Sulphur mustard (SM) is an alkylating chemical warfare agent that was widely used during the World War I and in the Iran-Iraq conflict. Delayed complications of SM in different organs and their severity correlations have not previously been reported. Dermatological, ophthalmological, neurological and respiratory examinations, as well as spirometry, gasometry, high resolution computed tomography scanning of the chest, electromyography, nerve conduction velocity, cell blood counts, flow-cytometric analyses, and measurement of serum immunoglobulins and complement factors were performed on all severely SM poisoned veterans in the province of Khorasan, Iran. Haematological and immunological studies were also performed on a control group consisting of 35 healthy male subjects. The severity of dermal, ocular and respiratory complications were classified into four grades and their correlations with each other as well as with the haematological and immunological parameters were determined, using Spearman's rank correlation test. Forty male patients (aged 43.8 +/- 9.8 years) with confirmed SM poisoning 16-20 years after the exposure were studied. The most common complications were found in the lungs (95%), peripheral nerves (77.5%), skin (75%), and eyes (65%). WBC, RBC, haematocrit (HCT), IgM, C3, and the percentages of monocytes and CD3+ lymphocytes were significantly (P < 0.042) higher and the percentage of CD16 + 56 positive cells was significantly (P = 0.006) lower in the patients than in the control group. The severity of respiratory complications revealed a significant correlation with the severity of ocular complications (r = 0.322, P = 0.043), as well as with the haemoglobin (r = 0.369, P = 0.024) and HCT (r = 0.470, P =0.003). Although late complications of SM poisoning in the skin, eyes, and respiratory system are mainly due to its direct toxic effects, the neuromuscular, haematological and immunological complications are probably the result of systemic toxicity.

Background Studies have recently revealed that almost every type of cells including tumor cells abundantly release small vesicles known as extracellular vesicles (EVs) into the extracellular milieu. EVs carry a repertoire of biological molecules including nucleic acids, proteins, lipids, and carbohydrates and transport their cargo between cells in the vicinity as well as distantly located cells and hence act as messengers of intercellular communication. In this review, we aimed to discuss the tumor-derived exosome biology and the pivotal roles of exosomes in cancer diagnosis and treatment. Methods In the present review study, the authors studied several articles over the past two decades published on the kinetics of EVs in tumor environment as well as on the application of these vesicles in cancer diagnosis and therapy. Results A growing body of evidence indicates that nucleic acids such as microRNAs (miRNAs) transferring by EVs participate to create a conducive tumor environment. As EV-associated miRNAs are tissue-specific and present in most biological fluids, they hold great potential for clinical application in cancer early diagnosis, prognosis, and treatment response. Furthermore, exosomes can serve as drug delivery vehicles transferring miRNAs as well as therapeutic agents to target cells. These nano-vesicles exhibit ideal properties in comparison with the synthetic carriers that attracted scientist’s attention in the field of nanotechnology medicine. Scientists have employed different strategies to build exosomes-based drug delivery system. In general, two methods (direct engineering and indirect engineering) are being utilized to produce artificial exosomes. Para-clinical data have confirmed the beneficial effects of engineering exosomes in cancer therapy. Conclusion Exosomal miRNAs hold great promise for clinical application in early diagnosis and treatment of cancers. In addition, in spite of enthusiastic results obtained by engineered exosomes, however, there is an increasing concern over the use of optimal methods for engineering exosomes and the safety of engineered exosomes in clinical trials is still unclear.

Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-B activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferonalpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogenetargeted cancer therapy. (Blood. 2009; 113:6528-6532)

No abstract

No abstract