Alkylating benzamides with melanoma cytotoxicity.


: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.


Melanoma Res


Melanoma research


Wolf M,Bauder-Wüst U,Mohammed A,Schönsiegel F,Mier W,Haberkorn U,Eisenhut M




Has Abstract


2004-10-01 00:00:00














  • Malignant melanoma clinically mimicking pyogenic granuloma: comparison of clinical evaluation and histopathology.

    abstract::Amelanotic melanomas (AMMs) account for a small proportion of all melanomas. They pose a risk of delayed diagnosis and, consequently, poor prognosis. AMMs may atypically present as a pyogenic granuloma-like lesion. This study sought to investigate the prevalence and clinical and histological features of AMM masqueradi...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Moshe M,Levi A,Ad-El D,Ben-Amitai D,Mimouni D,Didkovsky E,Feinmesser M,Lapidoth M

    更新日期:2018-08-01 00:00:00

  • The prognostic role of CD4+ and CD8+ lymphocytes during chemoimmunotherapy in metastatic melanoma.

    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


    authors: Hernberg MM,Hahka-Kemppinen MH,Pyrhönen SO

    更新日期:2004-12-01 00:00:00

  • Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients.

    abstract::Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a pre...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Ahmad SS,Qian W,Ellis S,Mason E,Khattak MA,Gupta A,Shaw H,Quinton A,Kovarikova J,Thillai K,Rao A,Board R,Nobes J,Dalgleish A,Grumett S,Maraveyas A,Danson S,Talbot T,Harries M,Marples M,Plummer R,Kumar S,Nathan

    更新日期:2015-10-01 00:00:00

  • Inositol hexaphosphate plus inositol induced complete remission in stage IV melanoma: a case report.

    abstract::Inositol hexaphosphate (IP6) also called phytic acid is a polyphosphorylated carbohydrate naturally found in cereals, nuts, grains, and high-fiber-containing foods. It has been shown to inhibit the growth of many different tumor cell lines both in vitro and in vivo like colon, pancreas, liver, prostate, and even melan...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Khurana S,Baldeo C,Joseph RW

    更新日期:2019-06-01 00:00:00

  • Adjuvant external beam radiotherapy after therapeutic groin lymphadenectomy for patients with melanoma: a dosimetric comparison of three-dimensional conformal and intensity-modulated radiotherapy techniques.

    abstract::Radiotherapy after lymph node dissection is recommended in high-risk melanoma cases. The aim of this study is to assess whether intensity-modulated radiotherapy (IMRT) offers advantages over three-dimensional conformal radiotherapy (3DCRT) in the groin nodal basin. Fifteen consecutively treated patients (5 3DCRT and 1...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Adams G,Foote M,Brown S,Burmeister B

    更新日期:2017-02-01 00:00:00

  • Fatty acid receptor GPR120: a novel marker for human melanoma.

    abstract::The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of ...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Kleemann J,Hrgovic I,Ter-Nedden J,Kleimann P,Steinhorst K,Härle K,Müller J,Kaufmann R,Meissner M,Kippenberger S

    更新日期:2018-08-01 00:00:00

  • Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours.

    abstract::Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, ...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Sviatoha V,Tani E,Kleina R,Sperga M,Skoog L

    更新日期:2010-04-01 00:00:00

  • Statistical evaluation of epiluminescence microscopy criteria in the differential diagnosis of malignant melanoma and pigmented basal cell carcinoma.

    abstract::Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the ...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Püspök-Schwarz M,Steiner A,Binder M,Partsch B,Wolff K,Pehamberger H

    更新日期:1997-08-01 00:00:00

  • Modification of invasion and differentiation in human melanoma cell clones.

    abstract::In an attempt to define the role of plasminogen activator in invasiveness and differentiation of human melanoma cells, the modulation of these parameters was studied in two melanoma clones characterized by marked differences in their basal features, using 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and retinoic acid, ...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Supino R,Cecchi C,Mapelli E,Sanfilippo O

    更新日期:1994-08-01 00:00:00

  • TAP prefers to transport melanoma antigenic peptides which are longer than the optimal T-cell epitope: evidence for further processing in the endoplasmic reticulum.

    abstract::Many melanoma epitopes are presented to cytotoxic T-lymphocytes (CTLs) by major histocompatibility complex (MHC) class I molecules, and it is reasonable to expect that the epitopes would be good substrates for the transporter associated with antigen processing (TAP), as TAP plays a major role in the transport of pepti...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Wang Y,Guttoh DS,Androlewicz MJ

    更新日期:1998-08-01 00:00:00

  • Differential expression of the CD10 antigen (neutral endopeptidase) in primary versus metastatic malignant melanomas of the skin.

    abstract::The CD10 antigen is a neutral endopeptidase expressed by a variety of mesenchymal tumours (haemopoietic or not), including a subset of malignant melanomas. We investigated the expression of CD10 in formalin-fixed, paraffin-embedded tissue specimens of 72 cutaneous melanomas (28 primary, 26 metastatic to the skin and 1...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Kanitakis J,Narvaez D,Claudy A

    更新日期:2002-06-01 00:00:00

  • The effect of delay time between primary melanoma biopsy and sentinel lymph node dissection on sentinel node status, recurrence, and survival.

