The crosstalk between SUMOylation and immune system in host-pathogen interactions.

Pathogens can not only cause infectious diseases, immune system diseases, and chronic diseases, but also serve as potential triggers or initiators for certain tumors. They directly or indirectly damage human health and are one of the leading causes of global deaths. Small ubiquitin-like modifier (SUMO) modification, a type of protein post-translational modification (PTM) that occurs when SUMO groups bond covalently to particular lysine residues on substrate proteins, plays a crucial role in both innate and adaptive immunologic responses, as well as pathogen-host immune system crosstalk. SUMOylation participates in the host's defense against pathogens by regulating immune responses, while numerically vast and taxonomically diverse pathogens have evolved to exploit the cellular SUMO modification system to break through innate defenses. Here, we describe the characteristics and multiple functions of SUMOylation as a pivotal PTM mechanism, the tactics employed by various pathogens to counteract the immune system through targeting host SUMOylation, and the character of the SUMOylation system in the fight between pathogens and the host immune system. We have also included a summary of the potential anti-pathogen SUMO enzyme inhibitors. This review serves as a reference for basic research and clinical practice in the diagnosis, prognosis, and treatment of pathogenic microorganism-caused disorders.

An ultrasound-based nomogram for predicting axillary node pathologic complete response after neoadjuvant chemotherapy in breast cancer: Modeling and external validation.

INTRODUCTION: The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. METHODS: Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. RESULTS: This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. CONCLUSIONS: A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.

CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Impact of Sentinel Lymph Node Biopsy on Treatment Decision and Survival in Patients Aged ≥70 Years with Breast Cancer: A Retrospective Study.

Background: Whether sentinel lymph node biopsy should be performed in patients ≥70 years old with early-stage invasive breast cancer is controversial. We examined the effect of sentinel lymph node biopsy on the treatment and outcomes in this population. Materials and Methods: In this retrospective study, patients aged ≥70 years who were treated for invasive breast cancer with sentinel lymph node biopsy followed by mastectomy or lumpectomy between 2010 and 2019 were identified from our database. Patients were compared according to sentinel lymph node status. Outcomes were analyzed using the Kaplan-Meier method and Cox multivariate analysis. Results: Of the 376 patients enrolled in this study, 311 (82.7%) were sentinel lymph node-negative and 65 (17.3%) were sentinel lymph node-positive. The median follow-up duration for all patients was 70 months. Systemic treatment and radiation were similar between sentinel lymph node-negative and -positive groups. Disease-free survival, distant disease-free survival, breast cancer-specific survival, overall survival were not significantly different between groups (88.2% vs 87.6%, 96.7% vs 94.8%, 96.2% vs 93.6%, and 93.5% vs 90.0%, respectively). Sentinel lymph node status, tumor size, chemotherapy, endocrine therapy, and adjuvant radiation were included in Cox multivariate analysis. None of the variables were found to significantly affect disease-free survival, distant disease-free survival, breast cancer-specific survival, and overall survival. Conclusions: Our analysis indicated that sentinel lymph node status may not affect systemic treatment decisions or survival in patients aged ≥70 years with breast cancer.

Effect of Local Versus General Anesthesia in Breast-Conserving Surgery on Cancer Recurrence and Cost.

BACKGROUND: The association between the type of anesthesia used and the recurrence of cancer remains controversial. This study aimed to compare the effects of local vs general anesthesia on recurrence-free survival and cost after breast-conserving surgery. MATERIALS AND METHODS: We reviewed the data of 2778 patients who underwent breast-conserving surgery followed by radiation at our center between 1999 and 2014. We analyzed the data of 994 patients with hormone receptor-positive and Her2-negative tumors who underwent breast-conserving surgery without axillary lymph node dissection under local or general anesthesia. Patients were grouped according to whether local or general anesthesia was used for the surgery. RESULTS: Of the 994 patients enrolled in this study, 367 received local anesthesia and 627 patients received general anesthesia. The median follow-up duration for all patients was 93 months. The Kaplan-Meier survival curves did not reveal significant differences between the recurrence-free survival of the two groups, with 5-year recurrence-free survival rates of 96.3% (95% CI, 94.3-98.3%) in the local anesthesia group and 97.3% (95% CI, 95.9-98.7%) in the general anesthesia group. The total cost of hospitalization in the local anesthesia group was significantly lower than that in the general anesthesia group (P <.001). The difference in the cost between the two groups remained significant, irrespective of the type of hospitalization, after excluding 165 patients receiving chemotherapy during their hospitalization. CONCLUSIONS: Our analysis indicated no association between the type of anesthesia used during breast-conserving surgery and the long-term prognosis of breast cancer. However, breast-conserving surgery under local anesthesia may be a less expensive option than that under general anesthesia.

