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Minimal residual disease in solid tumors: an overview

《医学前沿（英文）》 2023年 第17卷 第4期   页码 649-674 doi: 10.1007/s11684-023-1018-6

摘要： Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment.

关键词： MRD     solid tumor     CTC     ctDNA    

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Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

《化学科学与工程前沿（英文）》 2022年 第16卷 第3期   页码 333-344 doi: 10.1007/s11705-021-2059-5

摘要： Compared to conventional hyperthermia that is limited by low selectivity and severe side effects, nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment. Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia, which introduces a new avenue, allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery, i.e., long-lasting and/or systemic anti-tumor immunity. This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia. This includes the discussion about underlying mechanism such as immunogenic cell death, which initiates a profound immunological chain reaction. In order to propagate the immune activation as a viable therapeutic principle, we further discussed the tumor type-specific complexity in the immunological tumor microenvironment, including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.

关键词： nano-enabled hyperthermia     immunogenic cell death     heterogeneous immunological landscape     tumor microenvironment    

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Rare tumors: a blue ocean of investigation

《医学前沿（英文）》 2023年 第17卷 第2期   页码 220-230 doi: 10.1007/s11684-023-0984-z

摘要： Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients’ prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

关键词： rare tumors     diagnosis flowchart     treatment strategy     clinical trials recommendation    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?

《医学前沿（英文）》 2022年 第16卷 第3期   页码 322-338 doi: 10.1007/s11684-021-0901-2

摘要： Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

《医学前沿（英文）》   页码 805-822 doi: 10.1007/s11684-023-1025-7

摘要： Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

关键词： CTLA-4     PD-1     PD-L1     immune checkpoint blockade (ICB)     metabolic reprogramming     combined tumor therapeutic strategies    

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Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely

Bin Yang, Yan Yu, Jing Chen, Yan Zhang, Ye Yin, Nan Yu, Ge Chen, Shifei Zhu, Haiyan Huang, Yongqun Yuan, Jihui Ai, Xinyu Wang, Kezhen Li

《医学前沿（英文）》 2018年 第12卷 第5期   页码 509-517 doi: 10.1007/s11684-017-0554-3

摘要：

This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P=0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P<0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.

关键词： malignant germ cell tumors     ovarian sex cord-stromal tumors     fertility-sparing surgery     prognosis     fertility    

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Molecular targeted therapy of gynecological malignant tumors: the development and challenge, from laboratory

Pengming SUN PhD, MD , Jalid SEHOULI PhD, MD , Lihui WEI BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 256-264 doi: 10.1007/s11684-009-0052-3

摘要： More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer, especially in ovarian cancer. In this article, we systematically review the current targeted therapeutic trials running in clinic. Large, randomized trials have been conducted in the treatment of ovarian cancer, endometrial cancer and cervical cancer by using small molecule, antisense, mutational gene as well as antibodies. Other planned or ongoing trials currentlytargeted at molecular markers which may play important roles in gynecological carcinogenesis andprogression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an importantoption.

关键词： target therapy     gynecologic malignant tumors     clinical trail     molecular medicine    

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High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

《医学前沿（英文）》   页码 907-923 doi: 10.1007/s11684-023-1009-7

摘要： The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

关键词： FAK6/7     SRRM4     neuroendocrine neoplasms     pancreas     breast    

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Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumors: a study of