    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


    authors: Parrett BM,Accortt NA,Li R,Dosanjh AS,Thummala S,Kullar R,Cleaver JE,Kashani-Sabet M,Leong SP

    更新日期:2012-10-01 00:00:00

  • Microphthalmia transcription factor in malignant melanoma predicts occult sentinel lymph node metastases and survival.

    abstract::Microphthalmia transcription factor (Mitf) is involved in melanocyte development and differentiation. We previously reported that Mitf expression, as detected by immunohistochemical analysis, is an independent prognostic marker in patients with intermediate-thickness melanoma. However, the clinical significance of Mit...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Naffouje S,Naffouje R,Bhagwandin S,Salti GI

    更新日期:2015-12-01 00:00:00

  • Effect of Sideritis leptoclada against HT-144 human malignant melanoma.

    abstract::Sideritis leptoclada O. Schwarz et P.H. Davis extracts were evaluated for its singlet oxygen production capacity using spectrophotometric method. The extracts producing singlet oxygen were then evaluated for cytotoxicity against malignant melanoma cancer (HT-144) and fibroblast (3T3) cell lines using the 3-[4,5-dimeth...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Aydoğmuş-Öztürk F,Günaydin K,Öztürk M,Jahan H,Duru ME,Choudhary MI

    更新日期:2018-12-01 00:00:00

  • Lovastatin-induced apoptosis in human melanoma cell lines.

    abstract::The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell T...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Shellman YG,Ribble D,Miller L,Gendall J,Vanbuskirk K,Kelly D,Norris DA,Dellavalle RP

    更新日期:2005-04-01 00:00:00

  • Protein tyrosine kinases in malignant melanoma.

    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


    authors: Easty DJ,Bennett DC

    更新日期:2000-10-01 00:00:00

  • Defect of insulin receptor in insulin-resistant variants of Cloudman S91 mouse melanoma cells.

    abstract::To study the mechanisms by which insulin regulates proliferation, we have compared wild-type Cloudman melanoma cells, whose growth in inhibited by insulin (insinh) to variant lines that were genetically selected for resistance to insulin (insres). Scatchard analysis of insulin binding to five insres) lines and six ins...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Slominski A,McNeely T,Pawelek J

    更新日期:1992-07-01 00:00:00

  • Ribonucleotide diphosphate reductase from human metastatic melanoma.

    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


    authors: Schallreuter KU,Elgren TE,Nelson LS Jr,MacFarlan S,Yan-Sze I,Hogenkamp HP

    更新日期:1992-12-01 00:00:00

  • Skin cancer in children and young adults: 28 years' experience from the Northern Region Young Person's Malignant Disease Registry, UK.

    abstract::Little population-based data has been published about skin cancers in children and young adults. In this study, 200 cases of melanoma and non-melanoma skin cancers diagnosed under 25 years of age in the North of England from 1968-1995 were obtained from the Northern Region Young Persons' Malignant Disease Registry. Th...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Pearce MS,Parker L,Cotterill SJ,Gordon PM,Craft AW

    更新日期:2003-08-01 00:00:00

  • Spontaneous regression of transplacental metastases from maternal melanoma in a newborn: case report and review of the literature.

    abstract::We describe a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the second pregnancy of a 28-year-old woman. She was aware of a greyish-brown nodular lesion on the right gluteus during her first pregnancy. On histological examination, this lesion resulted to be an amelanocitic...

    journal_title:Melanoma research

    pub_type: 杂志文章,评审


    authors: Valenzano Menada M,Moioli M,Garaventa A,Nozza P,Foppiano M,Trimarchi N,Fulcheri E

    更新日期:2010-12-01 00:00:00

  • Production of superoxide by human malignant melanoma cells.

    abstract::Metastasis is a complicated multi-step process involving interactions between tumour cells, the extracellular matrix and the vessel walls. Experimental observations suggest that leucocyte migration and function could be a suitable model in order to understand tumour cell dissemination. In the present report we show an...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Bittinger F,González-García JL,Klein CL,Brochhausen C,Offner F,Kirkpatrick CJ

