Bexarotene – an alternative therapy for progressive cutaneous T‐cell lymphoma? First experiences

Bohmeyer, J.; Stadler, Rudolf; Kremer, Almut; Nashan, Dorothée; Muche, Marion; Gellrich, Sylke; Luger, T.A.; Sterry, Wolfram

doi:10.1046/j.1439-0353.2003.03711.x

Cited by 6 publications

(3 citation statements)

References 25 publications

(23 reference statements)

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“…These treatments leave many side effects on patients. Therefore, alternative therapy gradually become popular amongst those affected, where are vomiting, hair loss, diarrhea, and other side effects are not a part of the treatment . In addition, there were some references which is inducing human liver, gastric, lung, cervical cancer cell lines, and so on.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, alternative therapy gradually become popular amongst those affected, where are vomiting, hair loss, diarrhea, and other side effects are not a part of the treatment. 20 In addition, there were some references which is inducing human liver, gastric, lung, cervical cancer cell lines, and so on. However, our study is the first manuscript to demonstrate that MHA, acetone extraction of Clinacanthus nutans have better anti-cancer cells proliferation than hexane, ethanol even water extracts.…”

Section: Resultsmentioning

confidence: 99%

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Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP‐T1 cells

Hsieh

et al. 2018

Environmental Toxicology

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Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia. The in vitro cellular study showed the chloroform extract possessed significant cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study reported that administration of plant could treat or prevent relapse in 12 cancer patients. However, detailed mechanism of the anticancer effects and chemical profiles are not thoroughly studied. The chemical study did show that the acetone extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT-4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as demonstrated by annexin-V/PI, JC-1, H DCFDA, and Flou-3 staining assays, respectively. MHA-induced ER stress was confirmed by increase expression of CHOP and IRE-1α with western blotting assay. In conclusion, we identified good bioactivity in Clinacanthus nutans and recognize its potential effect on cancer therapy, but further research is needed to determine the use of the plant.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP‐T1 cells

Hsieh

et al. 2018

Environmental Toxicology

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“…In two international multicentre phase II and III studies an overall response rate of 54% in early stage (IA–IIA) CTCL and of 45% in advanced stages (IIB–IVB) could be achieved 3,4 . In Europe, 10 patients in advanced stages of CTCL were treated in a pilot project, but the authors conclude that at present, bexarotene cannot be recommended as a standard therapy 5 . A larger multicentre study, organized by the Dermatological Cooperative Oncology Group (ADO) has just been initiated.…”

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confidence: 99%

Treatment of mycosis fungoides with bexarotene and psoralen plus ultraviolet A

Coors¹,

Driesch²

2005

Br J Dermatol

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Indeed, no correlation was observed between BM histology and outcome. Among the three patients with a second atypical BM, one died 1 year later due to septicaemia but without progression of his lymphoma, while the other two were still alive in partial remission after 48 and 72 months, respectively. On the other hand, five patients with progressive disease at the time of the second BM biopsy exhibited a normal BM histological pattern and three of them (patients 2, 11 and 12) died of lymphoma after 48, 2 and 6 months, respectively, with nodal (two cases) and meningeal (one case) involvement.No correlation was observed between histological pattern and molecular results in the second BM biopsy. The three patients with an atypical BM had either a polyclonal profile, an unrelated T-cell clone, or a medullary T-cell clone identical to skin and blood. Alternatively, a BM T-cell clone was found identical to skin and blood in four patients with normal BM histology. Interestingly, the molecular profiles of the first and second BM samples were identical in 10 of the 12 patients, including the five patients with an identical skin, blood and BM T-cell clone. Three of these five patients died of lymphoma and one had disease progression. As reported at diagnosis, 8 the monoclonal T-cell population detected in the second BM sample was already present in blood samples. The patients were already known to have progressive disease owing to clinical and biological status, except for one patient (patient 8) who is still in remission after 12 months. Such data would also suggest that monoclonal T-cells persist in consecutive blood and BM samples.Although the small number of patients with a second BM biopsy does not allow statistical conclusions to be drawn, the comparative analysis of a second BM specimen reinforces the conclusions of our first study. First, BM histological involvement is very rare in patients with epidermotropic lymphoma both at diagnosis and during follow-up. Second, BM histological and molecular staging does not provide any further information useful for patient management. Finally, we suggest that BM biopsy is of little value, not only at diagnosis but also during follow-up, unless specific haematological symptoms are present.

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Retinoids

Dawson¹

2010

Burger's Medicinal Chemistry and Drug Discovery

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Retinoid drugs find major applications in the topical treatment of cutaneous proliferative disorders such as acne, psoriasis, and photoaging and cutaneous cancers such as cutaneous T‐cell lymphoma (CTCL) and Kaposi's sarcoma. Oral retinoids are successfully used to treat nodular/cystic acne, systemic CTCL, and acute promyelocytic leukemia. This overview of available retinoid drugs and those in the preclinical or clinical pipeline covers their development, indications, clinical trial results, adverse effects, and pharmacology/metabolism. Retinoids have been described historically and functionally in the context of interaction with their nuclear receptors—retinoic acid receptors (RARs) and retinoid X receptors (RXRs)—in inducing gene transcription. RAR‐selective retinoids or their prodrugs include first‐generation all‐ trans ‐retinoic acid (tretinoin) and its 13‐ cis isomer (isotretinoin), and second‐generation acitretin and its ethyl ester (etretinate), both having an aromatic 2,3,6‐trimethyl‐4‐methoxyphenyl terminus. Third‐generation more aromatic analogs include ethyl ester tazarotene (Tazorac®) and adapalene (Differin®), both selective for RAR subtypes β and γ, and RARα‐selective pipeline candidates Am80 and NRX 195183, which are in clinical trials. RAR and RXR transcriptional panagonist 9‐ cis ‐retinoic acid is next and is followed by RXR‐selective bexarotene (Targretin™) and two RXR‐selective clinical trial candidates, 9cUAB and NRX 194204. The fourth generation includes three compounds that may have applications in the treatment or prevention of cancer. While originally considered as retinoids, such as N ‐(4‐hydroxyphenyl) retinamide, or as retinoid‐related or derived, such as ST1926 (AHPC) and SHetA2, they subsequently were found to function independently of the RARs and RXRs in inhibiting cancer cell proliferation and inducing apoptosis.

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Bexarotene – an alternative therapy for progressive cutaneous T‐cell lymphoma? First experiences

Abstract: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Cited by 6 publications

References 25 publications

Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP‐T1 cells

Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP‐T1 cells

Treatment of mycosis fungoides with bexarotene and psoralen plus ultraviolet A

Retinoids

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