No abstract

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPR-Cas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a ‘molecular switch’ between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53-mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.

Extravasation of vesicant antineoplastic agents such as doxorubicin into the skin or subcutaneous tissues may result in loss of the full thickness of the skin or underlying structures. Several treatment methods have been advocated but none has demonstrated any superiority to the others. The authors designed a controlled animal study in 88 rats to test three methods of early treatment of extravasation of the vesicant antineoplastic agent doxorubicin. The first step of the study included 48 Sprague-Dawley rats. All animals received intradermal injections of 1 mg doxorubicin superficially to the panniculus carnosus in the dorsum. The rats were then divided into four groups of 12 rats each, as follows: group 1, no treatment; group 2, immediate intradermal injection of 0.1 ml saline to the same site; group 3, immediate intradermal injection of 10 microg granulocyte macrophage-colony stimulating factor (GM-CSF) in 0.1 ml saline to the same site; group 4, immediate intradermal injection of 10 microg granulocyte-colony stimulating factor (G-CSF) in 0.1 ml saline to the same site. During the next 6 weeks the rats were observed for the development of necrosis. Ulcers developed and reached maximum size two weeks after the injections. The largest ulcers according to area were observed in group 1 and the mean value was 21.25 mm (p < 0.05). Although wound areas were significantly smaller in the saline group than in the control group and the mean value was 7.58 mm (p < 0.05), the smallest lesions were observed in groups 3 and 4, and the mean values were 1.08 mm and 0.83 mm respectively (p < 0.05). There was statistically no difference with regard to mean ulcer area between groups 3 and 4. During the second step of the experiment, the remaining 40 Sprague-Dawley rats were used. Groups containing 10 rats each were designed similarly after all animals received intradermal injections of 1 mg doxorubicin into the back. On the 10th day after the injection, the entire area of the ulcer together with the underlying panniculus carnosus was excised for pathological examination and for determination of glucose 6-phosphate dehydrogenase (G6PD) activity. On microscopic examination, the extravasated ulcer consisted of a large area of ischemic necrosis. There was marked damage to small blood vessels in the form of fibrinoid necrosis and vasculitis. Injured vessel counts were higher in the control group (group 1; p < 0.05). No difference was observed in G6PD activity between the groups. The authors conclude that both saline and tissue growth factors (GM-CSF and G-CSF) are useful for the early treatment of doxorubicin extravasation; however, GM-CSF and G-CSF are more beneficial.

Zoledronic acid may be associated with inflammatory eye diseases and result in serious ocular damage.