TumorFisher CTC detection technology for the treatment decision of anti-PD-1/PD-L1 in advanced hepatocellular carcinoma and its efficacy evaluation：a case report and literature review / 中国肿瘤生物治疗杂志

@#[摘 要] 肝细胞癌（HCC）的发病率和病死率正在逐年增长，严重威胁人类的健康和生命。近年来，以PD-1/PD-L1抑制剂为代表的免疫治疗迅速发展，但对晚期HCC疗效有限。治疗中实时监测循环肿瘤细胞（CTC）PD-L1表达，是评估免疫治疗有效性的重要指标之一。本案例通过TumorFisher检测技术实时监测1例HCC患者免疫治疗前后总CTC数及PD-L1+ CTC个数，结合影像学和血清学检查结果进一步评估患者免疫治疗疗效。患者治疗前总CTC数为5个/2 mL，PD-L1+ CTC为5个/2 mL，PD-L1+ CTC/总CTC为100%。用PD-1/PD-L1抑制剂行3周期免疫治疗后，PD-L1+ CTC/总CTC逐渐降低，肿瘤缩小，血清AFP及PIVKA-Ⅱ逐渐下降，PD-L1+ CTC/总CTC变化与肿瘤标志物、MRI检查结果一致。PD-L1+ CTC/总CTC可作为HCC免疫治疗疗效评估的辅助指标。

Minimal residual disease in solid tumors: an overview / 医学前沿

Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment.

Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca

Simulation and Analysis of Capture Characteristics of Circulating Tumor Cells Based on Unidirectional Fluid-Solid Interaction Method / 医用生物力学

Objective To study movement process of circulating tumor cells (CTCs) in the blood and mechanism of CTC capture by CellCollector, and reveal relationship between the detected CTC numbers and the actual CTC concentration in the body. Methods Based on Fluent and EDEM software, the unidirectional fluid-solid interaction method was applied to establish a two-phase flow model, including the hemodynamic model and the CTC transport model, and capture simulations under different CTC concentration conditions were conducted. Results The number of CTCs captured by CellCollector was significantly positively correlated with the CTC concentration in the body. When the CTC concentration was low, CTCs could only be captured in several time intervals, and the capture had a certain contingency; as the concentration increased, the uniformity of CTC capture over time became better, and the total number of captures also increased. Conclusions Through the fitting of simulation results, analytical quantitative relationship between the captured CTC number and the CTC concentration in the body is preliminarily given, which provides theoretical basis and mechanical explanation for the clinical use of CellCollector.

Magnetic nanocarriers for the detection of circulating tumor cells / 中国肿瘤生物治疗杂志

@#[摘 要] 循环肿瘤细胞（circulating tumor cell，CTC）是从原发肿瘤分离进入外周血或淋巴循环的肿瘤细胞，与肿瘤转移密切相 关。CTC作为液体活检重要标志物之一，支持实时动态重复检测，对于肿瘤的早期筛查、转移抑制、预后评估、复发监测、个性化 治疗指导具有重要意义。然而CTC在血液中含量极低，寻找稳定性好、灵敏度高及特异性强的CTC检测方法是当前研究的热 点。近年来，磁性纳米载体由于生物相容性好、表面易修饰和磁响应速度快等优势在CTC检测中受到广泛关注。本文阐述了 CTC检测的意义，系统归纳了磁性纳米载体用于CTC检测的设计方案，通过巧妙设计构建理想的磁性纳米载

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Biomimetic nanoparticles for inflammation targeting

There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.

Perfil da população idosa que procura o centro de referência em DST/aids de Passos/MG / Profile of the aging population that looks for the DST and aids reference center in Passos/MG