    更新日期:1998-10-01 00:00:00

  • Effects of interferon-alpha, verapamil and dacarbazine in the treatment of advanced malignant melanoma.

    abstract::Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-alpha (IFNalpha) as single drugs, or in combination, results in a response rate of approximately 15-20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFNalpha2b and verapamil (V...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Andersson R,Ake Hofer P,Riklund-Ahlström K,Henriksson R

    更新日期:2003-02-01 00:00:00

  • Intracellular signaling modules linking DNA damage to secretome changes in senescent melanoma cells.

    abstract::Cellular senescence is a major barricade on the path of cancer development, yet proteins secreted from senescent cells exert complex and often discordant effects on subsequent cancer evolution. Somatic genome alternations driving the formation of nevi and melanoma are efficient inducers of cellular senescence. Melanoc...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Chavanet A,Hill KR,Jiménez-Andrade Y,Choo MK,White K,Park JM

    更新日期:2020-08-01 00:00:00

  • Growth inhibition of subcutaneous mouse melanoma and induction of natural killer cells by liposome-mediated interferon-beta gene therapy.

    abstract::In this study we investigated the antitumour effect and mechanism of action of cationic liposome-mediated murine interferon-beta (IFNbeta) gene therapy in mouse B16F1 melanoma cells in vitro and in vivo. Murine IFNbeta gene transfer by cationic liposome resulted in substantial growth inhibition of B16F1 melanoma cells...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Ryuke Y,Mizuno M,Natsume A,Suzuki O,Nobayashi M,Kageshita T,Matsumoto K,Saida T,Yoshida J

    更新日期:2003-08-01 00:00:00

  • MicroRNA miR-125b induces senescence in human melanoma cells.

    abstract::MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melano...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Glud M,Manfé V,Biskup E,Holst L,Dirksen AM,Hastrup N,Nielsen FC,Drzewiecki KT,Gniadecki R

    更新日期:2011-06-01 00:00:00

  • Utility of 3-year torso computed tomography and head imaging in asymptomatic patients with high-risk melanoma.

    abstract::There is no general consensus regarding the optimal follow-up strategy for patients with melanoma. We sought to determine the utility and cost effectiveness of radiological restaging of patients with stage IIB-IIIC melanoma at the 3-year follow-up time point. A retrospective review of 210 patients diagnosed with stage...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: DeRose ER,Pleet A,Wang W,Seery VJ,Lee MY,Renzi S,Sullivan RJ,Atkins MB

    更新日期:2011-08-01 00:00:00

  • Anti-programmed cell death-1 therapy in octogenarian and nonagenarian advanced/metastatic melanoma patients.

    abstract::Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three pati...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Cybulska-Stopa B,Ziętek M,Kamińska-Winciorek G,Czarnecka AM,Piejko K,Galus Ł,Ziółkowska B,Kieszko S,Kempa-Kamińska N,Calik J,Zemełka T,Kubiatowski T,Suwiński R,Mackiewicz J,Rutkowski P

    更新日期:2021-02-01 00:00:00

  • Limitations of high frequency ultrasound in determining the invasiveness of cutaneous malignant melanoma.

    abstract::Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical ap...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Partsch B,Binder M,Püspök-Schwarz M,Wolff K,Pehamberger H

    更新日期:1996-10-01 00:00:00

  • Transarterial chemoembolization of liver metastases from uveal melanoma after failure of systemic therapy: toxicity and outcome.

    abstract::The liver is the predominant site of metastases in the majority of patients with uveal melanoma, suggesting the evaluation of regional treatment approaches. Here we report our experience with transarterial chemoembolization (TACE) in uveal melanoma patients with pretreated liver metastases. Twenty-five patients were t...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Schuster R,Lindner M,Wacker F,Krössin M,Bechrakis N,Foerster MH,Thiel E,Keilholz U,Schmittel A

    更新日期:2010-06-01 00:00:00

  • Biological and enzymatic features of human melanoma clones with different invasive potential.

    abstract::Cell clones derived from a human melanoma metastasis selected for different integrin profiles were examined in vitro for invasive potential and biological and biochemical features potentially related to this process. Clones which expressed high levels of integrins showed high invasive potential, extracellular matrix d...

    journal_title:Melanoma research

    pub_type: 杂志文章


    authors: Supino R,Mapelli E,Sanfilippo O,Silvestro L

    更新日期:1992-12-01 00:00:00