Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and¹¹¹In-labelling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma. Offrint requests to: E. Schdfer     

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111In-labeling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.     

Scintigraphy with In-111 labeled lymphokine-activated killer cells of malignant brain tumor

This study was undertaken to assess the in vivo distribution and migration of lymphokine-activated killer (LAK) cells to the target malignant foci in four patients with advanced malignant brain tumor. All four patients had failed to respond to prior adoptive immunotherapy. After the intravenous administration of radiolabeled LAK cells, most of the radiolabeled cells were distributed in the liver and spleen, with lesser radioactivity in the lung and bone marrow. Scintigraphy revealed the target malignant foci in all four patients to be areas of increased radioactivity. The number of radiolabeled LAK cells that accumulated in the intracranial malignant lesions, however, seemed to be insufficient to mediate regression of the solid tumor mass by direct cell-to-cell interaction. We conclude that the failure of adoptive immunotherapy could be accounted for by the poor migration of infused LAK cells to the target malignant foci. We also conclude that radionuclide study with radiolabeled lymphokine-activated culture cells against tumors is likely to be helpful as a means to investigate effective possibilities for subsequent adoptive immunotherapy.     

肺空洞型转移瘤CT诊断

目的:分析空洞型肺转移瘤CT表现及形成机制。方法:对26例经证实的空洞型转移瘤病例进行分析。结果:空洞型转移瘤以肺内圆形类圆形结节内合并空洞较多见,可为厚壁或薄壁。结论:CT检查对肺转移瘤的特殊表现(空洞样转移)有较重要价值。     

自体树突细胞联合细胞因子诱导的杀伤细胞治疗转移性肾癌的疗效分析及随访观察

目的 评价自体树突细胞(DC)联合细胞因子诱导的杀伤细胞(CIK)治疗转移性肾癌的临床疗效、免疫功能变化及随访结果.方法 采集27例转移性肾癌患者的外周血单个核细胞(PBMC),经实验室体外培养诱导产生DC和CIK细胞,经无菌检测、流式细胞术表型鉴定及细胞计数后回输给患者.于第7、9、11、13天皮下注射DC,第11、13天静脉回输CIK,每疗程间隔3个月,直至疾病进展,观察临床疗效及免疫功能的变化.结果 27例转移性肾癌患者经DC-CIK治疗后的客观反应率为37％,疾病控制率为85％,2年总生存率为81.5％.与治疗前比较,治疗后患者外周血CD3+CD4+CD8-、CD3+CD4-CD8+、CD3+CD19-、CD3-CD19+、CD3-CD16+CD56+、CD3+CD 16+CD56+、CD3+HLA-DR、CD3+HLA-DR+、CD3+CD28+CD8+细胞亚群及Th2细胞无显著变化(P＞0.05),Th1细胞有升高趋势(P＜0.05),多次治疗后CD3+CD4+CD25+T细胞(即调节性T细胞,Treg细胞)有降低的趋势(P＜0.05).治疗过程中27例患者均未出现明显不良反应.结论 DC-CIK细胞免疫治疗为转移性肾癌患者提供了一种新的安全有效的治疗方法,可改善转移性肾癌患者的免疫抑制状态,提高患者的抗肿瘤免疫反应,无明显不良反应.     

Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma

High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T(2) weighted imaging and T(1) weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T(1) and T(2) weighted CMRI techniques to diagnose IL-2 induced myocarditis.     

树突状细胞与细胞因子诱导的杀伤细胞共培养后对人肝癌细胞株HEP-3杀伤活性的研究

 目的 研究树突状细胞(DC)与细胞因子诱导的杀伤细胞(CIK)共培养后增殖活性、表型的变化和其对人肝癌细胞株HEP-3杀伤活性的影响.方法 分离外周血单个核细胞(PBMC),经不同细胞因子作用后定向分化成DC和CIK细胞,将收获的DC与CIK共培养3d,以流式细胞仪检测CIK 细胞膜表面分子表达,MTT 法检测共培养后CIK细胞对HEP-3杀伤活性的变化.结果 CIK与DC 共培养3d 后增殖活性开始显著提高,与DC共培养的CIK较单独培养的CIK具有更强的杀瘤活性.结论 共培养后DC能够促进CIK增殖,提高其对肝癌细胞的杀伤活性,为指导临床应用DC与CIK联合治疗原发性肝癌提供了实验依据.     

