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Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

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World Journal of Gastroenterology 2010年第38期16卷 4823-4831页

作者： Inti Zlobec Francesca Molinari Vittoria Martin Luca Mazzucchelli Piercarlo Saletti Rosangela Trezzi Sara De Dosso Tatjana Vlajnic Milo Frattini Alessandro Lugli institute for Pathology University Hospital Basel institute of Pathology Division of Medical oncology Institute of Southern Switzerland

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ***: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

关键词： Anti-epidermal growth factor receptor therapy Colorectal cancer K-RAS Prognosis Tumor budding

KRAS Exon 3 and PTEN Exon 7 Mutations in Small-cell Lung Cancer

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Current Medical Science 2019年第3期39卷 379-384页

作者： Lei LEI Zhi-ming JIANG Cheng-hui LI Hong-yang LU Zhejiang Key Laboratory of Diagnosis & Treatment Technology on thoracic oncology (Lung and Esophagus) Zhejiang Cancer Hospital Hangzhou 310022China Department of Medical oncology Zhejiang Cancer Hospital Hangzhou 310022China

Small cell lung cancer (SCLC) is recognized as one of the most aggressive and fatal malignant tumors. No significant improvement has been made to prolong the survival of SCLC patients. This study aimed to examine the mutation status of K-Ras (KRAS) and phosphatase and tensin homolog (PTEN) in SCLC patients in order to identify potential therapeutic targets for SCLC. Nineteen primary SCLC tumor specimens were enrolled in the study. Direct sequencing was perfonned to detect the mutations of KRAS exon 3 and PTEN exon 7 in the specimens. Kaplan- Meier and Cox regression analysis was performed to determine the overall survival (OS) of these SCLC patients. KRAS exon 3 mutation was found in 4 (21%) SCLC patients, and PTEN exon 7 mutation in only 1 (5%) SCLC patient. Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P0.05). Cox proportional hazards regression model indicated that extensive stage of disease was the only independent negative prognostic factor for OS in SCLC patients. In conclusion, KRAS exon 3 and PTEN exon 7 mutations had no significant impact on OS of SCLC patients. Further study is still necessary to validate the molecular profiles of SCLC.

关键词： gene Ras small cell lung carcinoma prognosis

Effect of ginseng polysaccharides and dendritic cells on the balance of Th1/Th2 T helper cells in patients with non-small cell lung cancer

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Journal of Traditional Chinese Medicine 2014年第6期34卷 641-645页

作者： Junjie Ma Huiping Liu Xiaolong Wang Basic Medical College of Nanjing University of Chinese Medicine Department of thoracic Surgery Chang Gung Memorial Hospital Department of thoracic Surgery BenQ Hospital Affiliated to Nanjing MedicalUniversity Department of oncology Jiangsu Shuyang Hospital of Traditional Chinese Medicine

OBJECTIVE: To investigate the effect of thorascopic administration of ginseng polysaccharides(GPS)plus dendritic cells(DC) on T helper cell type 1/T helper cell type 2(Th1/Th2) balance in patients with non-small cell lung cancer(NSCLC).METHODS: A total of 96 NSCLC patients were divided evenly into two groups. The control group was treated with DCs alone and the treatment group was treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically, once a week,4 times for 30 days, the patients' quality of life was measured with the Functional Assessment of Can-cer Treatment-Lung(FACT-L) questionnaire before and after treatment. Serum interferon-γ(INF-γ), interleukin-4(IL-4), IL-2 and IL-5 were examined before and after ***: The level of Th1 cytokines(INF-γ, IL-2)and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) increased in both treatment groups, while Th2cytokines(IL-4, IL-5) and FACT-L scores decreased(P<0.01). Furthermore, after treatment Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) were higher in the DCs +GPS group than in the control group(P<0.05). Conversely, FACT-L scores and Th2 cytokines(IL-4, IL-5)were higher in the control group than in the DCs +GPS group(P<0.05).CONCLUSION: The treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune function as compared with DCs alone. This was evident by increased expression of Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2(INF-γ/IL-4, IL-2/IL-5), as well as by decreased FACT-L scores and the expression of Th2 cytokines(IL-4,IL-5).

