Study of orthotopic transplantation model of human gastrointestinal cancerand detection of micrometastases

AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used forrepetitive investigations and may improve our understanding of carcinogenesis and cancer metastasis.METHODS Intact tissue of human colorectal and pancreatic cancers was transplanted in nude mice. Thebiological characteristics of the original and corresponding transplanted tumors were investigated by HEstaining, PAS staining and immunostaining. The metastases in livers and lungs of the nude mice wereinvestigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers.RESULTS Nine of 16 surgical specimens grew in the nude mice subcutaneously and/or orthotopically (4 of6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissuespecimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cell content, transplantation rate was 100% (3 cases of pancreatic cancerand 3 cases of colorectal cancer). The orthotopically transplanted tumors resembled the original tumormorphologically and biologically, including TAA expression such as CEA by immunohistochemistry, andCEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, were associated with the potential of tumor growth in nude mice. Micrometastases in the lungs andlivers of tumor bearing mice could be detected by immunostaining with biotinylated mab KL-1 and CK20-sepcific RT-PCR.CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude micehas been established. The sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCRwere also established to study xenotransplanted human cancer and its metastatic cancer cells in the liver andlung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and indeveloping new diagnostic methods and therapeutic strategies for metastases.Acknowledgement The authors thank Dr. J. Luettges, Department of Pathology; Kiel University, for investigating thepathological characterics of the specimens; Dr. N. Zawazawa, Institute of Immunology, Kiel University, for the quantitativemeasurement of serum of CEA.     

人胰腺癌细胞株PANC1裸鼠原位模型的建立及磁共振监测

目的 建立一种稳定的人胰腺癌裸小鼠原位移植瘤模型,并探讨无创的磁共振(MRI)对其监测的应用价值.方法 人胰腺癌细胞株PANC1体外常规传代后建立裸鼠皮下种植瘤模型,将皮下种植瘤制成细胞悬液,植入20只BALB/C-nn裸鼠的胰腺包膜下构建人胰腺癌原位移植模型;通过MRI检查监测模型的成瘤率、成瘤时间、肿瘤生长速度、肿瘤形态、信号变化等特征,于第7周末取肿瘤组织行病理学检查.结果 接种后15 d,7只(35%)荷瘤鼠在MRI上显示成瘤,至接种后27 d,成瘤率为100%.肿瘤信号与邻近组织相比,90%(18/20)病灶T1WI呈均匀稍低信号,10%(2/20)呈等信号;75%(15/20)在T2WI呈均匀高信号.移植后2、3、4、5、6、7周经MRI测量的移植瘤体积分别为(12.6±2.4)mm3、(94.3±11.2)mm3、(175.9±82.5)mm3、(395.8±126.6)mm3、(1290.2±167.2)mm3、(1583.4±87.4)mm3.病理学检查确诊为胰腺低分化腺癌,并保持原发瘤的生物学特征.结论 人胰腺癌细胞株PANC1移植瘤制成的细胞悬液种植裸小鼠胰腺包膜下制备胰腺癌模型符合人胰腺癌的特征,且易于无创监测,为临床研究提供了一个有效、稳定的体内实验体系.     

Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors

The development of drugs for the control of tumor angiogenesis requires a simple, accurate, and economical assay for tumor-induced vascularization. We have adapted the orthotopic implantation model to angiogenesis measurement by using human tumors labeled with Aequorea victoria green fluorescent protein for grafting into nude mice. The nonluminous induced capillaries are clearly visible against the very bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. The orthotopic implantation model of human cancer has been well characterized, and fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. Intravital images of orthotopically implanted human pancreatic tumors clearly show angiogenic capillaries at both primary and metastatic sites. A quantitative time course of angiogenesis was determined for an orthotopically growing human prostate tumor periodically imaged intravitally in a single nude mouse over a 19-day period. Whole-body optical imaging of tumor angiogenesis was demonstrated by injecting fluorescent Lewis lung carcinoma cells into the s.c. site of the footpad of nude mice. The footpad is relatively transparent, with comparatively few resident blood vessels, allowing quantitative imaging of tumor angiogenesis in the intact animal. Capillary density increased linearly over a 10-day period as determined by whole-body imaging. Similarly, the green fluorescent protein-expressing human breast tumor MDA-MB-435 was orthotopically transplanted to the mouse fat pad, where whole-body optical imaging showed that blood vessel density increased linearly over a 20-week period. These powerful and clinically relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological microenvironments.     