Impact of dose-dense neoadjuvant chemotherapy on pathologic response and survival for HER2-positive breast cancer patients who receive trastuzumab.

To compare outcomes in patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer who received either dose-dense neoadjuvant chemotherapy (NAC) with trastuzumab or standard-interval chemotherapy with trastuzumab. Patients with HER2-positive breast cancer who received NAC, including epirubicin and cyclophosphamide followed by paclitaxel with trastuzumab were included. Patients were divided into either the dose-dense or standard-interval group. We compared pathologic complete remission (pCR), distant disease-free survival (DDFS), event-free survival (EFS), and breast cancer-specific survival (BCSS) between the two groups. Two hundred (49.6%) patients received dose-dense NAC, and 203 (50.4%) received standard-interval NAC. The pCR rate was 38.4% in the dose-dense group and 29.2% in the standard-interval group (P = 0.052). In patients with lymph node (LN) metastases, the LN pCR rate was 70.9% in the dose-dense group and 56.5% in the standard-interval group (P = 0.037). After a median follow-up of 54.6 months, dose-dense chemotherapy presented an improvement on DDFS (hazard ratio [HR] = 0.49, 95% confidence interval [CI]: 0.19-1.28, EFS (HR = 0.54, 95% CI: 0.24-1.21), and BCSS (HR = 0.41, 95% CI: 0.11-1.51), but the difference was not significant. Compared with standard-interval chemotherapy, dose-dense chemotherapy resulted in a superior 5-year DDFS (100% vs. 75.3%, P = 0.017) and 5-year EFS (96.9% vs. 78.3%, P = 0.022) in patients younger than 40 years. HER2-positive patients can achieve a higher LN pCR rate with dose-dense NAC than with standard-interval NAC with trastuzumab. Better survival may also be achieved with dose-dense chemotherapy with trastuzumab than with standard-interval chemotherapy with trastuzumab among young patients (age ≤ 40 years).

Comparisons of breast conserving therapy versus mastectomy in young and old women with early-stage breast cancer: long-term results using propensity score adjustment method.

PURPOSE: This study aimed to compare the effect of BCT versus mastectomy on the recurrence and survival of different-aged patients, and to investigate whether effects of BCT versus mastectomy on survival of young patients were consistent with those of old patients. METHODS: Data on women with primary invasive breast cancer between 2007 and 2011 were extracted from the institutional database of Breast Center. Disparities in hormone receptor, tumor size, lymph node status, and Her-2 status between BCT and mastectomy groups were adjusted using the propensity score (PS) adjustment method. Patients were divided by age into two groups (≤ 40 years and > 40 years). We assessed proportions of local recurrence (LR), distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in different-aged groups; this assessment was further stratified by surgical treatment. RESULTS: A total of 2964 patients were included; 565 (19%) were aged ≤ 40 years. In the entire cohort, hazard ratios (HR) of BCT versus mastectomy for DDFS and DFS were 0.56 (P = 0.029) and 0.55 (P = 0.008), respectively. After PS adjustment, there was no significant difference between BCT and mastectomy in LR, DDFS, DFS and BCSS in the young age group. In the old age group, women who underwent BCT exhibited improved DDFS (HR 0.57, 95% CI 0.39-0.84, P = 0.004). CONCLUSIONS: BCT did not significantly affect survival outcomes of young patients with breast cancer. Superior survival of BCT compared to mastectomy was observed only in old patients.

Impact of clinical and pathological factors on local recurrence after breast-conserving treatment: CT-based localization for a tumor bed boost yielded better local control when compared with a surgical scar.

Background: We investigated the effects of risk factors on the incidence of local recurrence (LR) in patients who underwent breast-conserving treatment (BCT) for primary breast cancer at a single institution in China from 1999 to 2011. Methods: Patient outcomes were compared with respect to LR, ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and disease-free survival (DFS). Additionally, the risk factors for relapse after BCT were studied. Results: The 2028 patients with invasive breast cancer included in this study were followed for a median of 95 months, during which the 8-year LR, IBTR, DDFS, and DFS rates were 2.6%, 3.0%, 93.7%, and 91.3%, respectively. Lymph node involvement, the human epidermal growth factor receptor 2 (HER2) status, and the use of computed tomography (CT) information during boost field planning were identified as significant predictors of LR and IBTR. Notably, use of the surgical scar for tumor bed identification during boost field planning was associated with a higher adjusted risk of LR, compared with the use of CT. By contrast, the neoadjuvant chemotherapy (NAC) was not an independent predictor of LR (hazard ratio of no NAC vs. NAC, 0.63; 95% confidence interval, 0.33-1.19; P = 0.157). In a multivariate analysis, the age at diagnosis, tumor diameter, lymph node involvement, HER2-positive status, and use of CT information during boost field planning were identified as significant factors affecting DFS. Conclusions: The use of CT information during boost field planning could reduce the risk of LR among patients undergoing BCT. Neoadjuvant and adjuvant treatments for breast cancer did not show the significant difference in respect to the outcome of LR.

Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma: a matched comparative study.

BACKGROUND: To compare two types of therapy for primary breast carcinoma, breast-conserving therapy (BCT) and modified radical mastectomy (MRM), in a matched cohort study. METHODS: A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence (LR), distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1:1, and each arm included 873 patients. RESULTS: The median follow-up period was 71 months. The 6-year disease-free survival (DFS) and 6-year distant disease-free survival (DDFS) rates differed significantly between two groups. The 6-year local recurrence-free survival (LRFS) rates were 98.2% [95% confidence interval (CI): 0.973-0.989] in the BCT group and 98.7% (95% CI: 0.980-0.994) in the MRM group (P=0.182), respectively. DFS rates in BCT and MRM groups were 91.3% (95% CI: 0.894-0.932) and 86.3% (95% CI: 0.840-0.886) (P<0.001), respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% (95% CI: 0.922-0.950) and 87.7% (95% CI: 0.854-0.900) (P<0.001), respectively. CONCLUSIONS: BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.

[Safety of breast-conserving treatment for triple-negative breast cancer].

OBJECTIVE: To investigate the effect of risk factors on ipsilateral breast tumor recurrence (IBTR) and distant disease-free survival (DDFS) for patients with triple-negative breast cancer (TNBC) who underwent breast-conserving treatment (BCT). METHODS: A series of 1 835 patients with primary breast cancer treated with BCT in a single institute between December 1999 and August 2010 were analyzed retrospectively. Totally 1 614 patients, whose characteristics were intact, were analyzed to compare their outcomes with respect to the incidence of IBTR, DDFS and disease-free survival (DFS). All of patients were female. Median age was 47 years (ranging 21 to 92 years, interquartile range 14 years). According to the immunohistochemical results of the patients, 1 614 cases were divided into TNBC group (n=308) and non-TNBC group (n=1 306). The risk factors of relapse after breast-conserving treatment (age at diagnosis, spread to axillary lymph nodes, hormone receptor status, neoadjuvant chemotherapy, and maximal tumor diameter, human epidermal growth factor receptor 2 (HER-2) status, preoperative MRI, the location and extent of the tumor bed defined by CT scans for electron boost planning as part of breast radiotherapy) were studied.χ(2) test was used to compare the distribution of baseline characteristics among subtypes. The probability of survival (or relapse occurrence), and DDFS were calculated using the Kaplan-Meier method. Cumulative incidence functions were used to describe the cumulative hazard from LR, IBTR and DDFS in the presence of competing risks. RESULTS: A total of 1 614 women with primary breast cancer underwent a breast-conserving surgery followed by radiotherapy. The median follow-up period was 77 months (interquartile range 36 months). One hundred and forty patients (8.6%) were lost to follow-up. Overall 5-year IBTR rate was 3.1% (95% CI: 2.2% to 4.0%), 5-year DDFS rate was 95.8% (95% CI: 94.9% to 96.7%) and 5-year DFS rate was 93.8% (95% CI: 92.7% to 94.9%). Lymph nodal involvement (HR=3.03, 95% CI: 1.66 to 5.51, P=0.000) and use of CT information in boost field planning (HR=0.40, 95% CI: 0.20 to 0.80, P=0.010) were associated significantly with IBTR in Cox multivariable analysis. Multivariable analysis showed that TNBC doesn't have a significantly increased risk of IBTR compared with the non-TNBC subtype (HR=0.90, 95% CI: 0.50 to 1.76, P=0.78). TNBC was not an independent risk factor for DDFS or DFS. The multivariable model showed significant effect of nodal status and age at diagnosis on 5-year DDFS rate and 5-year DFS rate. CONCLUSIONS: Breast-conserving treatment for TNBC is not associated with increased IBTR compared with non-TNBC subtype. Use of CT information in boost field planning can reduce the risk of ipsilateral breast tumor recurrence for patients undergoing BCT.