LIANG Yumei, LI Xianghong, LU Youyong, LV Yali, ZHONG Mei, PU Xiaolu, LI Wenmei

《医学前沿（英文）》 2008年 第2卷 第1期   页码 87-94 doi: 10.1007/s11684-008-0016-z

摘要： The biological behavior of gastrointestinal stromal tumors (GISTs) are highly variable. To investigate the biological behavior of GIST, we collected 83 cases of gastric and 62 cases of small intestinal GIST from the Department of Pathology of the Chinese PLA General Hospital. The parameters include age, primary tumor location, tumor diameter, mitotic index, tumor necrosis, risk assessment, clinical stage and the exon 11 mutation. All these were analyzed in 105 cases along with the follow-up data and tested by log rank and COX hazard proportional model. We find that the average age of gastric GIST was 55.4 years. Of the 62 cases that were followed up, 17 cases had metastasis or recurrence and the 5-year survival rate was (66.51 ± 17.06)%. For the small intestinal GIST, the average age was 50.6 years and 43 cases were followed up. Of these, 22 cases had metastasis or recurrence and the 5-year survival rate was (61.76 ± 18.30)%. Small intestinal GIST was more frequently associated with metastasis and tumor relapse than gastric GIST ( = 6.131, = 0.013). For gastric GIST, patients younger than 50 years ( = 0.046), the advanced clinical stage ( = 0.0001), the large tumor diameter ( = 0.0001), a high mitotic index ( = 0.0001), necrosis ( = 0.0001) and a high risk grade ( = 0.004) were all correlated with a lower survival rate. The COX hazard proportional model revealed that advanced clinical stage ( = 0.001), large tumor size ( = 0.001), a high mitotic index ( = 0.002) and the high risk grade ( = 0.018) indicated a poorer prognosis in gastric GIST. For small intestinal GIST, necrosis ( = 0.036) and advanced clinical stage ( = 0.010) were associated with lower survival rates and the clinical stage was shown to be an independent prognostic indicator. A total of 25 cases harbored mutations in exon 11. The frequency of mutation was 32% and 22.5% for gastric and small intestinal GIST, respectively. In gastric GIST, the mutated was predominant in patients older than 50 years of age. But in the small intestinal GIST, the mutated was predominant in the age group of 40–49 years. In conclusion, for gastric GIST, clinical stage, tumor size, mitotic index, and risk grade are the prognostic indicators. For small intestinal GIST, necrosis and clinical stage are the prognostic indicators. Small intestinal GIST are more aggressive than gastric GIST. The occurrence of mutation may correlate with the age of patients.
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Potential indicators predict progress after surgical resection of gastrointestinal stromal tumors

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 317-321 doi: 10.1007/s11684-012-0203-9

摘要：

In order to find out the potential indicators predicting prognosis of malignant gastrointestinal stromal tumors (GISTs) after surgical resection, we collected clinical records of 80 patients with malignant GISTs. Tumor location, size, mitotic index, necrosis were compared with the prognosis of malignant GISTs by Kaplan-Meier method and log-rank test. After a median follow-up of 844 days (52–2 145), we found that as National Institutes of Health suggested, tumors with intermediate risk had more favorable prognosis than that with high risk. Their 3-year survival rate were 65.3% and 41.3%, respectively (P<0.001). Moreover, tumor size and mitotic index were associated with free survival. The 3-year survival rate for patients with tumor size≤10 cm and>10 cm were 62.3% and 41.8%, respectively (P = 0.002), Tumors with mitotic index≤5/50 HPF had a higher 3-year survival rate than tumors with mitotic index>5/50 HPF (67.1% versus 40.7%, P = 0.005). The presence of necrosis was directly related to the malignant behavior. The 3-year survival rate for presence and absence necrosis were 50.8% and 64.8% (P = 0.008). From the present study, we can conclude that besides tumors size and mitotic index, tumor location and necrosis also influence on the long-term survival of patient with malignant GISTs after surgical resection.

关键词： gastrointestinal stromal tumors     surgery     survival    

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Retrospective study of the efficacy and complication of thoracoabdominal incision for nephrectomy: a comparison with flank approach

Minggen YANG, Xiaokun ZHAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 191-196 doi: 10.1007/s11684-009-0026-5

摘要： This retrospective study was performed to compare the outcome of thoracoabdominal incision flank incision for radical nephrectomy in the patients with large renal tumors. A questionnaire assessing postoperative pain, administration of pain medications and the return to activities and work was sent to the patients who undergoing radical nephrectomy through the 11th rib (group 1: underwent flank incision, including 96 patients) or the 9th to 10th rib (group 2: undergoing thoracoabdominal incision, including 98 patients) from 2003 to 2007 in our hospital. A case retrospective analysis assessing operation time, perioperative hemorrhage volume, size of tumor, success in the treatment of tumor thrombus in renal vein or vena cava, time length of presence of drainage tube, postoperative analgesia usage and length of stay was conducted in patients whose questionnaires were returned. A total of 56 patients (58%) in group 1 and 60 (61%) in group 2 responded to the questionnaire. Time lengths of operation and presence of abdominal drainage tube were shorter in group 2 than those in group 1. Perioperative hemorrhage volume in group 2 was obviously less than that in group 1. The mean size of tumors in group 1 was significantly smaller than that in group 2 ( < 0.0005). The success rate of treating thrombus in renal vein or vena cava in group 2 was significantly higher than that in group 1 ( <0.05). Lengths of off-bed time and stay were the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge and 1 month postoperatively ( >0.05). There were no significant differences between groups in the time following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work ( >0.05). The thoracoabdominal incision provides excellent exposure and allows for early vascular control. Efficacy and complication was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge and return to normal activities.

