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Management of recurrent rectal cancer:A population based study in greater amsterdam

World Journal of Gastroenterology 2008年第39期14卷 6018-6023页

作者： Roel Bakx Otto Visser Judith Josso Sybren Meijer J Frederik M Slors J Jan B van Lanschot Department of Surgery Academic Medical CentreAmsterdam AZ 1105Netherlands comprehensive cancer centre amsterdam Amsterdam CX 1066Netherlands Department of Surgery Free University Medical CentreAmsterdam HV 1081Netherlands Presently at the Erasmus Medical Center Rotterdam CE 3015Netherlands

AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the amsterdam cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.

关键词： Rectal cancer Total mesorectal excision Local recurrence Relative survival

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The PI3K/Akt/m TOR pathway in ovarian cancer: therapeutic opportunities and challenges

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Chinese Journal of cancer 2015年第1期34卷 4-16页

作者： Bianca Cheaib Aurélie Auguste Alexandra Leary Gynecological Unit Department of MedicineGustave Roussy Comprehensive Cancer Centre Gynecological Tumor Team Translational Research Laboratory U981 Gustave Roussy Comprehensive Cancer Centre

The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.

关键词： mTOR 信号通路卵巢癌磷脂酰肌醇3激酶 AKT 激素疗法治疗临床试验

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Regional but fatal: Intraperitoneal metastasis in gastric cancer

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World Journal of Gastroenterology 2016年第33期22卷 7478-7485页

作者： Jia Wei Nan-Die Wu Bao-Rui Liu comprehensive cancer centre of Drum Tower Hospital Medical School of Nanjing UniversityClinical Cancer Institute of Nanjing University

Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.

关键词： Gastric cancer Intraperitoneal metastasis Regional metastasis Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy

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MicroRNAs:Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential

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World Journal of Gastroenterology 2014年第38期20卷 13658-13666页

作者： Christiane Matuszcak Joerg Haier Richard Hummel Kirsten Lindner Department of General and Visceral Surgery Muenster University Hospital comprehensive cancer centre Muenster University Hospital

Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in *** authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.

关键词： MicroRNAs Biomarker Chemoresistance Gastric cancer Diagnostic Therapeutic

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Jug-PLGA-NPs, a New Form of Juglone with Enhanced Efficiency and Reduced Toxicity on Melanoma

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Chinese Journal of Integrative Medicine 2022年第10期28卷 909-917页

作者： YUE Wu-heng QIN Lan-qun CAI Juan MEI Rui QIAN Han-qing ZOU Zheng-yun The comprehensive cancer centre of Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing(210008)China Department of Oncology Taicang TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhouJiangsu Province(215499)China The comprehensive cancer centre of Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing(210008)China The comprehensive cancer centre of Nanjing Drum Tower Hospital Medical School of Nanjing University&Clinical Cancer Institute of Nanjing UniversityNanjing(210008)China

Objective: To verrify the anti-tumor efficacy and toxicity between juglone(Jug) and Jug-loaded poly lactic-co-glycolic acid(PLGA) nanoparticles(Jug-PLGA-NPs). Methods: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug(2, 3, 4 μg/mL) and Jug-PLGA-NPs(Jug: 2, 3, 4 μg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. Results: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo(P<0.05 or P<0.01) with acceptable biocompatibility. Conclusions: Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.

关键词： juglone PLGA nanoparticles malignant melanoma Jug-PLGA-NPs

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Bimetallic Single‑Atom Catalysts for Water Splitting

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Nano-Micro Letters 2025年第1期17卷 1-45页

作者： Megha A.Deshmukh Aristides Bakandritsos Radek Zbořil Nanotechnology centre Centre for Energy and Environmental TechnologiesVŠB–Technical University of Ostrava17.listopadu 2172/1570800 Ostrava‑PorubaCzech Republic Regional centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute(CATRIN)Palacky University OlomoucŠlechtitelů241/2778371 Olomouc–HoliceCzech Republic

Green hydrogen from water splitting has emerged as a critical energy vector with the potential to spearhead the global transition to a fossil fuel-independent *** field of catalysis has been revolutionized by single-atom catalysts(SACs),which exhibit unique and intricate interactions between atomically dispersed metal atoms and their ***,bimetallic SACs(bimSACs)have garnered significant attention for leveraging the synergistic functions of two metal ions coordinated on appropriately designed *** offer an avenue for rich metal–metal and metal–support cooperativity,potentially addressing current limitations of SACs in effectively furnishing transformations which involve synchronous proton–electron exchanges,substrate activation with reversible redox cycles,simultaneous multi-electron transfer,regulation of spin states,tuning of electronic properties,and cyclic transition states with low activation *** review aims to encapsulate the growing advancements in bimSACs,with an emphasis on their pivotal role in hydrogen generation via water *** subsequently delve into advanced experimental methodologies for the elaborate characterization of SACs,elucidate their electronic properties,and discuss their local coordination ***,we present comprehensive discussion on the deployment of bimSACs in both hydrogen evolution reaction and oxygen evolution reaction,the two half-reactions of the water electrolysis process.