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristic

AIM To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after screening from 34 colorectal carcinomas. They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis. CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.INTRUDUCTIONSome models of nude mice that fresh human colorectal carcinoma tissue or cells were successfully transplanted subcuteneously have been reported at home and abroad[1,2]. But until now there has been no report on a liver metastasis model of human colorectal carcinoma established by orthotopic transplantation in nude mice in China. Based on our previous models of human liver and pancreas carcinoma by orthotopic transplantation[3,4], we established liver metastasis models of colon and rectum carcinoma with a spontaneous metastasis rate of 100%.     

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

ＩＮＴＲＵＤＵＣＴＩＯＮＳｏｍｅｍｏｄｅｌｓｏｆｎｕｄｅｍｉｃｅｔｈａｔｆｒｅｓｈｈｕｍａｎｃｏｌｏｒｅｃｔａｌｃａｒｃｉｎｏｍａｔｉｓｕｅｏｒｃｅｌｓｗｅｒｅｓｕｃｃｅｓｆｕｌｙｔｒａｎｓｐｌａｎｔｅｄｓｕｂｃｕｔｅｎｅｏｕｓｌｙｈａｖｅｂｅｅｎｒ...     

微囊化人胰腺癌细胞建立裸鼠胰腺癌模型研究

目的研究微囊化人胰腺癌细胞建立裸鼠胰腺癌模型效果,以期建立稳定的更为理想的胰腺癌动物模型.方法 分别以人胰腺癌细胞悬液和微囊化人胰腺癌细胞悬液建立皮下移植瘤模型,定期监测皮下肿瘤大小,绘制生长曲线并进行比较.分别以人胰腺癌细胞悬液和微囊化人胰腺癌细胞建立原位移植瘤模型,分别于模型建立后第4周和第8周进行正电子发射计算机...     

Study on the anticarcinogenic effect and acutetoxicity of livertargeting mitoxantronenanoparticles

ＩＮＴＲＯＤＵＣＴＩＯＮＤＨＡＱｉｓａｎｅｗｓｙｎｔｈｅｔｉｃａｎｔｉｔｕｍｏｒａｇｅｎｔ,ｅｆｆｅｃｔｉｖｅｉｎｍａｎｙｃａｎｃｅｒｓ,ｅｓｐｅｃｉａｌｌｙｉｎｈｅｐａｔｉｃｃａｎｃｅｒ,ａｐｒｉｎｃｉｐａｌｃａｎｃｅｒｏｆｈｉｇｈｉｎｃｉｄｅｎｃｅａｎｄｍｏｒｔａｌｉｔｙ［１］．Ｎａｎｏｐａｒｔｉｃｌｅｓ（ＮＰ）ｉｓａｎｅｗｄｒｕｇｃａｒｒｉｅｒ［３］ｓｈｏｗｉｎｇａｄｉｓｔｉｎｇｕｉｓｈｅｄｌｉｖｅｒｔａｒｇｅｔｉｎｇａｂｉｌｉｔｙ,ｔｈｅｒｅｆｏｒｅ,ＮＰｌｏａｄｉｎｇｗｉｔｈａｎｔｉｈ…     

Studies on effect of carcinoembryonic antigen on leucocyte migration inhibition test in patients with colorectal cancer

Leucocyte migration inhibition test (LMIT) is a useful method to detect tumor associated antigens (TAA) in cancer patients. Carcinoembryonic antigen (CEA) is one of the best tumor markers for gastrointestinal cancer, and especially for colorectal cancer patients, who show high plasma CEA level frequently. In this study, we performed LMIT in 71 colorectal cancer patients with 3 M KCl extracts of cancer tissues and measured concentration of CEA in the plasma and the extracts of cancer tissue simultaneously. Although CEA in colorectal cancer extracts was individually varied from low to high in concentration, the levels of CEA had no relation to LMI reactivity. In addition, the LMI reactivity of colorectal cancer patients did not relate to the plasma CEA level of the corresponding patient. The results suggest that some antigens which induce leucocyte migration inhibition factor (LMIF) to lymphocytes from colorectal cancer patients might be different substances from CEA.     