Urographic manifestations of metastatic melanoma

Urinary tract involvement with metastatic malignant melanoma occurs much more commonly than generally thought. It is usually part of a disseminated process with a poor life expectancy. The renal parenchyma is the most common site affected, although this is infrequently detected roentgenographically. Urothelial involvement of the renal pelves, ureters, and bladder manifests as single or multiple filling defects at pyelography. This appearance of metastatic melanoma of the urinary tract has not been previously described in the roentgenologic literature. Recognition is important to prevent unnecessary intervention and to guide palliative treatment.     

颅内转移性恶性黑色素瘤9例临床分析

目的探讨颅内转移性恶性黑色素瘤的临床表现、诊断及手术切除效果。方法回顾性分析我科自2000年1月～2010年1月10年间手术切除的9例颅内转移性恶性黑色素瘤的临床和影像学资料,跟踪随访患者术后疗效。结果 9例患者均可见原发病灶;颅内转移灶中,7例全切,2例大部切除;随访期间所有患者死亡,生存时间最短4个月,最长23个月。结论颅内转移性恶性黑色素瘤恶性程度高,彻底切除颅内病灶可延长患者生存期,但预后仍差。     

Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma

Purpose

We retrospectively evaluated the tumor regression after radiotherapy in combination with the immune checkpoint inhibitor nivolumab for metastatic melanoma.

Materials and methods

We evaluated the extracranial metastatic melanoma lesions to which concomitant radiotherapy with nivolumab was administered from June 2015 to February 2017. Tumor volume and maximum diameter were measured at the time of pre-radiotherapy and best response, and the tumor reduction rate was assessed in two ways that our hospital adopts: tumor volume and diameter.

Results

Seven lesions in five patients were evaluated. The median time from the start of nivolumab treatment to the start of radiotherapy was 5 months (range 0–22 months). The objective response rate was 85.7% in the evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The objective complete response rate was 28.6% in evaluation by tumor volume and 14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year overall survival rate after nivolumab treatment were 75% and 50%, respectively. Two patients who obtained a complete response had presented with vitiligo.

Conclusion

The combination of radiotherapy and nivolumab treatment produced favorable responses. Vitiligo may be correlated with a good response to concomitant radiotherapy with nivolumab.

     

MR imaging of intracranial metastatic melanoma

Ten patients with intracerebral metastases from malignant melanoma were evaluated with magnetic resonance (MR) imaging performed at 1.5 T using spin-echo techniques. On the basis of histopathologic findings in three of 10 cases and CT appearances in all 10 cases, three patterns were identified on analysis of MR signal intensities in both short repetition time/echo time (TR/TE) and long TR/TE spin-echo scans. In comparison to normal cortex, nonhemorrhagic melanotic melanoma appeared markedly hyperintense on short TR/TE images and isointense, mildly hypointense on long TR/TE images. Nonhemorrhagic, amelanotic melanoma appeared isointense or mildly hypointense on short TR/TE and isointense or mildly hyperintense on long TR/TE images. Hemorrhagic melanoma varied in appearance, depending on the stage of hemorrhage. Melanotic, nonhemorrhagic melanoma can be distinguished from early and late subacute hemorrhage by its signal intensity on long TR/TE images. Spin-echo MR appears to be the method of choice for diagnosing melanotic metastases.     

SPECT in gallium imaging in a patient with metastatic melanoma

Gallium imaging may play an important role in both initial evaluation and in follow-up in patients with metastatic melanoma. We present a case where the patient had gallium-avid metastatic melanoma. SPECT proved helpful in the initial evaluation.     

