Treatment of liver metastases, an update on the possibilities and results

Ruers, Theo J.M.; Bleichrodt, Robert P.

doi:10.1016/s0959-8049(02)00059-x

Cited by 222 publications

(194 citation statements)

References 84 publications

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“…In situ tumour destruction with cryo, radiofrequency or laser ablation has received increasing attention as a treatment modality for focal cancer (Ruers et al, 2001;Ruers and Bleichrodt, 2002;Curley, 2003;Erce and Parks, 2003;Veth et al, 2005). However, little is known regarding the induction of immune responses after in situ tumour destruction or the fate of the generated tumour debris.…”

Section: Discussionmentioning

confidence: 99%

“…Dendritic cells appeared to play an important role in the initiation of this immune response. Tumour ablative treatments, like cryo or radiofrequency ablation, are successfully used in clinical settings to destruct different types of tumours (Zagoria et al, 2001;Ruers and Bleichrodt, 2002;Curley, 2003;Garcea et al, 2003;Raj et al, 2003). Nevertheless, cancer patients treated with ablative regimens mostly develop systemic recurrences as a consequence of the outgrowth of distant micro-metastases, implying that in general no protective immune response is induced.…”

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confidence: 99%

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Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

et al. 2006

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Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory Tcell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-g upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, 'in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

et al. 2006

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“…The high mortality rate of CRC may be due to its high propensity for recurrence and metastasis (5). The liver is the most frequent site of CRC metastasis and ~50% of patients with CRC in China are diagnosed with liver metastases, either in the initial diagnosis or following primary tumor surgery, which makes treatment difficult (6,7). Identification of the cytokines regulating the proliferation and metastasis of CRC is required to understand the nature of CRC.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal transition and metastasis of colorectal cancer cells

et al. 2017

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Abstract. RAS protein activator like 2 (RASAL2) is a RAS-GTPase-activating protein and has recently been identified to be a tumor suppressor in various types of human cancer; however, the function of RASAL2 in colorectal carcinoma (CRC) remains unclear. In the present study, the function of RASAL2 in CRC cells was investigated using a RASAL2 loss-of-function cell model. RASAL2 short hairpin RNA was transfected into the human CRC cell lines LoVo, SW620 and HCT116, and the wild-type colon cell line NCM460. The subsequent downregulation of RASAL2 was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction analyses. It was observed that RASAL2 expression was significantly decreased in human CRC tissues and cell lines (P<0.01). In the loss-of-function cell models, RASAL2 expression was decreased significantly, while cell proliferation, colony formation, migration and invasion were increased (all P<0.01). These effects were associated with the induction of epithelial-mesenchymal transition and Raf/mitogen-activated protein kinase hyperactivation. The results of the present study indicate that RASAL2 is a potential therapeutic target to inhibit CRC progression and metastasis.

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“…Median survival of untreated colorectal liver metastases is approximately 9 months with few survivors beyond 2 years (Bengtsson et al, 1981;Fujimoto et al, 1985;Giacchi et al, 1988;Daly et al, 1989). The reported 5-year survival following surgical resection of liver metastases is between 35 and 40% (Scheele et al, 1990;Ballantyne and Quin, 1993;Leow et al, 1997;Beard et al, 2000;Bolton and Fuhrman, 2000;Ruiz et al, 2000;Weber et al, 2000;Yamaguchi et al, 2000;Ruers and Bleichrodt, 2002).…”

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confidence: 99%

Intensive follow-up after liver resection for colorectal liver metastases: results of combined serial tumour marker estimations and computed tomography of the chest and abdomen – a prospective study

2006

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The aim of the study was to prospectively evaluate an intensive follow-up programme using serial tumour marker estimations and contrast-enhanced computed tomography (CT) of the chest and abdomen in patients undergoing potentially curative resection of colorectal liver metastases. Seventy-six consecutive patients having undergone potentially curative resections of colorectal liver metastases in a single unit were followed up with a protocol of 3 monthly carcinoembryonic antigen and carbohydrate antigen 19-9 estimations and contrast-enhanced spiral CT of the chest, abdomen and pelvis for the first 2 years following surgery and 6 monthly thereafter. The median period of follow-up was 24 months (range 18 -60). Recurrent tumour was classed as early if within 6 months of liver resection. Thirty-seven of the 76 patients (49%) developed recurrence on follow-up. Nineteen recurrences were in the liver alone (51%), 16 liver and extrahepatic (43%) and two extrahepatic alone (6%). Of the 19 patients with isolated liver recurrence, eight developed within 6 months of liver resection none of which were resectable. Of the 11 recurrences after 6 months, five (45%) were resectable. Of the 37 recurrences, CT indicated recurrence despite normal tumour markers in 19 patients. Tumour markers suggested recurrence before imaging in 12 and concurrently with imaging in 6. In the 12 patients who presented with elevated tumour markers before imaging, there was a median lag period of 3 months (range 1 -21) in recurrence being detected on further serial imaging. Seventeen patients who developed recurrence had normal tumour markers before initial resection of their liver metastases. Of these 17, 10 (58%) had an elevation of tumour markers associated with recurrence. Over a median follow-up of 2 years following liver resection, the use of CT or tumour markers alone would have failed to demonstrate early recurrence in 12 and 18 patients respectively. A combination of tumour markers and CT detected significantly more (Po0.05) recurrence than either modality alone. Tumour markers and CT should be used in combination in the follow-up of patients with resected colorectal liver metatases, including patients whose markers are normal at the time of initial liver resection.

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Treatment of liver metastases, an update on the possibilities and results

Cited by 222 publications

References 84 publications

Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal transition and metastasis of colorectal cancer cells

Intensive follow-up after liver resection for colorectal liver metastases: results of combined serial tumour marker estimations and computed tomography of the chest and abdomen – a prospective study

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