION: This study suggests that meticulous evaluation of risk factors associated with LNM is required in order to guide the surgical treatment of PTMC patients in clinical practice.

A somatic mutation of RasGRP3 decreases Na+/I- symporter expression in metastases of radioactive iodine-refractory thyroid cancer by stimulating the Akt signaling pathway.

Mutation profiles of advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer have revealed the pathogenic roles of the established oncogenic mutations of BRAF and PI3KCA, but the involvement of other genes is presently unknown. In the present study, we performed whole-exome sequencing on 10 tissue samples of metastases of RAI-refractory differentiated thyroid cancers and identified a recurrent hot-spot mutation (c.1924G>T) in the RasGRP3 gene, which codes for Ras guanine nucleotide-releasing protein 3. This mutation was found to occur at a high frequency (20%) in samples of metastases of RAI-refractory differentiated thyroid cancers compared with other types of thyroid cancer. Overexpression of mutant RasGRP3 significantly promoted cell proliferation, migration, and invasiveness of 8505C and BHT101 cells compared with cells transfected with wild-type RasGRP3 or an empty vector. In addition, mutant RasGRP3 decreased the expression of sodium iodide symporter (NIS) and thyroid-stimulating hormone receptor (TSHR), reduced the iodine uptake ability, and increased Akt phosphorylation in thyroid cancer cells. Finally, we showed that LY294002, an inhibitor of PI3K/Akt signaling, attenuated the effects of mutant RasGRP3 on thyroid cancer cells. Thus, our study revealed that the c.1924G>T hot-spot mutation in RasGRP3 is a more frequent genetic alteration in metastases of RAI-refractory differentiated thyroid cancer. This mutant RasGRP3 activated the Akt pathway, promoted thyroid cancer cell proliferation and invasion, and reduced NIS expression and the iodine uptake ability.

Novel large-pore lightweight polypropylene mesh has better biocompatibility for rat model of hernia.

Abdominal wall hernias are repaired with tension-free prosthetic materials but there remains a foreign body response (FBR) to commonly used polypropylene mesh. Thus, we should optimize mesh materials to improve the patient outcomes after surgery. A polypropylene mesh was developed with wrap knitting technique. The physical, mechanical and biocompatible characteristics were tested in a rat abdominal hernia model and compared to ULTRAPRO and Easy Prosthesis. Polypropylene mesh of two pore sizes was developed (LP-WKPM and SP-WKPM). Compared with ULTRAPRO and Easy Prosthesis mesh, the novel mesh were lighter, thinner, and stronger (p < 0.05). Among the four implanted mesh types, there were fewer inflammatory cells and foreign body giant cells surrounding LP-WKPM fibers (p < 0.05), and significantly fewer mononuclear cells and less neovascularization between LP-WKPM fibers (p < 0.05) On day 15, 30 and 90 after implantation there were no differences in foreign body giant cells compared to 15 days after implantation (p>0.05). We developed a novel large-pore lightweight polypropylene mesh that produced less FBR and better biocompatibility in an abdominal wall hernia model. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1269-1275, 2018.

RasGRP3 controls cell proliferation and migration in papillary thyroid cancer by regulating the Akt-MDM2 pathway.

Accumulating evidence has shown that Ras guanylnucleotide releasing peptide 3 (RasGRP3) is up-regulated in several distinct cancer types; however, its role in papillary thyroid cancer (PTC) remains unclear. In this study, we demonstrate that RasGRP3 was overexpressed in PTC tissues and cell lines. Downregulation of RasGRP3 using small interfering (si) RNA significantly inhibited PTC cell proliferation and migration in vitro, and tumor growth in vivo, reflecting an oncogenic role of RasGRP3 in PTC. We subsequently identified that the expression of mouse double minute 2 homolog (MDM2) and phosphorylated Akt (p-Akt) was significantly decreased in RasGRP3-downregulated PTC cells. Overexpression of MDM2 attenuated the function of si-RasGRP3. Taken together, our data show that RasGRP3 exerts its oncogenic effect in PTC through Akt-mediated MDM2 activation. RasGRP3 may serve as a potential new therapeutic target for PTC.

MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in carcinogenesis. In this study, we investigated the biological function and mechanism of miR-613 in the regulation of papillary thyroid cancer (PTC) development. We found that miR-613 was downregulated in PTC cell lines and tissues, and overexpression of miR-613 significantly suppressed PTC cell growth, migration and invasion in vitro and inhibited tumor growth in vivo. We identified the gene for sphingosine kinase 2 (SphK2) as a direct target of miR-613. Overexpression of miR-613 significantly repressed SphK2 expression by directly targeting its 3'-untranslated regions (3'-UTR) and restoration of SphK2 reversed the inhibitory effects of miR-613 on PTC cell growth and invasion. Taken together, our results indicated that miR-613 functions as a tumor suppressor in PTC and its suppressive effect is mediated by repressing SphK2 expression.

Overexpression of Tbx3 is correlated with Epithelial-Mesenchymal Transition phenotype and predicts poor prognosis of colorectal cancer.