CT halo sign as an imaging marker for response to adoptive cell therapy in metastatic melanoma with pulmonary metastases

Objectives

The halo sign refers to a zone of ground-glass attenuation surrounding a pulmonary nodule. Pulmonary metastatic nodules exhibiting a halo sign are seen mainly in hypervascular tumours. We describe the appearance of a halo sign following treatment of adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) to melanoma patients with lung metastases.

Methods

The study included 29 melanoma patients with pulmonary metastases who received TIL therapy. Pre- and post-treatment chest CTs were retrospectively reviewed for the presence of a halo sign and its correlation with therapeutic response.

Results

A pulmonary halo sign was not seen in any pre-treatment CT. It was observed in four of 12 patients who responded to the therapy but not in those who failed to respond. Significant differences were found between response ratio in patients in whom post-TIL halo sign appeared compared with those without the halo sign (p?=?0.02).

Conclusions

The appearance of a CT halo sign in melanoma with lung metastases following TIL therapy may indicate antitumoral effect and a good response to therapy. Our findings emphasize the importance of applying new assessment criteria for immunological anticancer therapies.

Key Points

? Tumour-infiltrating lymphocytes (TIL) in melanoma patients is a promising novel immunotherapy ? Post-therapy pulmonary halo sign appeared in one-third of TIL responders ? Pulmonary halo sign may serve as an imaging marker for antitumoral activity     

Influence of irradiation on metabolism and metastatic potential of B16-F10 melanoma cells

Purpose:?To analyse short term and long term X-ray irradiation effects on proliferation, viability, glucose and amino acid uptake of murine melanoma cells in vitro and metastasis in vivo.

Materials and methods:?B16-F10 melanoma cells were irradiated with different doses of X-ray irradiation (200?kV) in the range from 1–20?Gy. One, two and three days respectively 7, 14 and 21 days after treatment cells were analysed concerning cell growth, viability, proliferation, cell cycle distribution, glucose and amino acid transport. Moreover the capability of the cells for in vivo metastasis was examined.

Results:?As short term response on irradiation we detected decreased cell growth, viability and arrest in the G2/M phase of the cell cycle. Long term response involves re-start of proliferation, increased cell growth and glucose uptake but still decreased viability and amino acid transport. In vivo metastasis is lost immediately after irradiation and regained to a low extent beyond two weeks time for recurrence of cells before injection.

Conclusions:?In vitro data suggest that surviving melanoma cells compensate the initial irradiation-dependent damage of proliferation within three weeks possibly by increase in glucose uptake. For metastasis in vivo the role of additional mechanisms is strongly suggested.     

硼中子俘获疗法促人黑色素瘤细胞凋亡

目的 研究硼中子俘获疗法(BNCT)体外杀伤人黑色素瘤细胞的效应及机制.方法 首先检测黑色素瘤细胞A375吸收含硼化合物二羟基苯丙氨酸硼(BPA)的情况,然后采用医院中子照射器(IHNI-1)对含硼(10B)细胞进行照射.克隆存活实验检测细胞的放射敏感性,MTT法检测细胞增殖率,流式细胞术检测凋亡,Western blot检测胞质内细胞色素C表达和caspase-9的激活.结果 BPA孵育24 h,A375细胞10B浓度为(2.884±0.148)μg/107个细胞,达到了BNCT杀伤细胞的要求.富含10B的细胞经中子照射2.1 min后存活分数降低为对照组的58％(t=2.964,P＜0.05),细胞经中子照射后24 h增殖率下降为对照组的83％(t=3.286,P＜0.05),BNCT组细胞凋亡率达(55.2±7.9)％,明显高于对照组(t =9.754,P＜0.05),胞质内细胞色素C水平上升且caspase-9激活程度增加(t=7.625、8.307,P＜0.05).结论 BNCT能够杀伤黑色素瘤细胞,其机制可能通过线粒体途径诱导细胞凋亡.