rmhTNF对人胃癌细胞株裸鼠移植瘤模型的治疗作用

背景:重组改构人肿瘤坏死因子(rmhTNF)是原型TNF-α的改构体,前期实验显示其对体外培养的人胃癌细胞株具有抑制增殖和诱导凋亡作用。目的:初步研究rmhTNF对人胃癌细胞株裸鼠移植瘤模型的治疗作用。方法:雄性BALB/c裸鼠皮下接种人胃癌细胞株BGC-823构建移植瘤模型,随机予rmhTNF、TNF-α,5-氟尿嘧啶(阳性对照)和0.9%NaCl溶液(阴性对照)进行干预,观察各组裸鼠一般情况、移植瘤生长情况及其组织病理学改变。结果:建模裸鼠成瘤率为100%。各药物干预组移植瘤生长均明显减慢,其中rmhTNF组生长抑制最为明显,生长曲线较阴性对照组明显下移,抑瘤率显著高于TNF-α组和阳性对照组(83.1%对59.8%和50.1%,P0.01),一般情况与接种前相比无明显改变,移植瘤组织中可见较多凋亡和坏死细胞。结论:BGC-823细胞在BALB/c裸鼠皮下有良好的成瘤性。rmhTNF在体内能直接诱导胃癌细胞凋亡和坏死,对人胃癌细胞株裸鼠移植瘤模型具有治疗作用。     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

AIM To study the phase cancer tissue intercellular adhesion molecule-1 (ICAM-1) expression of human cancer metastasis model in nude mice, and to analyze the relationship between ICAM-1 expression and the metastasis and recurrence of hepatocellular cancinoma (HCC).METHODS HCC tissues from liver cancer metastasis model in nude mice (LCI-D20) was orthotopically implanted, and ICAM-1 expression in HCC tissues at different growing time were detected by immunodot blot. Tumor size, intrahepatic and extrahepatic metastasis foci were observed by naked eyes and under light microscope.RESULTS ICAM-1 was positively correlated to the tumor growing time (r=0.88, P＜0.01) and tumor size r=0.5, P＜0.05). It was higher in metastatic HCC than in nonmetastatic HCC (8.24±0.95 vs 3.03±0.51, P＜0.01). ICAM-1 content in cancer tissues increased suddenly after metastasis occurred and then maintained in a high level. ICAM-1 was also higher in multimetastasis group than in monometastasis group (10.05±1.17 vs 5.48±0.49, P＜0.05).CONCLUSION Tissue ICAM-1 could predict not only the metastasis of human liver cancer metastasis model in nude mice early and sensitively, but also the metastasis degree. So tissue ICAM-1 may be a potential index indicating the status of metastasis of HCC patients.     

Growth inhibition of liver metastases by the anti‐angiogenic drug TNP‐470

Abstract: Objective: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP‐470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. Background: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP‐470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti‐angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. Methods: 10⁷ DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP‐470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti‐von Willebrand Factor monoclonal antibody. Results:In vitro, TNP‐470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC₅₀ of 0.1 μg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm³ vs 406 mm³, p=0.03) were significantly reduced in the TNP‐470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/×200 field, p=0.41). Conclusion: TNP‐470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti‐angiogenic and direct cytotoxic effects.     

Impact of p27mt gene on transplantation model of human colorectal cancer in nude mice

AIM： To investigate the inhibitory and anti-metastatic effect of mutant p27 gene （p27mt） on the growth of colorectal cancer xenografts in nude mice and its underlying mechanism. METHODS： Inhibitory effect of p27mt gene on the growth of colorectal cancer xenografts was determined by measurement of tumor size before and after direct intra-tumoral injection of Ad-p27mt in a pre-established transplantation model of human colorectal cancer in nude mice. Cell cycle and apoptosis were detected by flow cytometry performed on single-cell suspension from an isolated tumor. Expression of MMP-9 in tumor tissue was detected by immunohistochemistry. RESULTS： The average sizes of transplantation tumors were 1.94 ± 0.67 cm^3, 2.75 ± 0.83 cm^3 and 3.01 ± 0.76 cm^3 in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.05）. The average proliferation rates were 37.34% ± 1.45%, 53.16% ± 3.27% and 54.48% ± 2.43%, in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.05）. The average apoptosis rates were 19.79% ± 3.32%, 6.38% ± 4.91% and 7.25% ± 5.20% in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.01）. The average MMP-9 expression rates were 20%, 75% and 66.7% in the Ad-p27mt, Ad-LacZ and control groups, respectively （P 〈 0.01）. CONCLUSION： p27mt inhibits the growth of transplanted tumor by blocking the proliferation of cancer xenografts and by promoting apoptosis of transplantated tumor cells, as well as decrease transplanted tumor metastasis.     

