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PubMed2006

Primary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with multiple myeloma.

Fifty patients with multiple myeloma >or=75 years of age received primary treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20. This regimen was repeated every 5 weeks for three courses. Patients without evidence of disease progression received nine additional courses of MDT, but without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a partial response and 10% a complete response. The median time to response was 2 months. The median time to progression for all patients was 21.2 months. Deep venous thrombosis and peripheral neuropathy each occurred in 9% of patients.

Aged↗
PubMed2006

[Refractory anaemia successfully treated with thalidomide].

A 63-year-old male was admitted to our department in 2001 because of autoimmune haemolytic anaemia and splenomegaly. Bone marrow examination revealed an erythroid hyperplasia and a normal chromosome analysis. Splenectomy was performed in 2002, resulting in severe transfusion-dependent anaemia with a need for two blood transfusions each week. Treatment with prednisolone, erythropoietin and danocrine was without effect. A new bone marrow examination then showed myelodysplastic syndrome. Treatment with thalidomide, 50-150 mg/d, and prednisolone, 25 mg/d, resulted in an increase in haemoglobin to 8.9 mmol/l during the following months. The use of immunomodulatory and anti-angiogenetic agents in refractory anaemia needs more study.

Anemia, Refractory↗
PubMed2005

Extensive chronic graft-versus-host disease of skin successfully treated with thalidomide.

Thirty years female underwent allogenic peripheral blood stem cell transplantation for chronic myeloid leukaemia--chronic phase. She developed grade II acute skin graft-versus-host disease (GVHD) which was treated with cyclosporine and a short course of steroids. She developed extensive chronic GVHD of the skin and liver three hundred days post-transplant. She was managed with the standard immunosuppressants with partial response of liver dysfunction but no response of skin lesions. She showed a good response to therapy with resolution of skin lesions after treatment with thalidomide.

Adult↗
PubMed2006

Antiangiogenic agent, thalidomide increases the antitumor effect of single high dose irradiation (gamma knife radiosurgery) in the rat orthotopic glioma model.

Gliomas are primary brain tumors associated with a poor prognosis partly due to resistance to conventional therapies. To overcome this problem, we investigated the combined effects of gamma knife radiosurgery (GKS) and an antiangiogenic agent, thalidomide (THD), or a chemotherapeutic agent, temozolomide (TMZ), on a rat glioma model. GKS (20 Gy single dose) alone and/or drugs (for 3 days) were delivered 14 or 18 days after stereotactic implantation of C6/LacZ glioma cells into the brains of Sprague-Dawley rats. A group of animals treated with or without drugs for 3 days was irradiated on day 18 and sacrificed at 24 h after GKS to evaluate cell proliferation, apoptosis and microvessel density. The other group of animals was irradiated on day 14 and sacrificed at day 5 after GKS for the measurement of tumor volume. Apoptosis of endothelial cells in the tumor beds was only observed in the early period after GKS. Decreased cell proliferation and increased tumor cell apoptosis were observed in rat gliomas treated with GKS and THD or TMZ. The combination treatments with GKS and THD or GKS and TMZ also decreased microvessel density, i.e. angiogenesis, more effectively compared with GKS treatment alone. The combination of GKS and THD was the most effective regimen, resulting in a significant decrease of tumor volume. We suggest that the antitumor effect of GKS on glioma is enhanced by the addition of THD. Therefore, combined therapy with GKS and THD might be a favorable treatment for gliomas.

Angiogenesis Inhibitors↗
PubMed2006

[Experimental study of the anti-tumor effect of arsenic trioxide or thalidomide alone and combination of both for treatment of myelodysplastic syndrome model].