关键词： Single-atom catalysts Single-atom dimers Hydrogen evolution Oxygen evolution Water splitting

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Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells

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Bioactive Materials 2024年第7期37卷 331-347页

作者： Aoxing Chen Junmeng Zhu Rui Liu Yi Mei Lin Li Yue Fan Yaohua Ke Baorui Liu Qin Liu Department of Oncology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineThe Clinical Cancer Institute of Nanjing University321 Zhongshan RoadNanjing210008China The comprehensive cancer centre Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University321 Zhongshan RoadNanjing210008China The comprehensive cancer centre China Pharmaceutical University Nanjing Drum Tower Hospital321 Zhongshan RoadNanjing210008China

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune *** previous studies,FOLactis was designed,which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand,leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral ***,it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal *** patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors,intratumoral injection is not feasible and peritumoral maybe a better ***,an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 *** injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells(TEM),playing the role of artificial lymph ***,administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors,resulting in an extended survival ***,these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

关键词： cancer immunotherapy Engineered bacteria Thermos-sensitive hydrogel Localized drug delivery Artificial lymph node

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Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第29期23卷 5395-5404页

作者： Jie Shen Li-Feng Wang Zheng-Yun Zou Wei-Wei Kong Jing Yan Fan-Yan Meng Fang-Jun Chen Juan Du Jie Shao Qiu-Ping Xu Hao-Zhen Ren Ru-Tian Li Jia Wei Xiao-Ping Qian Bao-Rui Liu comprehensive cancer centre of Drum Tower Hospital Medical School of Nanjing University Clinical Cancer Institute of Nanjing University Department of Hepatobiliary Surgery Drum Tower Hospital Medical School of Nanjing Universit-y

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with *** Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side *** Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

关键词： Personalized peptide vaccination TOMO radiotherapy Cytotoxic lymphocytes Hepatocellular carcinoma

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Osteocyte morphology and orientation in relation to strain in the jaw bone

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International Journal of Oral Science 2018年第1期10卷 36-43页

作者： Vivian Wu René F. M. van Oers Engelbert A. J. M. Schulten Marco No Helder Rommel G. Bacabac Jenneke Klein-Nulend Department of Oral Cell Biology Academic Centre for Dentistry Amsterdam (ACTA) Amsterdam Movement Sciences University of Amsterdam and Vrije Universiteit Amsterdam Amsterdam The Netherlands Department of Dental Materials Science Academic Centre for Dentistry Amsterdam (ACTA) Amsterdam Movement Sciences University of Amsterdam and Vrije Universiteit Amsterdam Amsterdam The Netherlands Department of Oral and Maxillofacial Surgery VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA) Amsterdam Movement Sciences Amsterdam The Netherlands Department of Physics Medical Biophysics Group University of San Carlos Cebu City Philippines

Bone mass is important for dental implant success and is regulated by mechanoresponsive osteocytes. We aimed to investigate the relationship between the levels and orientation of tensile strain and morphology and orientation of osteocytes at different dental implant positions in the maxillary bone. Bone biopsies were retrieved from eight patients who underwent maxillary sinus-floor elevation with β-tricalcium phosphate prior to implant placement. Gap versus free-ending locations were compared using 1) a three-dimensional finite-element model of the maxilla to predict the tensile strain magnitude and direction and 2) histology and histomorphometric analyses. The finite-element model predicted larger, differently directed tensile strains in the gap versus freeending locations. The mean percentage of mineralised residual native-tissue volume, osteocyte number(mean ± standard deviations:97 ± 40/region-of-interest), and osteocyte shape(90% elongated,10% round) were similar for both locations. However, the osteocyte surface area was 1.5-times larger in the gap than in the free-ending locations, and the elongated osteocytes in these locations were more cranially caudally oriented. In conclusion, significant differences in the osteocyte surface area and orientation seem to exist locally in the maxillary bone, which may be related to the tensile strain magnitude and orientation. This might reflect local differences in the osteocyte mechanosensitivity and bone quality, suggesting differences in dental implant success based on the location in the maxilla.

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