Thalidomide: A review of approved and investigational uses

Matthews, S. James; McCoy, Christopher

doi:10.1016/s0149-2918(03)80085-1

Cited by 193 publications

(129 citation statements)

References 156 publications

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“…Here we show conclusively that loss of newly formed blood vessels is the primary cause of thalidomide teratogenesis, and developing limbs are particularly susceptible because of their relatively immature, highly angiogenic vessel network. We also demonstrate that these effects correlate to the increased fetal loss and developmental-time-sensitive action of thalidomide (2,3,(6)(7)(8).…”

mentioning

confidence: 53%

“…It caused an increase in miscarriage and still birth rates and a 40% increase in infant mortality, and up to 10,000 children around the world were born with severe limb malformations, as well as other much less common congenital defects (1)(2)(3)(4)(5)(6)(7). Children with such defects are still being born today, particularly in Africa and South America, where thalidomide is now increasingly used in treating leprosy (8,9).…”

mentioning

confidence: 99%

“…Over 80% of children born to mothers who took thalidomide had limb defects (2,3,5,6). These defects ranged from absence of the limb (amelia) or proximal limb elements (phocomelia) to loss of the thumb or digit tip and are induced in a small time-sensitive developmental window (2,3,(6)(7)(8). The precise mechanism underlying thalidomide's teratogenic effects, its relative limb specificity, and the range of induced defects have not been established.…”

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confidence: 99%

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Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

Therapontos

Erskine

Gardner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

226

319

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Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level. Antiangiogenic but not antiinflammatory metabolites/analogues of thalidomide induce chick limb defects. Both in vitro and in vivo, outgrowth and remodeling of more mature blood vessels is blocked temporarily, whereas newly formed, rapidly developing, angiogenic vessels are lost. Such vessel loss occurs upstream of changes in limb morphogenesis and gene expression and, depending on the timing of drug application, results in either embryonic death or developmental defects. These results explain both the timing and relative tissue specificity of thalidomide embryopathy and have significant implications for its use as a therapeutic agent.blood vessels ͉ chick limb development ͉ thalidomide analog ͉ angiogensis ͉ zebrafish

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mentioning

confidence: 53%

mentioning

confidence: 99%

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confidence: 99%

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Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

Therapontos

Erskine

Gardner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

226

319

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“…51,52 Patient 3 at various times was taking thalidomide and interferon alpha in addition to CLT. Thalidomide is an antiangiogenic agent with known anticancer potency 53 while interferon alpha is an immunomodulatory agent frequently used as an adjuvant cancer treatment. 54 The subjective improvement initially experienced by a few other patients was either not confirmed by objective tests or may have been due to chemotherapy or radiation taken immediately before CLT.…”

Section: Discussionmentioning

confidence: 99%

Patient Responses to Cytoluminescent Therapy ® for Cancer: An Investigative Report of Early Experiences and Adverse Effects of an Unconventional Form of Photodynamic Therapy

Moss

2003

Integr Cancer Ther

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Therapy ® (CLT) is an unconventional form of photodynamic therapy (PDT), utilizing a secondgeneration chlorophyll-derived photosensitizing agent and whole-body illumination. Starting in late 2002, CLT was administered in Ireland to 48 patients. Illumination with lasers and light-emitting diodes followed the administration of an initial bolus IV. After returning home, patients continued self-administered treatment using oral agent activated by infrared lamps. CLT proponents claimed that these procedures were beneficial to patients with advanced cancer. An organization devoted to making information on alternative therapies available to the public was engaged to contact these CLT patients and assess the outcome. In informal contacts, patients reported that initial side effects were generally mild and transient. However, especially after commencing self-treatment, many reported unanticipated effects, including fatigue and general weakness, increased pain, cough, dyspnea, diminished appetite and weight loss, tissue necrosis, and other major symptoms. At a minimum of 6 months after initial CLT, no patient has reported an objective response, and some have complained of deterioration on the home treatment. There have been 17 deaths among the 48, with a mean survival after initial treatment among decedents of 4.2 months. CLT, in this group, was a qualified failure, with a high incidence of aftereffects. The mode of action of these aftereffects has yet to be explored. In the future, CLT should be administered to patients only in carefully managed medical facilities, by fully trained and licensed professionals, under the supervision of relevant regulatory agencies, and with meticulous follow-up care.

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“…许多药物的两个对映异构体在体内的药理活性、代谢过程、速率及毒性等差异显著, 单一构象手性药物的需求及对药物药理和毒理的关注与日剧增 [3,4] . 因此, 手性分离成为当前研究的热点和难点 [5] .…”

Section: 引言unclassified

Construction and Chromatographic Performance of a Novel Triazole Bridged Hybrid Bilayer Cyclodextrin Chiral Stationary Phase

Zhang¹,

Jie²,

Wang³

2015

Acta Chim. Sinica

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Thalidomide: A review of approved and investigational uses

Cited by 193 publications

References 156 publications

Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

Patient Responses to Cytoluminescent Therapy ® for Cancer: An Investigative Report of Early Experiences and Adverse Effects of an Unconventional Form of Photodynamic Therapy

Construction and Chromatographic Performance of a Novel Triazole Bridged Hybrid Bilayer Cyclodextrin Chiral Stationary Phase

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