OBJECTIVE: To investigate the anti-tumor effect and the possible mechanism of arsenic trioxide (ATO) alone or in combination with thalidomide (THAL) for treatment of SCID mice model transplanted with human myelodysplastic syndrome (MDS) cell line MUTZ-1 cells. METHODS: (1) The animal model was established in SCID mice; 75 SCID mice and 10 BALB/CA-nude mice were studied in this experiment. MUTZ-1 cells were cultured in vitro and made for mono-cell suspension (with 1 x 10(8)/ml cell density and in exponential growth behavior) and were subcutaneously implanted into 4-6-week-old first-generation SCID mice and BALB/CA-nude mice. The biological characteristics of the subcutaneous tumor cells were evaluated by the methods of cell morphology, histopathology, immunology by flow cytometer, chromosome analysis and immunohistochemistry (IHC). Subsequently, the tumor cells from first-generation mice model were respectively subcutaneously implanted into 61 second-generation SCID mice and 8 BALB/CA-nude mice and the rate of the tumor formation and the latent period of the tumor formation were observed. (2) In vivo, 56 MDS-SCID mice were randomly grouped; 40 of them were used as ATO treated groups [5.0 microg or 7.5 microg/(g.d) intraperitoneal injection (i p) 5 d a week, x 3 weeks] alone or in combination with THAL 8 microg/(g.d), x 3 week or THAL alone and 16 mice as the control groups [with 0.9% NaCl 10 microl/(g.d) i p or untreated]. The mean tumor diameters (MTD) of subcutaneous tumors were measured with slide gauge and the therapeutic effects and the survival period and the rates of survival were evaluated by the methods of histopathology, IHC, microvessel density count (MVD), DNA ladder, TUNEL and PI with flow cytometry. RESULTS: (1) The rate of the subcutaneous tumor formation was higher (98.4%, 60/61) in SCID mice than in BALB/CA-nude mice (62.5%, 5/8) (P = 0.0027). The latent period of the tumor formation was significantly longer (23 - 28 d, median 26 d) in BALB/CA-nude mice than that in SCID mice (10 - 17 d, median 12 d) (Z = 4.605, P < 0.001). The biological characteristics of the tumor cells in the MDS-SCID mice model were evaluated and considered as of anthropo-source and were consistent with that of MUTZ-1 cells, which showed that the MDS-SCID mice model was successfully established. (2) In vivo, the marked inhibitory effect on the subcutaneous tumors growth (F = 146.94, P = 0.000) and the higher rates of cells apoptosis were seen in the groups treated with ATO 5.0 microg or 7.5 microg alone or in combination with THAL than in control groups (F = 30.10, P = 0.000). The longer-survival periods (F = 25.11, P < 0.01) with lower toxicity were only observed in lower-dose group of ATO 5.0 microg than in other treated groups and control groups. THAL alone group had a mild inhibitory effect on the tumors growth (> 2 weeks) with a longer-survival period and higher-rate of survival than controls, but had no events of cell apoptosis. The expression of vascular endothelial growth factor (VEGF) protein and CD34 protein and MVD were markedly down-regulated by THAL compared with control groups (P < 0.01), suggesting that the possible mechanisms of the inhibitory effect on tumor growth by THAL related to inhibition of vascular endothelial growth. The legs paralysis in 2 MDS-SCID mice was observed after treatment with THAL alone (11 d and 15 d, respectively), which were considered as the side-effect of THAL associated with deep venous thrombotic (DVT) events and the mechanism for these events is unclear. The therapeutic effects were unsatisfied in the group treated with ATO 7.5 microg in combination with THAL due to more intense toxicity and the shorter-survival periods than other treated groups (P < 0.001). CONCLUSIONS: (1) The Hum-MDS-SCID mice model was successfully established, which served as an animal model for studying pathogenesis of MDS and therapeutic agents selection. (2) ATO had marked inhibitory effect on the subcutaneous tumors growth in MDS-SCID mice model in vivo. The longer-survival periods and higher-rates of survival with lower toxicity were observed in lower-dose ATO (5.0 microg) alone than other groups. The mechanisms of the anti-tumor effect of ATO were considered to be related to inducing cells apoptosis, but in the case of THAL, related to inhibition of vascular endothelial growth. (3) The results do not support the preconceived hypothesis of a synergistic effect of ATO (7.5 microg) in combination with THAL for treatment of MDS mice model due to the more intense toxicity and the shorter-survival periods in the treated group. Whether or not this will translate into clinically relevant effect of the ATO or THAL in MDS patients deserves further investigation.

Animals↗
PubMedDate not supplied

Thalidomide radiosensitization of normal murine hematopoietic but not squamous cell carcinoma or multiple myeloma tumor cell lines.

