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Mapping bone marrow niches of disseminated tumor cells

Science China(Life Sciences) 2017年第10期60卷 1125-1132页

作者： Weijie Zhang Hin Ching Lo Xiang H.-F.Zhang Lester and Sue Smith Breast Center Baylor College of Medicine Houston TX 77030 USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX 77030 USA Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA Graduate Program in Integrative Molecular and Biomedical Sciences Baylor College of Medicine Houston TX 77030 USA McNair Medical Institute Baylor College of Medicine Houston TX 77030 USA

Breast cancer cells may disseminate early, before tumor diagnosis. disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.

关键词： disseminated tumor cells bone marrow niches hematopoietic stem cell niches 3D imaging

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Colorectal cancer and dormant metastases:Put to sleep or destroy?

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2304-2317页

作者： Marina A Senchukova Department of Oncology Orenburg State Medical UniversityOrenburg 460000Russia

After reading the review by An et al“Biological factors driving colorectal cancer metastasis”,which covers the problem of the metastasis of colorectal cancer(CRC),I had a desire to discuss with readers one of the exciting problems associated with dormant *** deaths from CRCs are caused by metastases,which can be detected both at diagnosis of the primary tumor and several years or even decades after *** is because tumor cells that enter the bloodstream can be destroyed by the immune system,cause metastatic growth,or remain dormant for a long *** tumor cells may not manifest themselves throughout a person’s life or,after some time and under appropriate conditions,may give rise to the growth of *** this editorial,we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation,as well as factors that contribute to the activation of dormant metastases in *** will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

关键词： Circulating tumor cells Colorectal cancer disseminated tumor cells Dormant metastases Metastases Premetastatic niche

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Prognostic relevance of minimal residual disease in colorectal cancer

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World Journal of Gastroenterology 2014年第30期20卷 10296-10304页

作者： Ulrich Bork Robert Grützmann Nuh N Rahbari Sebastian Schlch Marius Distler Christoph Reissfelder Moritz Koch Jürgen Weitz Department of GI Thoracic and Vascular SurgeryUniversity Hospital DresdenTU Dresden01307 DresdenGermany

Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on *** residual disease plays a major role in disease relapse and formation of metastases in *** of circulating tumor cells(CTC)in the blood is increasingly used in clinical practice for disease monitoring of CRC *** this review article the role of CTC,disseminated tumor cells(DTC)in the bone marrow and micrometastases and isolated tumor cells(ITC)in the lymph nodes will be discussed,including literature published until September *** disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood,DTC in the bone marrow and/or micrometastases and ITC in the lymph *** residual disease could be used in the future to identify patient groups at risk,who might benefit from individualized treatment options.

关键词： Colorectal cancer Circulating tumor cells disseminated tumor cells Isolated tumor cells Micrometastases Occult disease Minimal residual disease

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Phase I Dose Escalation Study with the Lewis Y Carbohydrate Specific Humanized Antibody IGN311

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Journal of Cancer Therapy 2011年第5期2卷 760-771页

作者： Daniel Oruzio Gunter Waxenecker Christoph Aulmann Bruno Markl Theodor Wagner Geert Mudde Manfred Schuster Norbert Eller Andrea Mayer Stefan Stranner Gottfried Himmler Hans Loibner Günter Schlimok Ralf Kircheis Andreas Nechansky Zentralklinikum AugsburgGermany Igeneon ViennaAustria AGES Pharmed ViennaAustria S-TARget ViennaAustria Apeiron ViennaAustria CDMS ViennaAustria Immatics TubingenGermany f-Star ViennaAustria ViroLogik ErlangenGermany Meridian Biopharmaceuticals ViennaAustria.

Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.

关键词： Passive Immunotherapy Therapeutic Monoclonal Antibody disseminated tumor cells Phase I Study Lewis Y Carbohydrate HAHA (Human Anti-Human Antibodies)

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