Introdução: falar sobre a sexualidade e o envelhecimento, nos dias atuais, significa abordar dois temas fascinantes, mas, ao mesmo tempo, ainda repletos de preconceitos e tabus. Sentimentos sexuais, necessidades sexuais e relações sexuais não são só um privilégio de jovens; com o aumento da expectativa de vida, os idosos brasileiros passam a vivenciar este processo com maior intensidade. Objetivo: caracterizar a população idosa que procurou o Centro de Testagem e Aconselhamento, referência em Doenças Sexualmente Transmissíveis (DST)/aids, no período de 1992 a 2009, em Passos/MG. Métodos: trata-se de uma pesquisa descritiva, de abordagem quantitativa, que orientou a coleta dos dados a partir de consulta a 113 prontuários dos idosos que procuram o serviço, desde sua abertura, em 1992, até 2009; a organização dos dados se deu em tabelas e gráficos, bem como a análise estatística efetuada. Resultados: os dados assinalam predominância de idosos do sexo masculino 74,34%, 51,33% entre a faixa etária de 60 a 65 anos, 35,40% com escolaridade do ensino fundamental e médio, 40,85% casados, 40,70% procuraram o Centro devido à exposição a uma situação de risco, 71,71% são heterossexuais e 66,37% têm relação sexual desprotegida. Conclusão: por este perfil, destaca-se a ampliação dos riscos de contágio e evolução epidemiológica do HIV/aids entre os idosos, indicando a necessidade de intensificar ações preventivas em DST/aids junto a esta população, para que tenham uma vida sexual saudável e segura.

Sexuality and aging nowadays mean talking about two fascinating themes, but at the same time, it is still full of prejudice and taboos. Sexual feelings, needs and relationships are not a privilege only of young people, and with the increase of life expectancy, brazilian mature people started living this process with greater intensity. Objective: to characterize the profile of the aging population who were assisted in the CTC (Counseling and Testing Center) at a STD/Aids Reference Center from 1992 to 2009 in Passos/MG. Methods: it is a descriptive research with quantitative approach, which oriented the data collection from the consultation of 113 files of elderly people who were assisted since the opening of the Reference Center in 1992 until 2009; the organization was shown in graphs and tables as well as the statistics analysis. Results: the data have shown a predominance of 74,34% masculine elderly people, between 60 to 65 years old (51,33%), 35,40% have finished high school and junior high school, 40,85% are married, 40,70% needed the Reference Center due to the exposition to a risk situation, 71,71% are heterosexuals, and 66,37% have unprotected sexual intercourse. Conclusion: with this profileit is highlighted an increase of risk of contamination and the epidemiological evolution of HIV among the elderly, indicating the necessity of developing preventive actions in STD/aids with this population for a safe and healthy sexual life.

Propriedades químicas de um Argissolo tratado sucessivamente com composto de lixo urbano / Chemical properties of an Ultisol successively treated with municipal waste compost

Com o objetivo de avaliar as alterações em algumas propriedades químicas do solo sob adição sucessiva de composto de lixo urbano, conduziu-se um experimento a campo, em um solo Argissolo Vermelho de textura média na Estação Experimental Agronômica da UFRGS. Os tratamentos constaram de cinco doses de composto (0, 20, 40, 80 e 160t ha-1), de um tratamento com adubo mineral e uma testemunha (Calagem e NPK), com aplicações sucessivas por um período de quatro anos. A adição de composto no solo aumentou o pH, CTC, C orgânico, N total, P e Na extraíveis, bem como da relação de adsorção de sódio (RAS), Ca e Mg trocáveis e o teor de K extraível após a terceira aplicação. O Al trocável teve os seus teores diminuídos após aplicações sucessivas de composto. Os resultados permitiram concluir que aplicação de até 80t ha-1 por ano de composto de lixo urbano pode ser considerada como adequada para melhorar e, ou, manter as propriedades químicas do solo.

In order to assess the changes in some chemical properties of soil under the successive addition of urban waste compost, it was conducted a field experiment in an Ultisol soil at Agronomic Experimental Station of UFRGS. The treatments consisted of five successive applications of different doses of municipal solid waste compost (0, 20, 40, 80 and 160t ha-1) for a period of four years and a comparative treatment with mineral fertilizer and a control (without compost and fertilization). The addition of the compost increased soil pH, CEC, organic C, total N, extractable P and Na and the sodium adsorption ratio (SAR), calcium, and magnesium and extractable K after the third application. The exchangeable Al had their levels reduced by successive applications of compost. The results showed that application of up to 80t ha-1 yr-1 of urban waste compost can be the dose recommended to improve and maintain the chemical properties of soil.