关键词： surgery     renal tumors     nephrectomy    

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Plasma spray coating on interconnector toward promoted solid oxide fuel cells and solid oxide electrolysis

《能源前沿（英文）》 doi: 10.1007/s11708-023-0901-9

摘要： Interconnector is a critical component to construct solid oxide cells (SOCs) stack. Oxidation of metallic interconnectors and Cr poisoning caused by oxidation are important factors that lead to long-term performance degradation of SOCs. Coating on the interconnector surface is an important approach to inhibit the oxidation and Cr migration of the interconnector. Herein, (La0.75Sr0.25)0.95MnO3–δ (LSM) and Mn1.5Co1.5O4 (MCO) are used to fabricate the coatings of interconnector. Two advanced thermal spray technology, atmospheric plasma spraying (APS) and low-pressure plasma spray (LPPS), are adopted for the coating preparation. The electrochemical performance, rising and cooling cycle stability, and Cr diffusion inhibition performance of the coatings are tested and evaluated. The result indicates that MCO can generate more uniform and denser coatings than LSM. In addition, MCO coatings prepared by LPPS shows the best electrochemical performance, rising and cooling cycle stability, and Cr diffusion inhibition. The initial area specific resistance (ASR) is 0.0027 Ω·cm2 at 800 °C. After 4 cooling cycle tests, the ASR increases to 0.0032 Ω·cm2 but lower than other samples. Meanwhile, the relative intense of Cr at the interface of SUS430 with MCO coatings fabricated by LPPS is lower than that of MCO fabricated by APS after 4 rising and cooling cycle operations, showing more favorable Cr diffusion inhibition performance.

关键词： interconnector coating     plasma spray     electrochemical performance     Cr diffusion inhibition     solid oxide cells (SOCs)    

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High-solid anaerobic digestion of sewage sludge: achievements and perspectives

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1364-4

摘要：

• High-solid anaerobic digestion (HS-AD) of sewage sludge (SS) is overviewed.

关键词： High-solid effect     Anaerobic fermentation     Methane production     Biodegradability     Sludge treatment    

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Review of SO42-/MxOy solid superacid catalysts

Yanni WU, Shijun LIAO

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 330-343 doi: 10.1007/s11705-009-0208-3

摘要： Some metal oxides modified with sulfate ions form highly acidic or superacidic catalysts. solid superacid catalysts, play a vital role in more and more fields such as organic synthesis, fine chemicals, pharmaceuticals, and means for strengthening environmental safeguards. This review highlights the recent development of solid superacid catalysts based on , including synthesis method, characterization of acid sites and acid strength, and applications.

关键词： solid superacid catalyst     synthesis method     characterization     applications    

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Repercussions of COVID-19 pandemic on solid waste generation and management strategies

《环境科学与工程前沿（英文）》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1407-5

摘要：

• Implication of COVID-19 on medical waste and MSW generation is studied.

关键词： COVID-19     Medical waste     Personal protective equipment     Municipal solid waste     Waste management    

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标题 作者 时间 类型 操作

Minimal residual disease in solid tumors: an overview

期刊论文

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

期刊论文

Rare tumors: a blue ocean of investigation

期刊论文

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?

期刊论文

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

期刊论文

Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely

Bin Yang, Yan Yu, Jing Chen, Yan Zhang, Ye Yin, Nan Yu, Ge Chen, Shifei Zhu, Haiyan Huang, Yongqun Yuan, Jihui Ai, Xinyu Wang, Kezhen Li

期刊论文

Molecular targeted therapy of gynecological malignant tumors: the development and challenge, from laboratory

Pengming SUN PhD, MD , Jalid SEHOULI PhD, MD , Lihui WEI BM ,

期刊论文

High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

期刊论文

Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumors: a study of

LIANG Yumei, LI Xianghong, LU Youyong, LV Yali, ZHONG Mei, PU Xiaolu, LI Wenmei

期刊论文

Potential indicators predict progress after surgical resection of gastrointestinal stromal tumors

null

期刊论文

Retrospective study of the efficacy and complication of thoracoabdominal incision for nephrectomy: a comparison with flank approach

Minggen YANG, Xiaokun ZHAO

期刊论文

Plasma spray coating on interconnector toward promoted solid oxide fuel cells and solid oxide electrolysis

期刊论文

High-solid anaerobic digestion of sewage sludge: achievements and perspectives

期刊论文

Review of SO42-/MxOy solid superacid catalysts

Yanni WU, Shijun LIAO

期刊论文

Repercussions of COVID-19 pandemic on solid waste generation and management strategies

期刊论文