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Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma

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Cancer Drug Resistance 2023年第2期6卷 314-326页

作者： Monica Sheila Chatwal Jad Chahoud Philippe e.spiess Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA

Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality *** newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term *** of resistance have been explored in a variety of solid tumors,including *** upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in ***,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal *** the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.

关键词： Metastatic clear-cell renal-cell carcinoma immune therapy checkpoint inhibitor resistance chimeric antigen receptor T-cell therapy

Updates in the use of radiotherapy in the management of primary and locally-advanced penile cancer

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Asian Journal of Urology 2022年第4期9卷 389-406页

作者： Akshar Patel Arash O.Naghavi Peter A.Johnstone Philippe e.spiess G.Daniel Grass University of South Florida Morsani College of Medicine TampaFLUSA Department of Radiation Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFLUSA Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFLUSA

Objective:Penile cancer is a rare malignancy in most developed countries,but may represent a significant oncologic challenge in certain African,Asian,and South American *** treatment approaches have been described in penile cancer,including *** review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated *** addition,we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment ***:Peer-reviewed manuscripts related to the treatment of penile cancer with radio-therapy were evaluated by a PubMed search(1960-2021)in order to assess its role in the definitive and adjuvant *** manuscripts were also evaluated for descriptions of radiation-related ***:Though surgical resection of the primary is an excellent option for tumor control,select patients may be treated with organ-sparing radiotherapy by either external beam radiation or *** from randomized controlled trials comparing radiotherapy and surgery are lacking,and thus management is frequently determined by institutional practice patterns and available ***,this lack of clinical trial data leads to divergence in opinion regarding lymph node *** is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery *** toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal *** differences in tumor biology,based on human papillomavirus infection,may help aid future prognostic and predictive models in patient risk stratification or treatment ***:Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment *** a result,the goal of management

关键词： Brachytherapy Chemoradiation Radiation Radiotherapy Penile cancer Squamous cell carcinoma of the penis Penile-sparing Penile metastase Human papillomavirus

Genitourinary melanoma:An overview for the clinician

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Asian Journal of Urology 2022年第4期9卷 407-422页

作者： Danielle K.DePalo Kelly M.elleson Michael J.Carr Philippe e.spiess Jonathan S.Zager Department of Cutaneous Oncology Moffitt Cancer CenterTampaFLUSA Department of Surgery University of LouisvilleLouisvilleKYUSA Department of Genitourinary Oncology Moffitt Cancer CenterTampaFLUSA

Genitourinary (GU) melanoma is a rare presentation of melanoma accounting for approximately 0.5% of all *** melanomas include primary melanomas of the vulva,vagina,uterine cervix,ovary,penis,scrotum,urethra,bladder,ureter,and *** melanomas are often diagnosed in advanced stages and stigma is thought to contribute to delays in *** the likely diagnosing provider,it is imperative that dermatologists,urologists,and gynecologists are aware of these uncommon sites of *** there have been major advances in the treatment of melanomas as a whole in the last 10 years,their applications to GU melanomas have often been *** melanomas have not been included in many of the major phase II clinical trials which brought contemporary advanced treatments to market and the prognoses for GU melanomas remain *** to the rarity of GU melanomas,much of the literature provides gener alized recommendations across multiple different organs affected by GU melanomas or omits certain topics,making it difficult to appreciate the funda-mentals of the individual *** review aimed to provide background information on the pathogenesis and epidemiology of the different sites of GU melanomas and categorize data specific to the presentation,staging,treatment,and prognosis of each type of GU melanoma to guide the *** was also meant to encourage a multidisciplinary approach to the management of these patients as it spans the expertise of surgical oncologists,medical oncologists,radiation oncologist,dermatologists,urologists,and gynecologists.

关键词： Genitalia Female Male Melanoma Rare diseases Staging Treatment Urinary tract

Genitourinary manifestations of Lynch syndrome in the urological practice

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Asian Journal of Urology 2022年第4期9卷 443-450页

作者： Chiara Lonati Claudio Simeone Nazareno Suardi Philippe espiess Andrea Necchi Marco Moschini Urology Unit ASST Spedali Civili di BresciaDepartment of Medical and Surgical SpecialtiesRadiological Science and Public HealthUniversity of BresciaBresciaItaly Department of Urology Luzerner KantonsspitalLucerneSwitzerland Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTamplaFLUSA University Vita-Salute San Raffaele MilanItaly Department of Medical Oncology IRCCS San Raffaele Hospital and Scientific InstituteMilanItaly Division of experimental Oncology/Unit of Urology Urological Research InstituteIRCCS Ospedale San RaffaeleMilanItaly

Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in ePCAM *** a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general *** aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening ***:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was ***:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general *** diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary *** current european Association of Urology(eAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of *** diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and ***,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic *** urological malignancies other than UTUC should be included in the LS tumor spectrum is still cont

关键词： Hereditary disease Hereditary nonpolyposis colorectal cancer Lynch syndrome Mismatch repair Upper tract urothelial carcinoma

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基于知识的专题制图系统——另一种途径

黑龙江测绘 1994年第3期17卷 53-59页

作者： e.Hutzler e.spiess(Zurich cH) 童扬芬武汉测绘科技大学

随着各个领域的基于知识系统的发展,大量专题制图设计问题有希望得到解决。当数据输入和用户要求格式化时,系统可在没有任何干预的情况下通过规则库指导完成全部必要的步骤。这样的一种方法将完全同交互式设计方式形成对比,而后一种方... 详细信息