[Survival analysis for different molecular subtypes of breast cancers after treatment].

OBJECTIVE: To explore the survival status after treatment for patients with different molecular subtypes of breast cancers. METHODS: A total of 4491 patients with invasive breast cancer from January 2000 to July 2011 were retrospectively recruited to receive pathological verification and treatment at our clinic. According to the immunohistochemical results of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), they were assigned into 3 groups of HR+/HER2-, HER2+ and HR-/ HER2-. Survival analyses were conducted to examine the effects of molecular subtypes and lymph node status on survival. RESULTS: The 3-year recurrence free survival for HR+/HER2-, HER2+ and HR-/HER2- were 94.9%, 89.5% ane 92.3% respectively. Different molecular subtypes presented different survival patterns (P = 0.0001). The 3-year recurrence-free survival (RFS) for LN+ and LN- was 87.1% and 97.8% respectively. And statistical difference existed (P < 0.01). No difference was detected among three molecular subtypes of LN- (P = 0.102); However, for LN+ patients, HR+/HER2- showed a higher RFS than HER2+ and HR-/HER2 (P = 0.001). CONCLUSION: Different molecular subtypes of breast cancers have varying survival. And lymph node status is probably an important prognostic factor.

[Efficacy analysis of THP-containing regimens as neoadjuvant and adjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer. METHODS: Two hundred and eighty-nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed. RESULTS: The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047). CONCLUSIONS: CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen.

[The clinical research of local recurrence after breast-conserving therapy for breast cancer].

OBJECTIVE: To compare and analyze the data of breast cancer recurrence after breast-conserving therapy (BCT), and to find high risk factors that can affect local recurrence. METHODS: A total of 1034 patients in the data base between January 2000 and June 2008 were analyzed retrospectively. The patients aged 23 to 94 years when diagnosed (median age, 48 years). The data was investigated to compare of two different groups in local recurrence rate and survival rate. The high risk factors of recurrence after BCT [estrogen receptor (ER)/progesterone receptor (PR), human epidermal growth factor receptor (HER-2), age, lymph node involvement, tumor diameter, neoadjuvant chemotherapy, pathological status] were studied. RESULTS: The patients were followed-up to June 2010, and the median period was 42 months (range, 3-126 months). During the period, 35 patients developed ipsilateral breast tumor recurrence (3.3%), 47 patients had metastasis to distant organs (4.5%). The 5-year disease-free survival was 87.7%, 5-year distant disease-free survival was 94.0%. The lymph node status, HER-2 status and age were significant risk factors for ipsilateral breast tumor recurrence on univariate analysis. One peak recurrence period was from the 2nd to 3rd year, and the other was from the 5th to 6th year after the operation. The HER-2 status was independent factors of ipsilateral breast tumor recurrence on multivariate analysis. CONCLUSIONS: The recurrence happens primarily in the 2nd to 3rd and the 5th to 6th year after the breast-conserving therapy. HER-2 status is an independent factor of ipsilateral breast tumor recurrence. The patients with high risk factors of recurrence should be treated more aggressively.

Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation.

The aim of this study was to determine whether the number of passages affected the developmental pluripotency of embryonic stem (ES) cells as measured by the attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid embryo complementation. Thirty-six newborns were produced by the aggregation of tetraploid embryos and hybrid ES cells after various numbers of passages. These newborns were entirely derived from ES cells as judged by microsatellite DNA, coat-color phenotype, and germline transmission. Although 15 survived to adulthood, 17 died of respiratory failure, and four were eaten by their foster mother. From the 15 mice that reached adulthood and that could reproduce, none arose from ES cells at passage level 15 or more. All 15 arose from cells at passages 3-11. Our results demonstrate that the number of passages affects the developmental pluripotency of ES cells.

[Study on mtDNA D-loop of Chinese main indigenous sheep breeds using PCR-RFLP].

The polymorphism of mtDNA D-loop of 83 individuals from 9 Chinese indigenous sheep breeds and 2 imported sheep breeds were studied with 5 endonucleases, Hinf I, Msp I, Sau3A I, Xsp I and Taq I, using PCR-RFLP. The results indicated that there existed two basic haplotypes in the region of mtDNA D-loop. It could be inferred that Chinese indigenous sheep breeds originated from two maternal ancestors. The averaged polymorphic degree (Pi value=0.0421%) of mtDNA D-loop showed that the genetic diversity of mtDNA of Chinese indigenous sheep breeds was very poor.