关键词： Panax Dendritic cells Carcinoma,non-small-cell lung Interferons Interleukins

CSPP1 preserves quiescent microtubule functions by dual-end capping

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Journal of Molecular Cell Biology 2024年第5期16卷 1-2页

作者： Marina Mapelli European institute of oncology IRCCS 20139 MilanoItaly

Microtubules(MTs)are cytoskeletal filaments composed of polarized arrays of globularα/β-tubulin dimers organized as hollow *** to this arrangement,MTs are mechanically rigid and can assemble into large intracellular structures that serve diverse cellular *** dividing cells,MTs organize bipolar mitotic spindles,ensuring equal segregation of sister chromatids and cor-rect placement of daughter cells into the tissue(Gudimchuk and McIntosh,2021;Lechler and Mapelli,2021).

关键词： functions. dividing preserve

Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer

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World Journal of Gastroenterology 2015年第43期21卷 12234-12248页

作者： Ken-ichi Fujita Yutaro Kubota Hiroo Ishida Yasutsuna Sasaki institute of Molecular oncology Showa University Department of Medical oncology Showa University School of Medicine

Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer(CRC) at the end of the last century,survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil,oxaliplatin and several molecularly-targeted anticancer drugs,resulting in the extension of overall survival to longer than 30 mo. Severe,occasionally life-threatening toxicity occurs sporadically,even in patients in relatively good condition who have a low risk of chemotherapyinduced toxicity,often causing the failure of irinotecanbased chemotherapy. Clinical pharmacological studies have revealed that such severe toxicity is related to exposure to SN-38 and genetic polymorphisms in UDPglucuronosyltransferase 1A1 gene. The large interand intra-patient variability in systemic exposure to SN-38 is determined not only by genetic factors but also by physiological and environmental factors. This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38,with the ultimate goal of achieving personalized irinotecan-based chemotherapy.

关键词： Irinotecan Metastatic colorectal cancer Survival a

Fumarate hydratase inactivation in renal tumors: HIF1α, NRF2, and "cryptic targets" of transcription factors

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Chinese Journal of Cancer 2012年第9期31卷 413-420页

作者： Aikseng Ooi Kyle A.Furge Laboratory of Interdisciplinary Urological oncology Van Andel Research Institute

Biallelic inactivation of fumarate hydratase (FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer (HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1α (HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2 (NRF2) through post-translational modification of its negative regulator. Kelch-like ECH-associated protein 1 (KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I (HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1).

关键词：富马酸盐转录因子酶失活肾肿瘤缺氧诱导因子1 竞争性抑制染色质结构水合

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第11期30卷 963-973页

作者： ZHANG Yi-lu JIAO Li-jing GONG Ya-bin XU Jian-fang NI Jian SHEN Xiao-yong ZHANG Jie ZHOU Di QIAN Cheng-xin WANG Qin YAO Jia-lin YANG Wen-xiao SU Ling-zi WANG Li-yu LI Jia-qi YAO Yi-qin ZHANG Yuan-hui WANG Yi-chao CHEN Zhi-wei XU Ling oncology Department Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China institute of Traditional Chinese Medicine oncology Shanghai University of Traditional Chinese MedicineShanghai 201203China oncology Department Shanghai Pulmonary HospitalShanghai Tongji UniversityShanghai 200433China thoracic Surgery Department Huadong HospitalShanghai Fudan UniversityShanghai 200040China thoracic Surgery Department Shanghai Cancer HospitalShanghai Fudan UniversityShanghai 200032China oncology Department Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China