随着各个领域的基于知识系统的发展,大量专题制图设计问题有希望得到解决。当数据输入和用户要求格式化时,系统可在没有任何干预的情况下通过规则库指导完成全部必要的步骤。这样的一种方法将完全同交互式设计方式形成对比,而后一种方式完全是在有经验的制图员的操作控制之下进行的。考虑到问题的复杂性,采用规则引导和规则支持是必要的。规则也许有助于利用复杂相同步骤来代替通过全面而巨大的专家系统寻求解决方法的方式,但这似乎不现实。因为大量专题制图比这个目的复杂得多。本文提出的方案是与交互式模式并驾齐驱的逐渐形成的专家模型,并且对原型中几个部分的设计结构作了解释和阐述。

关键词：专题制图制图专家系统

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Simplified seismic scenario analysis of existing masonry buildings accounting for local site effects

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Frontiers of Structural and Civil engineering 2024年第2期18卷 309-318页

作者： Ayşe e.ÖZSOYÖZBAY Işıl SANRI KARAPINAR Zehra N.KUTLU İsmail e.KILIÇ Department of Civil engineering Maltepe UniversityIstanbul 34857Turkey School of engineering and Construction Oryx Universal CollegeDoha 12253Qatar

This study discusses the effects of local sites and hazard amplification on the seismic vulnerability assessment of existing masonry *** this context,a rapid seismic evaluation procedure was implemented on an old masonry building stock in the historical center Galata,located inİstanbul,to determine the seismic risk priority of the built *** scenarios were generated for all soil classes,different moment magnitudes,and source-to-site distances to obtain more accurate results for the seismic vulnerability assessment of the studied building ***,damage distributions estimated under nine different scenarios with/without site effects were compared and illustrated in maps to discuss changes in vulnerability owing to amplification *** this study,by re-examining the rapid seismic evaluation procedure by including geo-hazard-based assessment,the importance of site effects on the vulnerability and risk assessment of built heritage was *** proposed framework integrating field data and local site effects is believed to advance the current applications for vulnerability assessment of masonry buildings and provide an improvement in the application of rapid seismic assessment procedures with more reliable results.

关键词： masonry buildings seismic vulnerability assessment cultural heritage local site effect

CLASSIFICATIONS OF DUPIN HYPeRSURFACeS IN LIe SPHeRe GeOMeTRY

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Acta Mathematica Scientia 2024年第1期44卷 1-36页

作者： Thomas e.CeCIL Department of Mathematics and Computer Science College of the Holy CrossWorcesterMA01610USA

This is a survey of local and global classification results concerning Dupin hypersurfaces in S^(n)(or R^(n))that have been obtained in the context of Lie sphere *** emphasis is on results that relate Dupin hypersurfaces to isoparametric hypersurfaces in *** with these classification results,many important concepts from Lie sphere geometry,such as curvature spheres,Lie curvatures,and Legendre lifts of submanifolds of S^(n)(or R^(n)),are described in *** paper also contains several important constructions of Dupin hypersurfaces with certain special properties.

关键词： Dupin hypersurfaces isoparametric hypersurfaces Lie sphere geometry Lie sphere transformations Lie curvatures

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Investigating the impact of the universal function of the nuclear proximity potential in heavy-ion fusion cross sections

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Communications in Theoretical Physics 2024年第5期76卷 86-93页

作者： R Gharaei e Sarvari Department of Physics Sciences FacultyHakim Sabzevari UniversityPO Box 397SabzevarIran Department of Physics Faculty of ScienceFerdowsi University of MashhadPO Box 91775-1436MashhadIran Science Faculty Department of PhysicsTarbiat Modares UniversityTehranIran

The fusion barriers and cross sections of 15 colliding systems with 320≤Z_(1)Z_(2)≤1512 are investigated in detail to understand the influence of the universal function of proximity potential formalism in the heavy-ion fusion *** realize this goal,we select three versions of the phenomenological proximity potentials,including Prox.77,Zhang 2013,and Guo 2013,to calculate the nucleus-nucleus *** experimental fusion cross sections for the selected reactions are analyzed using the standard coupled-channel calculations,including couplings to the low-lying 2^(+)and 3^(-)states in the target and *** calculated results show that the universal functions of the Guo 2013 and Prox.77 models provide the lowest and highest fusion barriers,*** addition,it is found that the height of the fusion barriers is enhanced by increasing the mass number of the projectile from light to heavy *** highest sensitivity to the mass number of the projectile belongs to the results of Prox.77.A discussion is also presented on the influence of the universal function on the radial behavior of the interaction potential in the allowed region for overlapping *** results reveal that the best fit to the experimental data of the fusion cross sections for the reactions involving light and medium nuclei is obtained using the universal function of the Zhang 2013 *** the heavier systems,the results of the Guo 2013 model at sub-barrier energies provide a good description of the available data.

关键词： fusion reactions proximity-type potentials universal function coupled-channel calculations

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Are hydrides under high-pressure-high-temperature superconductors?

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National Science Review 2024年第7期11卷 9-12页

作者： J.e.Hirsch Department of Physics University of California

Contrary to the current consensus, I argue that the existing evidence for high-temperature superconductivity in hydrides under high pressure is not compelling. I suggest that the focus of the field should urgently shift to establish unequivocally experimentally whether or not superconductivity in pressurized hydrides exists, instead of continuing to search for new materials that might show elusive signals of unproven superconductivity at ever higher temperatures. The implications of a negative finding for the theoretical understanding of superconductivity are discussed.

关键词： Hydrides