Abstract:
:Radioiodinated N-(2-(diethylamino)ethyl)benzamides have recently been discovered as selective agents for melanotic melanoma and are used for scintigraphic imaging in nuclear medicine. Owing to the high binding capacity, benzamide derivatives conjugated with alkylating cytostatics were synthesized and tested for their potential for targeted drug delivery. Conjugates of chlorambucil with procainamide (1), diethylaminoethylamine (2) and 2-pyrrolidin-1-yl-ethylamine (3), as well as 4-(bis(2-chloroethyl)amino)- (6,7) and 4-(N,N-diethyltriazeno)-substituted (8-10) benzamides, were synthesized. Cell uptake studies with B16 melanoma cells revealed high uptake of radioiodinated 1 and 2, while radiolabelled chlorambucil was found to lack this characteristic. These results were confirmed by biodistribution studies in a mouse melanoma model. Viability measurements revealed that all chlorambucil-benzamide derivatives showed higher toxicity against B16 melanoma and SK-MEL-28 cells than did the parent chlorambucil itself, and that the triazene derivatives were more potent than dacarbazine, which is currently used as a standard cytostatic drug in melanoma therapy. Of all the compounds tested in this series, the triazenes 9 and 10 showed the most promising targeting effect. The toxicity of these compounds against hepatoma cells (MH3924A) and, to a lesser extent, against mouse fibroblast (NIH 3T3) and cervix carcinoma (HeLa) cells was also enhanced, but they were not as toxic as dacarbazine (HeLa). These findings support the concept of a selective, benzamide-mediated in vivo delivery of cytostatics in melanoma cells, leading to enhanced efficacy.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Wolf M,Bauder-Wüst U,Mohammed A,Schönsiegel F,Mier W,Haberkorn U,Eisenhut Mdoi
10.1097/00008390-200410000-00004subject
Has Abstractpub_date
2004-10-01 00:00:00pages
353-60issue
5eissn
0960-8931issn
1473-5636pii
00008390-200410000-00004journal_volume
14pub_type
杂志文章abstract::The mechanism of action of fotemustine, a relatively new chloroethylnitrosourea, was evaluated in human melanoma cells in order to assess its potential as an agent for hyperthermic limb perfusion. Fotemustine was more toxic to O6-alkylguanine methyl transferase (AGT) deficient (Mer-) cells than Mer+ cells, implicating...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199802000-00012
更新日期:1998-02-01 00:00:00
abstract::In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200106000-00013
更新日期:2001-06-01 00:00:00
abstract::Two human melanoma tumour cell lines, one radiation resistant and one radiation sensitive, were studied for their capacity for repair of sublethal radiation damage (SLDR) and for hyperthermia inhibition of radiation damage. The most resistant cell line demonstrated a survival curve with a large shoulder and a large SL...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199406000-00003
更新日期:1994-06-01 00:00:00
abstract::Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progres...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200508000-00002
更新日期:2005-08-01 00:00:00
abstract::Cell free extracts from metastases of human melanoma contain a highly active ribonucleoside diphosphate reductase (RR) which uses guanosine diphosphate (GDP) as substrate and deoxythymidine triphosphate (dTTP) as effector. No activity could be detected in these extracts when cytidine diphosphate (CDP) was used as the ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199212000-00014
更新日期:1992-12-01 00:00:00
abstract::Conditional survival in patients with localized primary cutaneous malignant melanoma (CMM) is well described. However, conditional recurrence-free survival (RFS) has not been investigated before. The aim of this study was to determine conditional RFS and test for time dependency in prognostic factors in patients with ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000479
更新日期:2018-12-01 00:00:00
abstract::Despite the general advances in the chemotherapy of malignancies, progress comes slow in the management of patients with disseminated melanoma. Unreflected enthusiasm and frustrated scepticism are the scylla and charybdis between which the physician tries to choose the right way. ...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::Locally advanced cutaneous melanoma has marked quality-of-life implications; however, the patient experience of symptom management and subsequent impact on quality of life has not been well described. This study aims to address the impact on patients of advanced cutaneous melanoma through qualitative interviews. Adult...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000425
更新日期:2018-04-01 00:00:00
abstract::Sentinel lymph node dissection (SLND) identifies melanoma patients with metastatic disease who would benefit from radical lymph node dissection (RLND). Rarely, patients with melanoma have an underlying lymphoproliferative disease, and melanoma metastases might develop as collision tumours in the sentinel lymph node (S...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000098
更新日期:2014-08-01 00:00:00
abstract::During the initiation and progression of malignant melanoma a series of genetic events accumulate, including alterations of chromosome 11q. Recently, an important tumour suppressor gene, the multiple endocrine neoplasia type 1 (MEN1) gene, has been mapped on 11q13 and has been cloned. To assess whether the MEN1 region...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199906000-00006
更新日期:1999-06-01 00:00:00
abstract::Melanocytes are pigmented cells derived from the neural crest; their proliferation is restrained by immune system. The eruption of nevi after an immunosuppressive condition is a peculiar phenomenon indicating that the immune system may play a major role in limiting proliferation of melanocytes. In this review, we anal...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/CMR.0b013e328322fc20
更新日期:2009-04-01 00:00:00
abstract::Ophthalmological complications constitute a class effect of treatment with BRAF inhibitors. Encorafenib is a new BRAF inhibitor currently being tested in phase 3 clinical trials for advanced or metastatic melanoma as monotherapy or in combination with the MEK-inhibitor binimetinib. In this study, we present a case of ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000505
更新日期:2018-12-01 00:00:00
abstract::The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282f1d2ec
更新日期:2007-12-01 00:00:00
