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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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高能聚焦超声热治疗恶性肿瘤的初步探索——附78例治疗临床应用报告

何申戌,熊六林,于晋生,兰江

《中国工程科学》 1999年 第1卷 第2期   页码 62-66

摘要：

目的 了解HIFU技术治疗癌瘤的临库效果和安全性。方法 应用FEP-BY01型高能聚焦超声肿瘤治疗机临床治疗78例中晚期腹腔、盆腔、多种脏器癌瘤，并将全部病例分为空腔脏器和实质脏器癌瘤两大类，按各自的标准进行疗效判断，并从疼痛、皮肤的灼伤、腔肠出血、穿孔及其它方面进行安全判断。结果 空腔脏器肿瘤32例，出院时65.6%肿瘤脱落消失，34.4%萎缩。实质脏器癌瘤46例；治疗后15.6%显著疗效，80.4%有效，无效4.3%（因肋骨阻挡），与放化疗合用可加速肿瘤脱落或萎缩。结论 HIFU技术对控制肿瘤有肯定疗效，并且安全可靠，值得推广应用；其相关医学基础研究须尽快开展。

关键词： 癌     热疗     体外聚焦     超声    

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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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Change and significance of T-cell subsets and TNF-α in patients with advanced malignant obstructive jaundice

ZHU Lidong, CHEN Xiaoping

《医学前沿（英文）》 2007年 第1卷 第4期   页码 364-368 doi: 10.1007/s11684-007-0070-y

摘要： The aim of this article was to study the influence of immunity function of advanced malignant obstructive jaundice (MOJ) treated by percutaneous transhepatic biliary external and internal drainage. Ninety-six cases of MOJ were divided into two groups according to the different ways of biliary drainage. Fifty-two external drainage tubes were placed in 41 cases of percutaneous transhepatic biliary external drainage group and 66 metal stents were placed in 55 cases of percutaneous transhepatic biliary internal drainage group. Liver function, serum TNF- and cellular function were examined one day before operation and one week after operation and liver function was re-examined two weeks after operation, in order to observe the change and analyze the asso ciation among them and compare with the control group. All patients conditions were improved after operation. In the percutaneous transhepatic biliary external and internal drainage groups, the total level of bilirubin decreased from (343.54±105.56) μ mol/L and (321.19±110.50) μ mol/L to (290.56±103.46) μ mol/L and (283.72±104.95) μ mol/L after operation respectively, which were significantly lower than pre-operation (<0.05), but there was no significant difference between the two groups (>0.05). Serum alanine aminotransferase (ALT) of all patients one week after operation was significantly lower than that before operation. TNF- in percutaneous transhepatic biliary external and internal groups decreased from (108.58±19.95) pg/mL, (109.98±16.24) pg/mL of pre-operation to (104.32±19.59) pg/mL, (83.92±13.43) pg/mL of post-operation respectively, there was notable improvement (<0.01) in internal drainage group after operation. Patients serum CD4, CD3 and CD4/CD8 were notably increased, but CD8 was notably decreased (<0.05). There was no difference in external drainage group (>0.05). There was a significant difference between the two groups. Serum TNF- and ALT had positive correlation. Percutaneous transhepatic biliary internal or external drainage was an effective and important method to treat MOJ. Patients immune function was weak when they suffered MOJ, but body s cellular immune function can be notably improved after internal biliary drainage.
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Pressure drop analysis on the positive half-cell of a cerium redox flow battery using computational fluid

Rivera, Berenice Miranda-Alcántara, Germán Orozco, Carlos Ponce de León, Luis F. Arenas

《化学科学与工程前沿（英文）》 2021年 第15卷 第2期   页码 399-409 doi: 10.1007/s11705-020-1934-9

摘要： Description of electrolyte fluid dynamics in the electrode compartments by mathematical models can be a powerful tool in the development of redox flow batteries (RFBs) and other electrochemical reactors. In order to determine their predictive capability, turbulent Reynolds-averaged Navier-Stokes (RANS) and free flow plus porous media (Brinkman) models were applied to compute local fluid velocities taking place in a rectangular channel electrochemical flow cell used as the positive half-cell of a cerium-based RFB for laboratory studies. Two different platinized titanium electrodes were considered, a plate plus a turbulence promoter and an expanded metal mesh. Calculated pressure drop was validated against experimental data obtained with typical cerium electrolytes. It was found that the pressure drop values were better described by the RANS approach, whereas the validity of Brinkman equations was strongly dependent on porosity and permeability values of the porous media.

关键词： CFD simulation     porous media     porous electrode     pressure drop     redox flow battery    

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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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Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 28-32 doi: 10.15302/J-FASE-2018222

摘要：

Primordial germ cells (PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by first dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells (iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established. Here, we discuss recent advances in the stem cell field for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species.

关键词： pig     pluripotent stem cells     primordial germ cells     reprogramming    

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Progress on molecular biomarkers and classification of malignant gliomas

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 150-156 doi: 10.1007/s11684-013-0267-1

摘要：

Gliomas are the most common primary intracranial tumors in adults. Anaplastic gliomas (WHO grade III) and glioblastomas (WHO grade IV) represent the major groups of malignant gliomas in the brain. Several diagnostic, predictive, and prognostic biomarkers for malignant gliomas have been reported over the last few decades, and these markers have made great contributions to the accuracy of diagnosis, therapeutic decision making, and prognosis of patients. However, heterogeneity in patient outcomes may still be observed, which highlights the insufficiency of a classification system based purely on histopathology. Great efforts have been made to incorporate new information about the molecular landscape of gliomas into novel classifications that may potentially guide treatment. In this review, we summarize three distinctive biomarkers, three most commonly altered pathways, and three classifications based on microarray data in malignant gliomas.

关键词： malignant glioma     molecular biomarker     IDH1     MGMT     molecular classification    

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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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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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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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monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 120-128 doi: 10.1007/s11684-017-0501-3

摘要：

Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) in non-neuroendocrine tumors. However, the use of 131I-MIBG is limited by its short retention time in target cells. To prolong the retention of 131I-MIBG in target cells, we infected hepatocarcinoma (HepG2) cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 (VMAT2) genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET-expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher 131I-MIBG uptake than controls. Two hours after removal of 131I-MIBG-containing medium, 25.4% efflux was observed in NET-VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer 131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after 131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2resulted in increased 131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.

关键词： norepinephrine transporter     vesicular monoamine transporter 2     -MIBG     gene therapy     lentivirus vector    

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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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标题 作者 时间 类型 操作

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

高能聚焦超声热治疗恶性肿瘤的初步探索——附78例治疗临床应用报告

何申戌,熊六林,于晋生,兰江

期刊论文

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

期刊论文

Change and significance of T-cell subsets and TNF-α in patients with advanced malignant obstructive jaundice

ZHU Lidong, CHEN Xiaoping

期刊论文

Pressure drop analysis on the positive half-cell of a cerium redox flow battery using computational fluid

Rivera, Berenice Miranda-Alcántara, Germán Orozco, Carlos Ponce de León, Luis F. Arenas

期刊论文

Rare tumors: a blue ocean of investigation

期刊论文

Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

期刊论文

Progress on molecular biomarkers and classification of malignant gliomas

null

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

Minimal residual disease in solid tumors: an overview

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

monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant

null

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