人胃癌裸鼠原位移植模型的生物学行为研究

目的建立人胃癌裸鼠胃壁原位移植瘤模型，并与相应的皮下移植瘤作比较，以探讨宿主器官微环境对胃癌细胞浸润及转移等生物学行为的影响．方法将人胃癌细胞系ＭＧｃ８０３及其克隆株Ｃ１１癌细胞分别接种于裸鼠胃壁及背部皮下，比较原位和皮下移植瘤的成瘤率、生长率、生长方式及浸润、转移等生物学行为，以及体外回复培养后瘤细胞的增殖能力．结果胃壁原位及皮下移植瘤体内成瘤率、生长率及形态学上均无明显不同；其体外增殖能力也无显著性差异．但皮下移植瘤多呈局限性生长，无肝、脾、肾转移，其转移仅限于肺及个别局部淋巴结．胃壁原位移植瘤则浸润破坏胃壁各层组织结构，并直接蔓延到邻近各器官组织．其转移既有经血道至肝、肺、脾、肾等部位，也有经淋巴道至多数局部及远处淋巴结，其淋巴结的转移率较皮下移植瘤有显著增高（Ｐ＜００５）；且多伴有腹、盆腔内广泛种植性转移．结论裸鼠胃壁微环境较皮下组织更适合于人胃癌ＭＧｃ８０３及Ｃ１１移植瘤的浸润及转移的表达，该原位移植瘤模型的恶性生物学行为更接近临床胃癌患者的体内侵袭及转移的实际．     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

Ｐｈａｓｅｔｉｓｓｕｅｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ１ｅｘｐｒｅｓｓｉｏｎｉｎｎｕｄｅｍｉｃｅｈｕｍａｎｌｉｖｅｒｃａｎｃｅｒｍｅｔａｓｔａｓｉｓｍｏｄｅｌＳＵＮＪｉｎｇＪｉｎｇ,ＺＨＯＵＸｉｎＤａ,ＬＩＵＹｉｎＫ...     

鼠移植性肝癌内注射乙酸的治疗实验

目的观察３００ｍＬ／Ｌ乙酸局部注射治疗裸鼠移植瘤的效果,并探讨其作用机制．方法应用人肝癌（ｈＨＣＣ）细胞悬液接种于Ｂａｌｂ／ｃｎｕ／ｎｕ裸鼠皮下建立移植瘤模型共１２只,分为３组,乙酸组５只注射３００ｍＬ／Ｌ乙酸０１５ｍＬ,乙醇组５只注射无水乙醇０１５ｍＬ,盐水组２只注射生理盐水０１５ｍＬ,２次／ｗｋ,共４次．观察移植瘤生长情况．结果乙酸组移植瘤全部结痂、脱落,而乙醇组除一只裸鼠移植瘤结痂、脱落外其余均明显缩小（Ｐ＜００５）,盐水组移植瘤呈结节样进行性生长．病理学检查：乙酸组可见纤维组织未见肝癌细胞,乙醇组除大片组织坏死外可见散在的肝癌细胞团,盐水组肝癌细胞生长良好．结论３００ｍＬ／Ｌ乙酸较无水乙醇能产生更广泛的组织坏死,可以代替无水乙醇局部注射治疗ｈＨＣＣ．     

Newly established human pancreatic carcinoma cell lines and their lectin binding properties

Summary Two human pancreatic carcinoma cell lines, designated HuP-T3 and HuP-T4, were established from the ascites of pancreatic cancer patients with carcinomatous peritonitis. The cell lines were grown in monolayer cultures and had population doubling times of 38.6 and 37.1 h, respectively. HuP-T4 secreted large amounts of CEA and CA19-9 into the medium, and HuP-T3 produced a small amount of CEA, but no CA19-9. Both cell lines showed tumorigenicity in nude mice. Histologically, the HuP-T3-derived tumor was poorly differentiated adenocarcinoma, and the HuP-T4-derived tumor was well differentiated papilotubular adenocarcinoma. In lectin histochemistry at both light and electron microscopic levels, the most striking difference between the lectin binding properties of the two cell lines and those of control normal pancreatic ductal cells was that soybean agglutinin (SBA) bound to both cell lines, but not to controls. These newly established cell lines should be useful models that will contribute to clarifying the biological and biochemical characteristics of pancreatic cancer.     