abstract::In several solid tumors, an increased stathmin expression is associated with both poor prognosis and resistance to certain chemotherapy types. However, the data regarding melanocytic lesions are very limited. The goals of our study are as follows: the assessment of stathmin expression in benign and malignant melanocyt...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000550
更新日期:2019-04-01 00:00:00
abstract::The objective of this study was to describe the risk factor profile of skin cancer screening participants and to determine whether there is an association between the number of skin cancer/melanoma risk factors and the likelihood of diagnosis of a malignant melanoma. Seventy skin cancer screening clinics were held by ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000205023.02527.ab
更新日期:2006-08-01 00:00:00
abstract::Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies. The most concerning side effects reported in clinical studies of ipilimumab fall into the category of immune-re...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835c7e68
更新日期:2013-02-01 00:00:00
abstract::Several comparative genomic hybridization studies provide evidence for overrepresentation of the long arm of chromosome 20 in malignant melanoma. These studies also suggest that chromosome 20q contains genes that may contribute to melanoma pathogenesis. To refine the region of 20q amplification and to identify potenti...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3280141617
更新日期:2007-02-01 00:00:00
abstract::Melanoma tumors have been shown to comprise both invasive and proliferative cell subpopulations. These populations are highly plastic, thus hampering full characterization and therapeutic targeting of dormant and partially dedifferentiated invasive cells. We have reported, previously, that melanoma cells grown in a se...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328351e7c4
更新日期:2012-06-01 00:00:00
abstract::We have observed that an early increase in the CD4+/CD8+ ratio of metastatic melanoma patients during chemoimmunotherapy is the most favourable independent prognostic factor. In this study, 87 patients with metastatic melanoma were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) before and during che...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200412000-00009
更新日期:2004-12-01 00:00:00
abstract::For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835861f6
更新日期:2012-10-01 00:00:00
abstract::Prognostic blood biomarkers for patients with uveal melanoma have not been identified. Tumor monosomy-3 is strongly associated with the development of metastatic disease. Tumor expression of human leukocyte antigen class I molecules and insulin-like growth factor (IGF)-1 receptor has also been associated with the deve...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835b7154
更新日期:2013-02-01 00:00:00
abstract::In metastatic melanoma (MM) immunomodulating agents, such as interleukin-2 (IL-2) and interferon-α (IFN-α), have shown therapeutic benefit as they enhance antitumor immune response. Considering tumor-induced suppression of natural killer (NK) cell activity, it is of interest to study the affect of these cytokines on t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32833e3286
更新日期:2010-12-01 00:00:00
abstract::Protein tyrosyl phosphorylation is an essential component in intracellular signalling, with diverse and crucial functions including mediation of cell proliferation, survival, death, differentiation, migration and attachment. It is regulated by the balance between the activities of protein tyrosine kinases (PTKs) and p...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/00008390-200010000-00001
更新日期:2000-10-01 00:00:00
abstract::Concurrent BRAF-MEK inhibition improves clinical outcomes in patients with advanced BRAF V600E/K-mutant melanoma. There is currently less evidence for the efficacy of this treatment in patients with rare BRAF non-V600E/K genotypes. We report on two patients with rare BRAF exon 15 mutations - BRAF A598_T599insV and V60...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000376
更新日期:2017-10-01 00:00:00
abstract::Loss of expression of E-cadherin, the major cell-cell adhesion receptor on keratinocytes, has been linked to tumour progression in various carcinomas. As E-cadherin has been reported to be expressed in cultured human melanocytes, we questioned whether loss of E-cadherin expression may also be related to melanocytic tu...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199604000-00007
更新日期:1996-04-01 00:00:00
abstract::Results obtained using a computerized image analysis system as an aid to clinical diagnosis of melanoma are reported. The system comprises a colour television camera connected through a digitizing board to a 386 personal computer. By means of original algorithms able to measure the shape, the colours and texture of a ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199209000-00004
更新日期:1992-09-01 00:00:00
abstract::Ipilimumab (anti-CTLA-4 antibody) is a new tool for the treatment of metastatic melanoma patients that has led to an improvement in survival rates worldwide. New types of toxicities have been described with ipilimumab called 'immune-related adverse events' or irAEs. Here, we report an acute and steroid resistant case ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835fb524
更新日期:2013-06-01 00:00:00
abstract::Familial atypical multiple mole-melanoma (FAMMM) syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combination with multiple atypical precursor naevi. In the present study we performed linkage analysis in seven Dutch FAMMM families to define the relationship between the ultimate...
journal_title:Melanoma research
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Cutaneous melanoma is one of the most lethal cancers because of its increased rate of metastasis and resistance to available therapeutic options. Early studies indicate that metformin has beneficial effects on some types of cancer, including melanoma. To clarify knowledge of the mechanism of action of metformin on thi...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000391
更新日期:2017-12-01 00:00:00
abstract::Dermatologic toxicity is a known reaction of ipilimumab and vemurafenib. Because of the lack of effective treatments and aggressive nature of melanoma, treatments are often discontinued and new treatments are initiated in rapid succession. We report what we believe to be the first case of cumulative dermatologic toxic...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000018
更新日期:2013-12-01 00:00:00