Teores de As, Pb, Cd e Hg e fertilidade de solos da região do Vale do Alto Guaporé, sudoeste do estado de Mato Grosso / Contents of As, Pb, Cd e Hg and fertility of soils of Vale do Alto Guapore region, south-west of Mato Grosso state

O diagnóstico da fertilidade e teores de elementos-traço (ETs) em solos é importante, pois estes dados são escassos na literatura para áreas de transição Pantanal-Cerrado-Floresta Amazônica. Esse trabalho avaliou diversos parâmetros relacionados à fertilidade, teores biodisponíveis de Fe, Mn, Zn, Cu e B e semitotais de As, Cd, Hg e Pb de solos do Vale do Alto Guaporé, região sudoeste do estado de Mato Grosso. Foram coletadas amostras de solos (0-0,20 e 0,20-0,40 m de profundidade) em áreas de vegetação nativa (VN), pastagem (AP), cultura anual (CA) e garimpo de ouro (G). As amostras foram analisadas conforme métodos de rotina para avaliação da fertilidade do solo e ETs pelo método SW-3051A e os resultados médios comparados com os valores de referência de qualidade (VRQ) para solos estipulados pela Companhia de Tecnologia de Saneamento Ambiental (CETESB). Teores mais elevados de As e Hg foram verificados em VN e G com médias, respectivamente, iguais a 43,9 e 101,13 para o As; e 0,12 e 0,14 mg kg-1 para o Hg. Exceto Pb, vários locais de amostragem apresentaram teores dos ETs superiores ao VRQ: 46% em VN; 60% em G; 28% em CA; e 44% em AP, para o As; 20,8; 50; 55; e 22% em VN, G, CA e AP, respectivamente, para o Cd; 75; 65 e 67% das áreas de VN, G e CA e AP, respectivamente, para o Hg. A saturação por bases foi alta (60-80%) em 51,5% das amostras, enquanto o P foi baixo em todas áreas. Valores de referência de qualidade de solo para o As e Hg devem ser estipulados para solos dessa região, tendo em vista que os teores observados em áreas nativas foram superiores ao VRQ.

The fertility and trace elements diagnosis of soils is important for agricultural and environmental purposes, because there is little data available on the Pantanal-Cerrado-Floresta Amazônica transitional areas. This work evaluated many parameters relative to the fertility, Fe, Mn, Zn, Cu and B bioavailability, and total content of As, Cd, Hg and Pb in soils of the Vale do Guaporé, in the south-western region of Mato Grosso. Soil samples were collected in depths of 0-0,2 and 0,20-0,40 m in native vegetation, pasture, annual crop and gold mineration areas. These samples were analyzed for fertility according to Embrapa methodologies and trace elements by the SW3051 methods; and the average results were compared with quality reference values (VRQ) of soils of São Paulo stipulated by the Company of Technology of Environment Sanitation (CETESB). The Pb contents in the majority of samples were below the VRQ. In relation to As, many samples showed contents above the VRQ: 45,8% in native vegetation areas; 60% in the gold mineration areas; 28% in annual crop areas; and 44% in the pasture areas. The Cd contents too were above the VRQ: 20,8; 50; 55,5; and 22% for native vegetation, gold mineration, annual crop and pasture areas. Similar behavior was observed for Hg, which presented 75; 65; and 67% for native vegetation; gold mineration; and annual crop and pasture areas, respectively, with mean contents above the VRQ. About pH, around 68% of the samples presented values between 6,1 and 7,0 and the values of base saturation (V) were high (60-80%) for 51,5% of the points sampled. However, the mean P content was short in the whole area. The comparison of As, Cd and Hg contents with the VRQ of soils showed that it is necessary to determine these values for the state of Mato Grosso, keeping in view that the total contents of these elements observed in native areas were superior to the VRQ.

Fundamental Elements for Successful Performance of CT Colonography (Virtual Colonoscopy)

There are many factors affecting the successful performance of CT colonography (CTC). Adequate colonic cleansing and distention, the optimal CT technique and interpretation with using the newest CTC software by a trained reader will help ensure high accuracy for lesion detection. Fecal and fluid tagging may improve the diagnostic accuracy and allow for reduced bowel preparation. Automated carbon dioxide insufflation is more efficient and may be safer for colonic distention as compared to manual room air insufflation. CT scanning should use thin collimation of < or =3 mm with a reconstruction interval of < or =1.5 mm and a low radiation dose. There is not any one correct method for the interpretation of CTC; therefore, readers should be well-versed with both the primary 3D and 2D reviews. Polyps detected at CTC should be measured accurately and reported following the "polyp size-based" patient management system. The time-intensive nature of CTC and the limited resources for training radiologists appear to be the major barriers for implementing CTC in Korea.