1.Bioinformatic analysis of the expression of KIF14 and its clinical significance and biological functions in clear cell renal cell carcinoma
Mengzhao ZHANG ; Yangyang YUE ; Yunzhong JIANG ; Yan LI ; Jinhai FAN
Journal of Modern Urology 2023;28(6):519-528
【Objective】 To investigate the expression of Kinesin family member 14 (KIF14), and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma (ccRCC). 【Methods】 The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA, GEO and Ualcan databases. The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method. The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER. The protein-protein interaction network of KIF14 was conducted with Genemania. The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software. The biological functions of KIF14 were verified with in vitro functional assay. 【Results】 KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage, pathological grade, and lymphatic metastasis, but negatively correlated with clinical prognosis. KIF14 expression was an independent risk factor for overall survival of ccRCC patients. GO annotations showed that KIF14 was involved in DNA replication, nuclear division, organelle fission, and cell adhesion. KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway. Genemania analysis indicated KIF14 interacted with CENPE, CIT, KIF23, and other proteins. Timer showed that KIF14 was positively correlated with immune cell infiltration. Knockdown of KIF14 expression suppressed cell proliferation, migration, and invasion of ccRCC. 【Conclusions】 KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.
2.Blocking Adenosine/A2AR Pathway for Cancer Therapy.
Jia LIU ; Yuequan SHI ; Xiaoyan LIU ; Dongming ZHANG ; Yu BAI ; Yan XU ; Mengzhao WANG
Chinese Journal of Lung Cancer 2022;25(7):460-467
Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.
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Adenosine/therapeutic use*
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Adenosine A2 Receptor Antagonists/therapeutic use*
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Humans
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Lung Neoplasms
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Receptor, Adenosine A2A/metabolism*
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Tumor Microenvironment
3.Treating non-small cell lung cancer by targeting the PI3K signaling pathway
Lin JIANG ; Jingbo ZHANG ; Yan XU ; Heng XU ; Mengzhao WANG
Chinese Medical Journal 2022;135(11):1272-1284
The phosphosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the most important intracellular signal transduction pathways affecting cell functions, such as apoptosis, translation, metabolism, and angiogenesis. Lung cancer is a malignant tumor with the highest morbidity and mortality rates in the world. It can be divided into two groups, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for >85% of all lung cancers. There are currently many clinical treatment options for NSCLC; however, traditional methods such as surgery, chemotherapy, and radiotherapy have not been able to provide patients with good survival benefits. The emergence of molecular target therapy has improved the survival and prognosis of patients with NSCLC. In recent years, there have been an increasing number of studies on NSCLC and PI3K signaling pathways. Inhibitors of various parts of the PI3K pathway have appeared in various phases of clinical trials with NSCLC as an indication. This article focuses on the role of the PI3K signaling pathway in the occurrence and development of NSCLC and summarizes the current clinical research progress and possible development strategies.
4.Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer.
Jun NI ; Miao HUANG ; Li ZHANG ; Nan WU ; Chunxue BAI ; Liang'an CHEN ; Jun LIANG ; Qian LIU ; Jie WANG ; Yilong WU ; Fengchun ZHANG ; Shuyang ZHANG ; Chun CHEN ; Jun CHEN ; Wentao FANG ; Shugeng GAO ; Jian HU ; Tao JIANG ; Shanqing LI ; Hecheng LI ; Yongde LIAO ; Yang LIU ; Deruo LIU ; Hongxu LIU ; Jianyang LIU ; Lunxu LIU ; Mengzhao WANG ; Changli WANG ; Fan YANG ; Yue YANG ; Lanjun ZHANG ; Xiuyi ZHI ; Wenzhao ZHONG ; Yuzhou GUAN ; Xiaoxiao GUO ; Chunxia HE ; Shaolei LI ; Yue LI ; Naixin LIANG ; Fangliang LU ; Chao LV ; Wei LV ; Xiaoyan SI ; Fengwei TAN ; Hanping WANG ; Jiangshan WANG ; Shi YAN ; Huaxia YANG ; Huijuan ZHU ; Junling ZHUANG ; Minglei ZHUO
Chinese Journal of Lung Cancer 2021;24(3):141-160
BACKGROUND:
Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).
METHODS:
This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.
RESULTS:
This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.
CONCLUSIONS
Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
5.COVID-19 Vaccination for Cancer Patients: Progress and Preliminary Recommendations.
Luo WANG ; Yan XU ; Lu ZHANG ; Junping FAN ; Ruili PAN ; Jinglan WANG ; Mengzhao WANG
Chinese Journal of Lung Cancer 2021;24(6):377-383
The pandemic of coronavirus disease 2019 (COVID-19) has had a serious impact on global health. COVID-19 vaccines may be one of the most effective measure to end the pandemic. High infection risk and higher serious incident and mortality rates have been shown in cancer patients with COVID-19. Therefore, cancer patients should be the priority group for COVID-19 prevention. Until now, data of COVID-19 vaccination for cancer patients is lacking. We review the interim data of safety and immune-efficacy of COVID-19 vaccination in cancer patients based on the latest studies. Due to the complicated immune systems of cancer patients caused by the malignancy and anticancer treatments, we proposed preliminary specific COVID-19 vaccination recommendations for cancer patients with different anticancer treatments and at different stages of the disease. Preventing COVID-19 with vaccinations for cancer patients is crucial, and we call for more large-scale clinical trials and real-world studies, for further COVID-19 vaccination recommendations development.
