The risk of angiosarcoma following primary breast cancer

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart–Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266 444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9–152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3–26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1–1.7). © 1999 Cancer Research Campaig

Resolving the diagnostic dilemma of T-cell clonal expansion after hematopoietic stem cell transplantation in T-cell lymphoma patients by TCR-gamma next generation sequencing

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Is there a future for mGlu5-positive allosteric modulators in absence epilepsy? A comparison with ethosuximide

Contains fulltext : 175798.pdf (Publisher’s version ) (Open Access)Ethosuximide is the drug of choice in the treatment of various types of absence seizures. However, there is plenty of room for other anti-absence drugs, considering that not all subjects (57-74%) become seizure-free and about 47% of ethosuximide therapy fails. New anti-absence drugs may target or modulate glutamatergic and or GABAergic neurotransmission, the key players in the circuitry involved in the cortico-thalamo-cortical oscillations responsible for the highly stereotyped spike-wave discharges (SWDs). Cortical highly excitable cells in the focal region form the trigger for the occurrence of SWDs. In contrast, enhanced tonic inhibition is dominant in the thalamus. Biochemical studies have shown that symptomatic WAG/Rij rats differ from age-matched controls in metabotropic glutamate (mGlu) receptor expression and function: mGlu5 receptor expression and function are increased in the somatosensory cortex, and mGlu1 receptor expression is decreased in the thalamus. The two group I mGlu receptor-positive allosteric modulators (PAMs) VU0360172 and RO0711401 have an interesting profile in acute and (sub)chronic pharmacological studies and produce a dose-dependent decrease of SWDs. Moreover, both compounds are effective in reducing SWDs in the cortex and thalamus. Interestingly, the GABA reuptake blocker tiagabine reduces SWDs in the cortex and not in the thalamus, while the efficacy of ethosuximide is higher in the cortex than in the thalamus. It is thought that VU0360172 stimulates cortex GABA interneurons, which inhibit highly excitable cortical neurons in the focal area. In the thalamus, VU0360172 most likely reduces tonic inhibition. Thus, group I mGlu receptor PAMs might be further developed as anti-absence drugs, with putative disease-modifying effects on epileptogenesis. The preclinical profile of group I mGlu receptor PAMS deserves to be further explored in models of generalized epilepsy and focal types of epilepsy