Objective:To investigate whether the combination of chemotherapy with staged Chinese herbal medicine(CHM) therapy could enhance health-related quality of life(QoL) in non-small-cell lung cancer(NSCLC)patients and prolong the time before deterioration of lung cancer symptoms,in comparison to chemotherapy ***:A prospective,double-blind,randomized,controlled trial was conducted from December 14,2017 to August 28,2020.A total of 180 patients with stage ⅠB-ⅢA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM(chemo+CHM) group(120 cases) or chemotherapy combined with placebo(chemo+placebo) group(60 cases) using stratified blocking *** European Organization for Research and Treatment of Cancer(EORTC) Quality-of-Life-Core 30 Scale(QLQ-C30) was used to evaluate the patient-reported outcomes(PROs) during postoperative adjuvant chemotherapy in patients with early-stage *** events(AEs) were assessed in the safety ***:Out of the total 180 patients,173 patients(116in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO *** initial mean QLQ-C30 Global Health Status(GHS)/QoL scores at baseline were 57.16±1.64 and 57.67±2.25 for the two respective groups(P>0.05).Compared with baseline,the chemo+CHM group had an improvement in QLQ-C30GHS/QoL score at week 18 [least squares mean(LSM) change 17.83,95% confidence interval(CI) 14.29 to 21.38].Conversely,the chemo+placebo group had a decrease in the score(LSM change-13.67,95% CI-22.70 to-4.63).A significant between-group difference in the LSM GHS/QoL score was observed,amounting to 31.63 points(95% CI25.61 to 37.64,P<0.001).The similar trends were observed in physical functioning,fatigue and appetite *** week 18,patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group(P<0.001).The median time to deterioration

关键词： non-small-cell lung cancer adjuvant chemotherapy patient-reported outcome health-related quality of life Chinese herbal medicine

Present status and progress of neoadjuvant chemoradiotherapy for esophageal cancer

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Frontiers of Medicine 2013年第2期7卷 172-179页

作者： Jing Liu Jinbo Yue Ligang Xing Jinming Yu Department of Radiation oncology Shandong Cancer Hospital and InstituteJinan 250117China

Trimodality based on neoadjuvant chemoradiotherapy(nCRT)followed by surgery is gaining popularity as a treatment strategy for locally advanced esophageal *** this review,we summarize the role of nCRT and the recommended nCRT regimens based on clinical trials and *** analyze the relationship of nCRT with pathologic complete response(pCR)and then identify potential predictive markers of *** with surgery alone and neoadjuvant chemotherapy followed by surgery,trimodality provides longer survival and has the advantage of local control compared with definitive *** standard regimen is a platinum-based regimen with a radiation dose range of 41.4–50.4 Gy by conventional *** shows that patients with pCR tend to live longer than non-responders,indicating that pCR is a significant prognostic factor for patients with esophageal *** medicine requires predictive markers of individual patients based on their own ***,no definite marker is proved to be sufficiently sensitive and specific for use in clinical practice,although 18-fluorodeoxyglucose positron emission tomography shows promise in predicting response to nCRT.

关键词： esophageal cancer neoadjuvant chemoradiotherapy

Integration of stereotactic radiosurgery or whole brain radiation therapy with immunotherapy for treatment of brain metastases

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Chinese Journal of Cancer Research 2020年第4期32卷 448-466页

作者： Zhou Su Lin Zhou Jianxin Xue You Lu Department of thoracic oncology Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of oncology Sichuan Mianyang 404 HospitalMianyang 621000China

The prognosis of brain metastases(BM)is traditionally *** are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune checkpoint inhibitors,ICI)has demonstrated a survival advantage in multiple malignancies commonly associated with ***,radiotherapy and ICI both treat BM efficiently;hence,their combination seems *** this review,we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for ***,we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination *** from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and ***,there is a lack of conclusion about the definition of"simultaneous";the cumulative toxic effect of the combined therapies also requires further ***,ongoing and planned prospective trials are needed to further explore and validate the effect,safety,and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.

关键词： Immunotherapy radiotherapy immune checkpoint inhibitors brain metastases review