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6.Effect of Halo-Vest on dose distribution of radiotherapy for primary cervical spine malignant tumors
Xile ZHANG ; Ruijie YANG ; Na MENG ; Mengzhao LI ; Junjie WANG ; Hongqing ZHUANG ; Suqing TIAN
Chinese Journal of Radiological Medicine and Protection 2020;40(8):612-617
Objective:To investigate the effect of Halo-Vest on the dose distribution of different radiotherapy techniques for primary cervical spine malignant tumors.Methods:Ten patients with primary cervical spine malignancies who underwent radiotherapy after Halo-Vest surgery were retrospectively studied. The IMRT and VMAT plans were designed on the contoured CT images including Halo-Vest delineations using Monaco planning system. The IMRT and VMAT plans with the same field parameters were duplicated to the CT images without the Halo-Vest delineations, and the dose distribution was recalculated. The dose distribution of the target, organs at risk and normal tissues was analyzed and compared for the plans with and without the Halo-Vest delineation.Results:For most dosimetric parameters of VMAT plans, the mean deviations induced by the Halo-Vest were less than 1%, except for PGTV 107%. Without Halo-Vest delineation, the mean maximum dose of spinal cord and spinal cord-PRV increased by 0.38 Gy and 0.42 Gy ( Z=-2.803, -2.803, P<0.05), respectively. The mean Dmean of spinal cord and spinal cord PRV increased by 0.35 Gy and 0.37 Gy, respectively ( Z=-2.703, -2.701, P<0.05). The maximum deviation observed in the mean V5, V30, and Dmean of mucosa, thyroid, parotid gland, mandible, mandibular joint, and normal tissues was 0.74%. For IMRT plans, larger dosimetric deviations than VMAT plans were observed in PTV and PGTV, most of which were more than 1.0% and the maximum deviation was 4.55%. The absence of Halo-Vest delineation increased the mean maximum dose of spinal cord and spinal cord-PRV by 0.48 Gy and 0.59 Gy ( P>0.05), respectively. The mean Dmean of spinal cord and spinal cord PRV increased by 0.57 Gy and 0.59 Gy, respectively ( Z=-2.293, -2.293, P<0.05). The maximum deviation of other organs at risk was 1.98%. Conclusions:There are no clinically significant dose differences for VMAT planning with or without Halo-Vest delineation on the CT images. But the dosimetric impact of absent or partial Halo-Vest delineation on IMRT planning is relatively large and should be considered.
7.Reconsideration of indications for gallbladder-preserving cholecystolithotomy and preventive measures for postoperative recurrence of gallstones
Yanfei LI ; Qiancheng DU ; Mengzhao ZHANG
Journal of Clinical Hepatology 2019;35(3):690-695
Choledochoscopic minimally invasive gallbladder-preserving cholecystolithotomy is a surgical method for preserving the gallbladder in the treatment of gallstones, and recurrence of gallstones is a hot topic for gallbladder-preserving cholecystolithotomy. The postoperative recurrence rate of gallstones can be reduced by selecting appropriate surgical indications and adopting effective preventive measures after surgery. This article reviews the indications for minimally invasive gallbladder-preserving cholecystolithotomy and postoperative preventive measures for the recurrence of gallstones, in order to better understand the influencing factors for recurrence and provide guidance for the treatment of gallstones by minimally invasive gallbladder-preserving cholecystolithotomy.
8.Clinical Diagnosis and Treatment Recommendations for Ocular Toxicities of Target Therapy and Immune Checkpoint Inhibitor Therapy.
Xiaowei LIU ; Zheng WANG ; Chan ZHAO ; Hanping WANG ; Xiaoxiao GUO ; Jiaxin ZHOU ; Lian DUAN ; Xiaoyan SI ; Li ZHANG ; Yue LI ; Mengzhao WANG ; Juhong SHI ; Meifen ZHANG ; Li ZHANG
Chinese Journal of Lung Cancer 2019;22(10):653-660
The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.
9.Clinical Diagnosis and Treatment Recommendations for the Pneumonitis Associated with Immune Checkpoint Inhibitor.
Hanping WANG ; Xiaoxiao GUO ; Jiaxin ZHOU ; Lian DUAN ; Xiaoyan SI ; Li ZHANG ; Yue LI ; Xiaowei LIU ; Mengzhao WANG ; Juhong SHI ; Li ZHANG
Chinese Journal of Lung Cancer 2019;22(10):621-626
The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.
10.Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors.
Hanping WANG ; Peng SONG ; Xiaoyan SI ; Xiaoxiao GUO ; Yue LI ; Jiaxin ZHOU ; Lian DUAN ; Li ZHANG ; Mengzhao WANG ; Li ZHANG
Chinese Journal of Lung Cancer 2019;22(10):605-614
The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

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