New insights into tumor-host interactions in lymphoma metastasis

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual cross-talks) of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.Abbreviations APC Antigen-presenting cells - hCRP Human C-reactive protein - ICAM Intercellular adhesion molecule - IFN Interferon - IL Interleukin - iNOS Inducible NO synthase - LFA Leukocyte function associated antigen - SER Sheep erythrocyte receptor - TA Tumor-associated rejection antigens - TNF Tumor necrosis factor - VCAM Vascular cell adhesion molecule - VLA Very late activated antigen     

细胞粘附分子与肿瘤的侵袭转移

细胞粘附分子是一类跨膜糖蛋白、与肿瘤侵袭转移关系密切。本文概述了细胞粘附分子的种类以及它们与肿瘤侵袭转移的关系。对阐明肿瘤转移机制、评价肿瘤患者转移能力以及评价患者预后具有重要意义。     

改进原位接种技术建立裸小鼠人大肠癌（SW1116）模型

为改进裸小鼠肠原位肿瘤接种方法和提高肿瘤转移发生,用自上肿瘤肠避粘接和脾切除技术,在裸小鼠体内筛选并建立稳定的,有转移能力的模型要现,对裸小以下接种后生长的无转移移能力的人ＳＷ１１１６大肠癌组织块进行大部切除,可诱发肿瘤转移,用肿瘤肠壁原位粘接技术可获得肿瘤的自发转移个别,同时合作脾切除技术更可获得肿瘤的高转移。结果提示,人大肠癌的转移可在裸小本仙诱导增强肿瘤肠壁原位 妆及脾切除是研究建立人大肠主     

CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation

Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4–v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a metastogene may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.Abbreviations CD44s CD44 standard isoform - CD44v CD44 variant isoforms - HA Hyaluronate     

Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement

Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases, including a rare large bone-forming retroperitoneal metastasis, is described. Despite the extensive extrapulmonary metastases, the patient did not develop pulmonary metastases in the 4 years following initial presentation of the primary tumour. Received: 16 December 1998 Revision requested: 14 January 1999 Revision received: 30 July 1999 Accepted: 1 August 1999     

Follow-up of musculoskeletal tumours 2. Metastatic disease

Both the prognosis and the morbidity of a patient with a primary malignant musculoskeletal tumour have improved over the past 25 years due to the advent of adjuvant chemotherapy and limb-sparing surgery. This has important implications for the role of imaging at the time of initial diagnosis and during follow-up. This pictorial essay reviews the imaging and pitfalls in the interpretation of musculoskeletal sarcoma metastases using a variety of radiological techniques. The optimal imaging strategy will be stressed. Received: 29 January 1998; Revision received: 13 May 1998; Accepted: 14 May 1998     

甲状腺癌的颈淋巴结转移与血行转移

目的 探讨甲状腺颈淋巴结转移及血行转移的有关因素,提高甲状腺癌的诊断及治疗水平。方法 对１９８４年１月￣１９９２年１２月收治的２２５例甲状腺癌患者的临床特点、治疗方法及病理结果进行了回顾性分析总结。结果 甲状腺癌的淋巴结及血行转移主要现理类型和肿瘤局部浸润程度有关。乳头状癌、鳞状细胞癌主要表现为区域淋巴结转移,转移率分别为４４．７％、３／３,晚期出现血行转移。滤泡状腺癌虽然分化较好,但多表现有血行     

nm23基因在大肠癌组织中的表达及临床意义

目的研究nm23基因在大肠癌组织中的表达及临床意义。方法用免疫组化方法对63例大肠癌患者骨髓内转移癌细胞及肿瘤组织内nm23表达进行了测定。结果骨髓内转移癌细胞阳性者原发灶nm23蛋白表达率53．1％,低于骨髓内转移癌细胞阴性者的表达率77．4％,有统计学差别（P＜0．05）。发生肝、肾及腹腔广泛转移者原发灶表达率50．0％,低于未发生转移者的表达率81．8％（P＜0．05）。nm23蛋白表达与淋巴结转移无显著相关性。结论nm23蛋白表达与远处转移及骨髓内转移癌细胞呈负相关性,可作为预测转移和判断预后的标志物。     

Heat shock protein 27 overexpression in breast cancer lymph node metastasis

Background: Heat shock protein 27 (hsp-27) is overexpressed in 67% pure ductal carcinoma in situ (DCIS), in 50% DCIS associated with invasive ductal carcinoma (IDC), and in 25% IDC alone. If this decrease in hsp-27 expression has a role in the progression of malignancy in IDC, we postulate a further reduction in expression in nodal metastasis. Methods: To test this hypothesis, we evaluated the distribution of hsp-27 in primary IDC and in synchronous regional lymph node metastasis within the same patient by immunohistochemistry. Results: Nine of 30 primary IDCs (30%) and 22 of 30 lymph node metastases (73%) overexpressed hsp-27. Contrary to our hypothesis, of 21 IDCs with no or low hsp-27 expression, 13 (62%) had overexpression of this protein within nodal metastasis. Conclusions: hsp-27 appears to confer cytoprotection for metastatic cells, which may help explain why hsp-27 overexpression is associated with reduced disease-free survival in breast carcinomas.     

Multidisciplinary management of metastatic colorectal cancer

When colorectal cancer metastasizes to distant organs, usually multiple sites are involved and treatment consists primarily of systemic chemotherapy and supportive care. Chemotherapeutic agents effective against metastatic colorectal cancer include 5-fluorouracil, often used in combination with leucovorin or methotrexate, and irinotecan (CPT-11). Median survival with optimal chemotherapy regimens ranges from 10 to 15 months. Less frequently, colorectal cancer metastasizes only to the liver or lung. In a minority of these cases, surgical resection can be performed and results in a median survival of 28-46 months for hepatic resections and 24-25 months for pulmonary resections. Five-year survival rates range from 24 to 38% and 21 to 44% for hepatic and pulmonary resections, respectively. For isolated liver metastases that are not surgically resectable, other regional therapies that can be considered are hepatic cryosurgery, radiofrequency ablation, and hepatic arterial infusion chemotherapy. Median survival following cryosurgery is between 26 and 30 months, while median survival following radiofrequency ablation has not been established in large series. Hepatic arterial infusion chemotherapy, especially with newer combination drug regimens, may increase survival in patients with isolated liver metastases compared to systemic chemotherapy, but this must be confirmed in randomized, prospective trials. Colorectal cancer metastases to the brain can be treated with radiation therapy or surgical resection, but median survival with treatment is less than one year.