VEGFR-3小干扰RNA对结肠癌裸鼠移植瘤生长的影响

目的:研究血管内皮生长因子受体3(vascularendothelial growth factor receptor 3,VEGFR-3)小干扰RNA对结肠癌细胞移植瘤模型生长的影响.方法:构建VEGFR-3小干扰RNA表达载体.将结肠癌LoVo细胞注射入裸鼠皮下建造裸鼠移植瘤模型.将15只裸鼠结肠癌模型随机分成3组:实验组(pG-siRNA/VEGFR-3重组质粒)、阴性对照组(pG-HK重组质粒)与空白对照组.分别瘤体内注射相应的siRNA混合物或转染剂混合液,每3 d注射1次,共注射3次,观察肿瘤体积的变化;6 wk后处死裸鼠,肿瘤称取质量,并进行qRT-PCR和Western blot测定VEGFR-3 mRNA和蛋白的变化,通过免疫组织化学进行微淋巴管计数.结果:实验组移植瘤体积和质量明显小于阴性对照组和空白对照组,有显著的统计学意义(P<0.001).实验组抑制率为52.75%,与对照组相比,差异有显著(P<0.001).qRT-PCR和Western blot测定VEGFR-3 mRNA和蛋白的变化比较,实验组有明显降低(P<0.001).实验组淋巴管计数较对照组差异显著(P<0.05).结论:VEGFR-3 siRNA可以抑制裸鼠结肠癌细胞移植瘤的生长,并减少裸鼠移植瘤淋巴管生成,能有效抑制结肠癌细胞的生长.     

Establishment of alpha-fetoprotein producing human rectal cancer cell line (RKK-YK) and its features]

We succeeded in establishing a rectal cancer cell line RKK-YK from the primary lesion in a patient with rectal cancer. It took 36.2 hours for duplication. We were able to transplant the RKK-YK cell line to nude mice at a transplantation rate of 50%. The transplanted tumor exhibited histological features similar to those of the primary lesion. Cancer cells with two different degrees of differentiation, in which features of moderately differentiated adenocarcinoma and well-differentiated adenocarcinoma were observed together, were established. The levels of the tumor markers (CEA, CA19-9 and AFP) were elevated in the supernatant of the culture solution and the serum of the nude mice over time course. In the immunohistological examination of the transplanted tumor, anti-CEA, anti-CA19-9 and anti-AFP antibodies were positively stained. Molecular biological analysis revealed nor point mutation or deletion in K-ras gene exon 1 and 2, p53 gene exon 5 to 11 or MCC.     

A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.

Pancreatic cancer is one of the most intractable and least understood of all human cancers. Pancreatic cancers is the fourth-leading cause of cancer-related mortality in the United States with less than 2% of the patients surviving for 5 yr. In an effort to help develop more effective treatment modalities for pancreatic cancer and improve detection, we report an animal model for individual human pancreatic-cancer patients. The model involves orthotopic transplantation of histologically intact pancreatic-cancer specimens to the nude-mouse pancreas, which can result in models that resemble the clinical picture including (i) extensive local tumor growth, (ii) extension of the locally growing human pancreatic cancer to the nude-mouse stomach and duodenum, (iii) metastases of the human pancreatic tumor to the nude-mouse liver and regional lymph nodes, and (iv) distant metastases of the human pancreatic tumor to the nude-mouse adrenal gland, diaphragm, and mediastinal lymph nodes. In a series of five patient cases, a 100% take rate has been demonstrated, and of 17 mice transplanted, 15 supported tumor growth. Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens, such as tumor-associated glycoprotein 72 and carcinoembryonic antigen in the transplanted tumors when compared with the original surgical biopsy, suggesting similarity between the two. This model should, therefore, prove valuable for treatment evaluation of individual cancer patients, as well as for evaluation of experimental treatment modalities for this disease.