AIMS: To investigate the clinical significance of Tbx3 in colorectal cancer (CRC) and the possible association between Tbx3 expression and Epithelial- Transition Mesenchymal (EMT) phenotype. METHODS: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were employed to evaluate the expression of Tbx3 in 30 fresh CRC and matched normal tissues. Using immunochemistry, protein level of Tbx3 and EMT markers (E-cadherin and N-cadherin) were identified in 150 pairs of paraffin-embedded specimen. RESULTS: The results of qRT-PCR and western blotting showed that Tbx3 expression was higher in CRC tissues than in corresponding normal tissues. The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with tumor size (P=0.049), differentiation (P=0.032), invasion (P=0.019), lymph node metastasis (P=0.049) and TNM stage (P=0.018). Patients who displayed high expression of Tbx3 may achieve a poorer overall survival (OS) and disease-free survival (DFS), compared to those with low expression of Tbx3. This tendency was also observed in patients with intermediate levels of disease (II and III stage). The multivariate analysis indicated Tbx3 expression could independently predict the outcome of CRC patients. Interestingly, correlation analysis suggested Tbx3 expression was negatively correlated with E-cadherin expression, but positively correlated with N-cadherin expression. CONCLUSION: Tbx3 may promote CRC progression by involving EMT program and has the potential to be an effective prognostic predictor for CRC patients.

Synergistic mediation of tumor signaling pathways in hepatocellular carcinoma therapy via dual-drug-loaded pH-responsive electrospun fibrous scaffolds.

With the understanding of tumorigenesis, the tumor-infiltrating inflammatory cells, which could contribute to carcinogenesis, have greatly drawn public attention. We hypothesized that controlling inflammation in the initial stage along with antitumor activity for a relatively long term could prevent tumor recurrence. Herein, we designed a novel electrospun composite poly(l-lactide) (PLLA) fibrous scaffold, which contained sodium bicarbonate (SB) and doxorubicin (DOX) inside mesoporous silica particles (MSNs) to achieve long-term pH-sensitive DOX release and ibuprofen (IBU) outside MSNs to achieve initial short-term release. This construct was found to exhibit an initial burst release of IBU at an early stage and sustained the release of DOX at a relatively later stage. In vivo results showed that when the fibrous scaffold was implanted in a liver-tumor-bearing nude mouse, the mouse lifespan was prolonged to 1.5 times higher than that when implanted with scaffolds with no IBU or SB. Moreover, the residual tumor treated with PLLA-(MSN/DOX-SB)-IBU fibers demonstrated considerable signs of apoptosis and large areas of necrosis over a 10 week examination period. By combining the in vitro and in vivo experiments, the results have suggested that this dual drug delivery system could effectively inhibit inflammation in the initial stage and prevent tumor recurrence for a relatively long term, and it may find application as a local implantable scaffold to treat a tissue defect after tumor resection.

Novel blood-based microRNA biomarkers for diagnosis of pancreatic cancer: a meta-analysis.

BACKGROUND: Recently, several studies have shown that blood-based microRNAs in patients with pancreatic cancer (PC) could be aberrantly expressed. The purpose of this meta-analysis was to evaluate blood-based microRNAs as novel biomarkers for diagnosis of PC. METHODS: Eligible studies which had evaluated the diagnostic performance of blood-based microRNAs and had been published from February 2004 to February 2014 were retrieved. The quality of the studies was evaluated with the QUADAS-2 tool. The performance characteristics were pooled using random-effects models. Statistical analysis was performed with STATA and Meta-Disc1.4 software. RESULTS: The global meta-analysis included 12 studies from 8 articles, which contained 1,060 blood-based samples of PC patients and 935 blood-based samples of non-PC patients. Summary results suggested pooled sensitivity of 0.87 (95% confidence interval [95% CI], 0.85-0.89), specificity 0.92 (95% CI, 0.90-0.94), positive likelihood ratio 11.18 (95% CI, 5.57-22.46), negative likelihood ratio 0.16 (95% CI, 0.11-0.23), diagnostic odds ratio 88.98 (95% CI, 39.85-198.69) and the area under the summary receiver operating characteristic (SROC) curve 0.96. CONCLUSIONS: This meta-analysis demonstrated blood-based microRNA expression profiles with the potential to discriminate PC patients from non-PC patients, which have moderate diagnostic accuracy. However, further validation studies are needed for their clinical significance in the diagnosis of PC to be established.

Promotion of initial anti-tumor effect via polydopamine modified doxorubicin-loaded electrospun fibrous membranes.

Drug-loaded electrospun PLLA membranes are not conducive to adhesion between materials and tissues due to the strong hydrophobicity of PLLA, which possibly attenuate the drugs' effect loaded on the materials. In the present work, we developed a facile method to improve the hydrophilicity of doxorubicin (DOX)-loaded electrospun PLLA fibrous membranes, which could enhance the anti-tumor effect at the early stage after implantation. A mussel protein, polydopamine (PDA), could be easily grafted on the surface of hydrophobic DOX-loaded electrospun PLLA membranes (PLLA-DOX/pDA) in water solution. The morphology analysis of PLLA-DOX/pDA fibers displayed that though the fiber diameter was slightly swollen, they still maintained a 3D fibrous structure, and the XPS analysis certified that pDA had successfully been grafted onto the surface of the fibers. The results of surface wettability analysis showed that the contact angle decreased from 136.7° to 0° after grafting. In vitro MTT assay showed that the cytotoxicity of PLLA-DOX/pDA fibers was the strongest, and the stereologic cell counting assay demonstrated that the adhesiveness of PLLA/pDA fiber was significantly better than PLLA fiber. In vivo tumor-bearing mice displayed that, after one week of implantation, the tumor apoptosis and necrosis of PLLA-DOX/pDA fibers were the most obvious from histopathology and TUNEL assay. The caspase-3 activity of PLLA-DOX/pDA group was the highest using biochemical techniques, and the Bax: Bcl-2 ratio increased significantly in PLLA-DOX/pDA group through qRT-PCR analysis. All the results demonstrated that pDA can improve the affinity of the electrospun PLLA membranes and enhance the drug effect on tumors.