BACKGROUND: Thalidomide (TL), due to its antiangiogenic effects, has been postulated to be a potential radiosensitizer of multiple myeloma and squamous tumors in vivo. MATERIALS AND METHODS: To determine whether TL was a radiosensitizer, 32D cl 3 cells (hematopoietic progenitor) as well as SCC-VII (squamous cell carcinoma), OPM1 or OPM2 (multiple myeloma) tumor cells were irradiated to doses ranging from 0 to 8 Gy and then plated in 0, 50 or 150 microM TL in each of three protocols: i) 1 hour before irradiation; ii) 1 hour before irradiation and also in medium following irradiation; or iii) placed in TL containing medium following irradiation. RESULTS: Using 150 microM TL (which did not stimulate cell growth) the 32D cl 3 cells had increased radiation sensitivity compared to the control irradiated cells. In contrast, the SCC-VII, OPMI or OPM2 cells showed no detectable radiosensitization when incubated in TL before, during or after irradiation compared to the control irradiated cells. CONCLUSION: These results demonstrated that TL may be a selective radiosensitizer.

Animals↗
PubMed2006

Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma.

We evaluated the combination of thalidomide, pulsed dexamethasone and weekly cyclophosphamide (CTD) for the treatment of patients with newly diagnosed, relapsed or VAD-refractory multiple myeloma. We found that this combination was highly effective in inducing responses in all treatment groups with an overall response rate of 83.8%. CTD was well tolerated and did not impair stem cell mobilization.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Thalidomide suppresses melanoma growth by activating natural killer cells in mice.

Although thalidomide (Thd) is being extensively investigated for its effects on cytokine production and T cell costimulation, it is poorly understood whether it is capable of modulating the activities of natural killer (NK) cells. In this study, Thd effects on NK cell activity were examined with a murine model of melanoma, which is mostly rejected by NK cell-dependent mechanism. Administration of Thd significantly (p<0.01 on Day 21) suppressed the growth of subcutaneous B16F1 melanoma. In Thd-treated mice, marked splenomegaly and augmented splenocyte count were observed. Additionally, the percentage of splenic NK1.1+ cells was elevated to approximately 2.5-fold within 10 days after Thd treatment. The expression of interferon inducible protein (IP)-10, interferon (IFN)-gamma, interleukin (IL)-12 and IL-18 was remarkably upregulated. Production of the cytotoxic molecule perforin was also augmented. These data suggest that Thd strongly activates NK cell activity in mice, possibly resulting in enhanced tumor surveillance defense.

Actins↗
PubMed1989

[Producing technical drawings using the feet--a special work site for a thalidomide-damaged technical draftswoman].

Persons with upper limb deficiency do not find it easy to lead a somewhat "normal" private, occupational and social life. True, society offers many kinds of assistance and support; it nevertheless is very much a matter of how the individual concerned reacts to the positive and negative influences and imponderabilities encountered. The present report sets out the efforts of a thalidomide-affected young woman who, in the face of numerous obstacles, left nothing untried to create a life basis of her own by obtaining a good vocational qualification as a technical draftswoman, regardless of her congenital upper limb amputation. Her success is proof enough that she chose the right course. This example, in more general terms, should perhaps be considered a prompting for society, on the one hand, to undertake the endeavour of providing quality assistance even in extreme situations and, on the other, to be prepared to have confidence even in those with very severe physical disablement to be able to accomplish goals which at the first glance may appear "nonsensical", such as a desire to be trained as a technical draftswoman even though one's hands are missing. The account not least shows the positive impact help and self-help may have in the rehabilitation of very severely disabled persons. The disabled person's reward primarily lies in the sense of independence achieved and in financial self-reliance, which in turn generate a sense of feeling free inwardly and outwardly.

Adult↗
PubMed1986

Immunological effects of thalidomide. Inactivity of the drug and several of its hydrolysis products in mononucleocyte proliferation tests.

In order to study the spontaneous degradation of thalidomide (N-phthalyl-glutamic acid imide), an HPLC method for the separation of the drug and its hydrolysis products was developed. The effect of these substances upon the proliferation of lectin- and allogeneically stimulated peripheral blood mononucleocytes was studied, using the incorporation of [3H]-thymidine as a marker. In contrast to optically evaluated experiments reported earlier, no inhibition of [3H] incorporation was found, regardless of the duration, mode, or timing of stimulation.

Cell Division↗
PubMed1985

[Neuropathies caused by thalidomide].

