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PD-1/PD-L1 Signaling Pathway and Tumor Immune Escape

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Journal of Biosciences and Medicines 2023年第3期11卷 9-16页

作者： Zhenqi Xu Wei Du department of oncology The First Affiliated Hospital of Yangtze University Jingzhou China

PD-1 and its ligands PD-L1 and PD-L2 are widely expressed on the surface of a variety of cells and are a group of costimulatory molecules related to negative immune regulation. The activation of the PD-1/PD-L1 signaling pathway is beneficial for tumors to escape from immune surveillance, but the specific tumor immune escape mechanism is not yet clear. As far as the efficacy of anti-PD-1 and anti-PD-L1 antibodies is concerned, more in-depth research on tumor immune escape mechanisms is still needed. The article summarizes these findings to provide ideas for antitumor immunotherapy.

关键词： Programmed Death 1 Programmed Death Ligand 1 Neoplasms Immunotherapy

Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

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World Journal of Clinical oncology 2024年第4期15卷 472-477页

作者： Sigfredo E Romero-Zoghbi Fernando López-Campos Felipe Couñago department of Radiation oncology GenesisCareTalavera de la Reina 45600ToledoSpain department of Radiation oncology Hospital Universitario Ramón Y CajalMadrid 28034Spain department of Radiation oncology GenesisCare-Hospital Universitario Vithas Madrid La MilagrosaMadrid 28010Spain

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal *** treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent *** dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern *** contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal *** the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient *** the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

关键词： Rectal cancer Lateral pelvic lymph node metastases Pelvic lymph node dissection Total neoadjuvant therapy Selective management of the lateral pelvic nodes Prophylactic management of the lateral pelvic nodes Chemoradiotherapy Total mesorectal excision

Cancer/testis antigens： novel tools for discerning aggressive and non-aggressive prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 400-404,I0006页

作者： Takumi Shiraishi Robert H Getzenberg Prakash Kulkarni department of Urology James Buchanan Brady Urological Institute Baltimore M D 21287 USA department of Urology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan department of oncology James Buchanan Brady Urological Institute Baltimore MD 21287 USA pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine Baltimore MD 21287 USA

The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.

关键词： cancer/testis antigens DNA microarrays prostate cancer prostate carcinoma tumor antigen

Expression of thymidylate synthase and glutathione-stransferase π in patients with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2009年第34期15卷 4316-4321页

作者： Jun-Xing Huang Feng-Yue Li Wei Xiao Zheng-Xiang Song Rong-Yu Qian Ping Chen, Eeva Salminen department of Ontology The People's Hospital of Taizhou Taizhou Medical School Yangzhou & Nantong University Taizhou 225300 Jiangsu Province China department of Pathology The People's Hospital of Taizhou Taizhou Medical School Yangzhou & Nantong University Taizhou 225300 Jiangsu Province China department of oncology University of Turku & Turku University Hospital PO Box 52 20521 Turku Finland

AIM： To investigate the expression of thymidylate synthase （TS） and glutathione-s-transferase π （GST-π） in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS： Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma （ESCC） tissue sections from 102 patients （median age, 58 years） and in 28 normal esophageal mucosa （NEM） samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS： The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples （P 〈 0.05）. The expression level of TS was not only significantly lower in well-differentiated （21.88%） than in poorly-differentiated carcinomas （51.43%, P 〈 0.05）, but was also significantly higher in samples from male patients （46.51%） than from female patients （18.75%, P 〈 0.05）. GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples （P 〈 0.05）. The expression level of GST-π was also significantly higher in welldifferentiated carcinomas （65.63%） than in poorly- differentiated carcinomas （35.00%, P 〈 0.05）. CONCLUSION： The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of T5 and reduced expression of GST-π.

关键词： Esophageal squamous cell carcinoma Glutathione-s-transferase π Immunohistochemistry Thymidylate synthase Tumor markers

Measurement of copy number variation in single cancer cells using rapid-emulsification digital droplet MDA

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Microsystems & Nanoengineering 2017年第1期3卷 260-266页

作者： Samuel C.Kim Gayatri Premasekharan Iain C.Clark Hawi B.Gemeda Pamela L.Paris Adam R.Abate department of Bioengineering and Therapeutic Sciences University of CaliforniaSan Francisco(UCSF)California Institute for Quantitative Biosciences(QB3)San FranciscoSan FranciscoCA 94158USA department of Urology Division of Hematology&OncologyUniversity of CaliforniaSan Francisco(UCSF)San FranciscoCA 94158USA

Uniform amplification of low-input DNA is important for applications across biology,including single-cell genomics,forensic science,and microbial and viral ***,the requisite biochemical amplification methods are prone to bias,skewing sequence proportions and obscuring signals relating to copy *** droplet multiple displacement amplification enables uniform amplification but requires expert knowledge of microfluidics to generate monodisperse *** addition,existing microfluidic methods are tedious and labor intensive for preparing many ***,we introduce rapid-emulsification multiple displacement amplification,a method to generate monodisperse droplets with a hand-held syringe and hierarchical droplet *** conventional microfluidic devices require >10 min to emulsify a sample,our system requires tens of seconds and yields data of equivalent *** demonstrate the approach by using it to accurately measure copy number variation(CNV)in single cancer cells.

关键词： amplification bias copy number variation ddMDA droplet microfluidics multiple displacement amplification

Polyphyllin Ⅰ: A new potential antitumor agent from Rhizoma Paridis

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Polyphyllin Ⅰ: A new potential antitumor agent from Rhizoma...

Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

第十七届全国中西医结合肿瘤学术大会

作者： Jian Tang Chien-Shan Cheng Lian-Yu Chen Zhen Chen department of oncology Shanghai Medical CollegeFudan University department of Integrative oncology Fudan University Shanghai Cancer Center

Polyphyllin I(PPI), a main steroidal saponin found in Rhizoma Paridis, which has anti-inflammatory, antiviral, antifibrosis, anthelmintic and hemostatic effects in Traditional Chinese Medicine(TCM). Modern pharmacological studies indicated that polyphyllin I has potent cytotoxicity and has potential to develop into an anticancer agent, however the molecular mechanism of the anticancer effects has not been fully elucidated. Therefore, this review outlines recent developments on mechanisms of PPI against different types of cancer. Furthermore, we also make an overview of the mechanisms identified so far. These meaningful findings may provide novel insights on exploiting polyphyllin I as a new antitumor agent.

关键词： Rhizoma Paridis Steroidal saponin Polyphyllin Ⅰ Antitumor mechanisms

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oncology and Translational Medicine 2019年第2期5卷 91-97页

作者： Hua Zheng Yuan Gao Zan Liu Zhe Qian Tongmei Zhang Jie Li Hongmei Zhang Qunhui Wang Fanbin Hu Baolan Li department of Medical oncology Beijing Chest Hospital Capital Medical University

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical *** Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

关键词： lung neoplasms EGFR uncommon mutation G719X target therapy

The impact of urological resection and reconstruction on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

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Asian Journal of Urology 2018年第3期5卷 194-198页

作者： Grace Hwei Ching Tan Nicholas B.Shannon Claramae Shulyn Chia Lui Shiong Lee Khee Chee Soo Melissa Ching Ching Teo Division of Surgical oncology National Cancer Centre SingaporeSingapore Duke-NUS Medical School Singapore department of Urology Singapore General HospitalSingapore

Objective:Cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are increasingly being used to treat peritoneal *** resections and reconstruction(URR)are occasionally performed during the *** aim to evaluate the impact of these procedures on peri-operative outcomes of CRS and HIPEC ***:A retrospective review of a prospectively maintained database of all patients who underwent CRS-HIPEC from April 2001 to February 2016 was *** between patients who had surgery involving,and not involving URR were *** outcomes were the rate of major complications and the duration of stay in the intensive care unit(ICU)and *** outcomes were that of overall survival(OS)and prognostic factors that would indicate a need for ***:A total of 214 CRS-HIPEC were performed,21 of which involved a *** clinical characteristics did not vary between the groups(URR *** URR).Urological resections comprised of 52%bladder resections,24%ureteric resections,and 24%involving both bladder and ureteric *** bladder defects were closed primarily while ureteric reconstructions consisted of two end-to-end anastomoses,one ureto-uretostomy,five direct implantations into the bladder and three boari *** were more frequently required in patients with colorectal peritoneal disease(p Z 0.029),but was not associated with previous pelvic surgery(76%vs.54%,p Z 0.065).Patients with URR did not suffer more serious complications(14%vs.24%,p Z 0.42).ICU(2.2 days vs.1.4 days,p Z 0.51)and hospital stays(18 days vs.25 days,p Z 0.094)were not significantly *** a URR did not affect OS(p Z 0.99),but was associated with increased operation time(570 min vs.490 min,p Z 0.046).Conclusion:While concomitant URR were associated with an increase in operation time,there were no significant differences in postoperative complications or *** with colorectal peritoneal metastases a

关键词： Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Peritoneal carcinomatosis Urological procedures Urological reconstruction

Synthesis of a copolymer carrier for anticancer drug luteolin for targeting human breast cancer cells

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Journal of Traditional Chinese Medicine 2019年第4期39卷 474-481页

作者： Mahin Maleki Ali Aidy Elahe Karimi Shaahin Shahbazi Nader Safarian Naser Abbasi Biotechnology and Medicinal Plants Research Center Ilam University of Medical SciencesIlamIran department of Chemistry Ilam BranchIslamic Azad UniversityIlamIran department of Internal Medicine Faculty of MedicineIlam University of Medical SciencesIlamIran department of Medical oncology and Hematology Faculty of MedicineTehran University of Medical ScienceTehranIran department of Pharmacology Medical SchoolIlam University of Medical SciencesIlamIran

OBJECTIVE: To focus a new chemoprevention approach that uses nanotechnology to deliver luteolin to human breast cancer cells(MCF-7), and its underlying ***: Water-soluble copolymer-encapsulated nanoparticle-luteolin(CENL) was formulated using the hydrophobic drug luteolin. The ability to load and release he anticancer drug into/from the synthesized hyperbranched polyester was evaluated by high-performance liquid *** successful synthesis of CENL was supported by analytical techniques including fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography,and dynamic light scattering. Cell viability was measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide color method. Reactive oxygen species(ROS) were measured using a dichlorofluorescein probe and intracellular calcium(Cai2+) was evaluated with a flu3-AM ***: The results showed that the drug delivery system is stable and that the loading capacity is high. Treatment with nanoparticles containing luteolin and free luteolin resulted in cell death in breast cancer cells at high concentrations (IC50(33 ± 4) and(48 ± 6) μM, respectively)At high concentrations,CENL reduced cell viability and increased ROS and Cai2+ ***: Our results demonstrate that CENL has potential for human breast cancer treatment.

关键词： Polymers Materials testing Drug delivery systems Luteolin