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Epigenetic changes play a crucial role in leukemogenesis. HDACs are frequently recruited to target gene promoters by balanced translocation derived oncogenic fusion proteins. As important epigenetic effector mechanisms, histone deacetylases (HDAC) have emerged as potential therapeutic targets. However, the patterns of HDAC1 localization and the role of HDACs in leukemia pathogenesis remain to be elucidated. Using ChIP-Chip analyses we analyzed HDAC1 deposition patterns at more than 10,000 gene promoters in a large cohort of leukemia patients and CD34+ controls. HDAC1 binding was significantly increased in AML blasts compared to CD34+ progenitor cells at 130 gene promoters whereas decreased binding was observed at 66 gene promoters. Distinct HDAC1 binding patterns occurred in AML subtypes with balanced translocations t(15;17), t(8;21) and inv(16). In addition, a more generalized signature was established, that revealed an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered promoters regulate genes involved in hematopoiesis, transcriptional regulation and signal transduction. HDAC1 binding patterns were associated with patients' event free survival. This is the first study to determine HDAC1 modification patterns in a large number of AML and ALL specimens. Our findings suggest that dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1 modifications possess prognostic power for patient survival. Our findings suggest that altered HDAC1 localization is an explanation for the observed benefit of HDAC inhibitors in AML therapy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Cyanovirin-N (CV-N) is a prokaryotic protein under development as a topical anti-HIV microbicide, an urgent and necessary approach to prevent HIV transmission in at-risk populations worldwide. We have expressed recombinant CV-N as inclusion bodies in the cytoplasm of Escherichia coli. A purification scheme has been developed that exploits the physicochemical properties of this protein, in particular its stability in a harsh inclusion body purification scheme. Under the conditions developed, this system yields 140 mg of highly purified CV-N per liter of high-density cell culture, which represents a 14-fold increase over the best recombinant CV-N yield reported to date. This purification scheme results in monomeric CV-N as analyzed by SDS-PAGE, isoelectric focusing, and reverse phase- and size exclusion-HPLC. This recombinantly expressed and refolded CV-N binds to gp120 with nanomolar affinity and retains its potent anti-HIV activities in cell-based assays. The expression and purification system described herein provides a better means for the mass production of CV-N for further microbicide development.

The efficacy of an association of cyclophosphamide (CPM) and 5-fluorouracil was studied in 15 patients with prostate cancer not responding to oestrogen therapy, and more particularly its effect on pain due to bone metastases. No objective improvement was noted with this association, but there was a definitite reduction in bone metastases pain in 5 of the patients, with an average remission time of 4 months. Half of the patients had nausea and vomiting, but in spite of this digestive intolerance those patients who obtained pain relief for 4 months considered the treatment to be of positive value. This therapy is recommended only fater the failure of castration, anti-androgens, and oestrogens, together with nitrogen mustard (Estracyt) and corticotherapy.

Repeated dialysis in hospital or at home, and renal transplantation, carried out mainly with cadaver kidney, should permit in France, in the near future, treatment of all patients with chronic terminal renal failure. This report shows the results obtained between the 1st of November 1972 and the 1st of January 1975 in 136 patients treated without any selection at the Nephrology Department and Renal Transplantation Unit of the Pitié-Salpĕtrière Hospital in Paris, in connection with 20 public and private dialysis centers. 66 patients, i.e. 45% of all, were "high risk" patients, mainly because of their age or cardiovascular condition. The overall percentage of survival rate at 2 years in dialysed patients was 81%. It was 67% in the high risk group and 94% in the others. About half of the deaths occured because of cardiovascular reasons. 82 patients were considered for transplantation. Owing to the lack of donors, the number of transplanted patients was only 21. 19 transplantations were carried out with cadaver kidneys. On the 31st of December 1974, 15 patients, i.e. 71% lived with a functioning transplant. In the reported series, complete rehabilitation was obtained in 30% of cases. The results obtained justify, in our opinion, the policy of non-selection of patients.

Nine cases of malignant adrenal cortical tumour treated during the last decade are reported. As in many other series, these rare tumours were predominant on the left side (7/9) and affected mainly adult females (6/!) with a mean age of 44 years. The 8 secretory tumours were revealed by their hormonal effects: endocrine syndrome or arterial hypertension. The single, clinically non-secretory tumour presented as a palpable mass. The most common findings of hormonal exploration undertaken in 8 of the 9 patients were abolition of the cortisol nycthemeral cycle and non-response to dynamic tests. In 8 cases the tumour was demonstrated by intravenous urography, but its location and extension were best shown by CT scans. Two scintigraphies performed with labelled iodocholesterol were positive. All patients underwent complete excision of the tumour: 5 out of 9 had hepatic metastases at the time of surgery. The median survival of the 7 patients who died was 13 months; 6 of these had received Op'DDD (mitotane) post-operatively. Two patients, including one treated with Op'DDD, are still alive after 18 and 32 months respectively, without signs of recurrence.

ABH antigens are normally present at the surface of the healthy urothelium. In many cases of bladder tumours, the urothelium loses its antigens. While this loss would not seem to be associated with the grade or stage of the tumour, the persistence of the ABH antigens would seem to provide a more favourable prognosis.

The Döppler ultrasonic examination proposed for the diagnosis of acute painful scrotal syndromes has been used during 4 months. The presence of false negative results in the literature and in the series reported here throws some doubt on the reliability of the method and confirms that systematic surgical exploration remains imperative at the slightest doubt.

A series of 222 cases of adenocarcinoma of the kidney are discussed. Many of these cases involved extended carcinomas (stages III and IV, 65 p. cent; stage IV, 41 p cent). The surgical procedures used included 204 extended nephrectomies, 4 partial nephrectomies and 14 laparotomies for the exploration of unextirpable cancers. The mortality rate was 4.5 p. cent and the morbidity rate, 22 p. cent. 168 patients were followed up over a long period after an extended nephrectomy (8 died postoperatively and contact was lost with 28 patients after their operations). The 5-year survival rate was 71 p. cent for stage I, 77 p. cent for stage II, 48 p. cent for stage III and 23 p. cent for stage IV.

Seven patients with advanced testicular tumors, resistant to existing chemotheurapeutic agents, were treated with a new antitumor agent, the Cisplatinum (associated to mannitol induced hyperdiuresis). There were 3 objective remissions (1 complete and 2 partial). Major toxicity was gastrointestinal. There was little renal and hematologic toxicity in our serie. The drug may have use in combination therapy in advanced non seminomatous testicular tumors.

The aim of the present study is to analyse the response in patients with cancer of the urogenital region to a primary antigen 2-4 dinitrochlorobenzene (DNCB). A total of 69 patients with neoplastic disease were studied (13 cases with kidney cancer, 34 cases with bladder cancer, 13 cases with prostatic cancer, 5 cases with testicular cancer, one case with penis cancer, and 3 cases with cancer of the cervix, comparatively with 13 patients with non-malignant urological diseases. Whereas in the control group, 78% of the patients gave a positive skin reaction to DNCB, 15% of the patients with kidney cancer, 56% of the patients with bladder cancer, 69% of the patients with prostatic cancer and 60% of the patients with testicular cancer gave a positive reaction. If we consider the stages of the disease, the reaction was positive, in 91% of bladder cancer at stage I and in 47% at stages II and III in 100% of prostatic cancer at stage I and in 62% at stages II and III, in 60% of testicular cancer at stage IV (but 100% of seminomas and 0% of dysembryomas have a positive reaction). It would therefore seem that a correlation exists between the degree of the extension of the disease and the skin reaction to DNCB.