Symptoms and signs in four patients with thalidomide-induced neuropathy developing during treatment of discoid lupus were limited for long period to distal paresthesiae with altered sensory conduction velocities. Semi-thin biopsy specimens of the distal sural nerve showed depopulation of myelinized fibers, mainly affecting those of large caliber, and signs of axonal degeneration. Study of dissociated fibers showed a high proportion of E fibers. Morphometry confirmed the axonal lesion. Ultrastructural examination demonstrated anomalies of axons of amyelinic fibers (vacuoles, lamellar figures) and of Schwann cells (stacked cytoplasmic prolongations), together with numerous collagen pockets, all non-specific lesions. The disease course was slow, with disappearance of sensory symptoms in a few weeks in 3 of the 4 cases and normal clinical findings in one of the four patients one year after cessation of treatment. Definite correlations between the dose administered and the severity of the neuropathy could not be established. The still poorly understood mechanism of action is discussed.

Acute Disease↗
PubMed1979

[Motor-conduction velocity of cubital nerves in patients with leprosy reactions. Summary of a 13-year observation series during thalidomide therapy].

The motor conduction velocity of the ulnar nerves was examined repeatedly in 34 patients with lepromatous leprosy. In patients with active lesions the reduction in velocity paralleled clinical deterioration. In "burned-out" control patients, who had never suffered from leprosy reaction, the conduction velocity remained slow and unchanged over many years. Twenty-six of 34 patients suffering from leprosy reaction received Thalidomide treatment over a period of 6-13 years in order to suppress the reaction, with good effect. In none of these 26 patients neurotoxic disturbances were found.

Adult↗
PubMed1979

[The behavior of the facial nerve in vitamin A and thalidomide induced atresia auris congenita. A microsurgical and histological animal study (author's transl)].

Atresia auris congenita may include either a complete or incomplete paralysis of the facial nerve as well as a possible abnormal course of its tympanic segment. Pregnant Wistar rats were given high doses (50,000, 80,000 or 100,000 USP units) of vitamin A and (10,15 or 20 mg) Thalidomide on the 8th, 9th, 10th and 11th days of gestation. The animals were then sacrificed, and the temporal bones and the medulla oblongatas of the fetuses and the adult rats were examined microsurgically and histologically. In contrast to previous reports in the literature, no significantly abnormal courses of the nerve could be found. These findings corresponded to those of 62 endaurally operated human ear malformations. The paralysis of the facial nerve in these patients seems due to a reduced diameter of the nerve and not to a malformation of its nucleus.

Animals↗
PubMed1978

[Studies on possible interactions of thalidomide and genetic material from chicken embryos (author's transl)].

Tritium labelled thalidomide was applied to chicken embryos of various stages and the distribution of the readioactive label was investigated. No specific binding tendency to components of the cell could be found, especially no affinity to nucleic acids and to the chromosomal proteins (histones and non-histones) could be observed, which had been discussed hypothetically. An influence on DNA replication and transcription rate could also not be detected.

Animals↗
PubMed1966

Medical and psychosocial aspects of the habilitation of thalidomide children.

The habilitation of 34 thalidomide children, begun in 1963 at the Rehabilitation Institute of Montreal, involved the contribution of many medical and paramedical disciplines. These individual contributions are described.Habilitation of congenitally deformed children must be initiated at an early age. The early prescription of a prosthesis is desirable. Their care involves a broad range of services that must be continued over many years. Parents require support before they can accept the misfortune that has befallen them and their deformed child. Despite the necessity of frequent hospitalizations, children should be reared in a home setting. From their experience, the authors conclude that children born with malformations, and their parents, should be thoroughly evaluated and followed up for many years; and recommend that governments should finance programs for the complete habilitation of all children born with congenital malformations. National registries for the compulsory recording of birth deformities should also be established.

Abnormalities, Drug-Induced↗
PubMed1984

Thalidomide treatment of prurigo nodularis.

Four patients with classic recalcitrant prurigo nodularis had symptomatic and physical responses to thalidomide with remissions. Three of the four patients had increased IgE levels that decreased during therapy. In two patients, short-term treatment (2 to 3 months) was not sufficient to produce remission, but retreatment was effective. Two patients had long-term remission with more than 6 months of treatment. No significant side effects occurred.

B-Lymphocytes↗