Composition and epigenetic markers of heterochromatin in the aphid Aphis nerii (Hemiptera: Aphididae).

A detailed karyotype analysis of the oleander aphid Aphis nerii focusing on the distribution, molecular composition and epigenetic modifications of heterochromatin was done in order to better understand the structure and evolution of holocentric/holokinetic chromosomes in aphids. The female karyotype (2n = 8) consisted of 3 pairs of autosomes and a pair of X chromosomes that were the longest elements in the karyotype and carried a single, terminally located nucleolar organizer region. Males showed 2n = 7 chromosomes due to the presence of a single X chromosome. Heterochromatin was located in the X chromosomes only and consisted of 4 satellite DNAs that have been identified. A. nerii constitutive heterochromatin was enriched in mono-, di- and tri-methylated H3 histones and HP1 proteins but, interestingly, it lacked DNA methylation that was widespread in euchromatic chromosomal regions. These results suggest that aphid heterochromatin is assembled and condensed without any involvement of DNA methylation.

Phase II study of pegylated liposomal doxorubicin and oxaliplatin in relapsed advanced ovarian cancer.

OBJECTIVE: This phase II study evaluated the efficacy and safety of pegylated liposomal doxorubicin (PLD) 30 to 35 mg/m(2) plus oxaliplatin 70 mg/m(2) every 28 days in women with advanced ovarian cancer that recurred or progressed after a platinum-based regimen. METHODS: 43 women received a median of 6 courses of treatment. RESULTS: Objective response was 54% in the evaluable population and was higher in women with platinum-sensitive (67%) compared with platinum-resistant disease (29%). At a median duration of follow-up of 15.5 months, median overall survival was 15.8 months and time to tumor progression 7.3 months. Most toxicity was no greater than grade 1 or 2. There was no grade 3 or 4 palmar-plantar erythrodysesthesia. After 264 cycles administered, neutropenia was the most common cause of severe toxicity and required one patient to withdraw from the study. No cardiotoxicity was reported. CONCLUSION: PLD plus oxaliplatin is active and well tolerated in women with relapsed advanced ovarian cancer, regardless of platinum sensitivity.

A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission?

Objective. The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and/or overall survival in patients affected by epithelial ovarian cancer.Methods. A multicenter study examined 122 randomized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy (Adriamycin + Cyclophosphamide), PCy (Cisplatin + Cyclophosphamide), or Mitoxantrone + Carboplatin. Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil (FU) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days; the other 61 received no further treatment (nihil group).Results. Sixty patients in the Cisplatin arm were evaluable. There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm. Peritoneal relapses were 25% for Cisplatin treatment vs. 16.4 % for nihil. There were 29 deaths in the Cisplatin arm vs. 27 for nihil. Median overall survival time (95 months with Cisplatin vs. 96 months in the nihil group) and median disease-free survival (66 months with Cisplatin vs. 73 in the nihil group) were similar in both arms (p=0.66 and p=0.41, respectively). There were no significant differences in tumor stage and grade between the two arms. Seven patients presented a second neoplasm during follow-up: six in the nihil arm, but only one patient in the Cisplatin arm. Death in these patients was due to the second neoplasm and not to progression of ovarian cancer.Conclusion. Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival.

Elderly ovarian cancer: treatment with mitoxantrone-carboplatin.

OBJECTIVE: Data concerning optimal treatment of elderly patients with ovarian cancer are scanty. The management of ovarian cancer in the aged patient is many-sided: the diagnosis can be difficult and delayed, and aggressive surgery is often not attempted because of concomitant morbidity. We tested a combination of carboplatin and mitoxantrone potentially associated with low toxicity in elderly patients with ovarian cancer. METHODS: Eighty-two patients older than 70 years (median age, 75; range, 70-88) with epithelial ovarian cancer were referred to our multicenter group and enrolled into this pilot study. Carboplatin (JM8) was given at the dose of 230 mg/m2 and mitoxantrone at the dose of 9 mg/m2 every 28 days. RESULTS: Dose-limiting toxicity was represented by 4 cases of thrombocytopenia and 1 case of gastrointestinal toxicity. These 5 episodes occurred in 328 assessable cycles, representing a low toxicity profile (3%). Of the 68 assessable patients, 36 (53%) did not respond to chemotherapy (no change + progressive disease), complete response was observed in 15 (22%), and partial remission was observed in 16 (23.5%), accounting for an overall response rate of 45%. CONCLUSION: The carboplatin-mitoxantrone combination, at the dosage tested in this study, appears to be well tolerated by elderly patients with advanced ovarian cancer and is associated with an acceptable response rate. Optimally debulked patients also showed improved survival when compared with patients with more extensive tumor.

Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility.

During spermiogenesis, mammalian chromatin undergoes replacement of nuclear histones by protamines, resulting in a DNA that is highly condensed in the mature sperm. We have previously demonstrated that a percentage of human spermatozoa exhibit 1) positivity to the guanine-cylosine-specific chromomycin A3 (CMA3) fluorochrome and 2) the presence of endogenous nicks in their DNA. In situ protamination of mature human sperm limits the percentage of sperm positive to CMA3 and exhibiting endogenous nicks. In this study, we report further investigations that aim to clarify the relationship existing between levels of CMA3 stainability and the presence of endogenous nicks in the DNA of mature human spermatozoa. Human spermatozoa from 25 different samples showed values of sensitivity to the CMA3 fluorochrome ranging from 13% to 75%. The same samples showed a percentage of sensitivity to endogenous nick translation ranging from 1% to 38%. A strong correlation (r = 0.86) was evident between these two parameters. Prior staining of sperm with the CMA3 fluorochrome drastically reduced sensitivity to nick translation. In contrast, previously nick-translated sperm stained with CMA3 showed very little difference from samples that had not been pretreated. The presence of nicked sperm in the ejaculate may indicate anomalies during spermiogenesis and be an indicator of male infertility.

Continuous mitoxantrone infusion in pretreated epithelial ovarian cancer.

Mitoxantrone has shown moderate activity in advanced epithelial ovarian cancer following intermittent i.v. administration. Experiments and clinical data suggest that long-term continuous drug infusion may achieve a better therapeutic result with less toxicity. This hypothesis was tested in patients with advanced ovarian cancer who had been pretreated with other agents. Mitoxantrone was infused continuously in 21-day courses beginning every 6 weeks. If severe toxicity did not occur, the infusion rate was increased by 0.1-0.2 mg/m2 per day. The mitoxantrone solution proved to be stable over the 21-day infusion period. For ethical reasons an optimal two-stage design was employed. The trial was interrupted at the end of the first recruitment stage because the target of 3 responses out of 13 patients had not been achieved (only 1 patient had a partial response). Hematologic toxicity was observed in 11 patients, and 2 of them had a catheter occlusion. In conclusion, we found that 21-day of infusion of mitoxantrone apparently has no clinical benefit as compared with bolus administration in patients with advanced ovarian cancer.

Cytological and electrophoretic analysis of DNA methylation in the holocentric chromosomes of Megoura viciae (Homoptera, Aphididae).

Chromosomal and purified DNA methylation patterns were determined in the holocentric chromosomes of Megoura viciae by treatment with MspI and HpaII. Both enzymes produced a clear C-like banding pattern but widely digested one telomere of the X chromosome, which appeared as heterochromatic after C-banding treatment and brightly fluorescent after chromomycin A3 staining. Quantitative microfluorometric evaluations of DNA extraction performed on cytological preparations showed that both isoschizomers resulted in the same DNA extraction (about 30%). Contrary to what was found by in situ endonuclease treatment, the electrophoretic patterns of purified and digested DNA showed that digestion with MspI was slightly more extensive than that with HpaII in a zone of fragments ranging from 23 to 9 kb. This result indicates that aphid chromatin is not wholly unmethylated. The discrepancy between electrophoretic and cytological data has been explained by taking into consideration that DNA fragments with high molecular weights could be cleaved in situ by the enzymes but not extracted from the chromatin.

[Cefuroxime-tobramycin treatment of bacterial infections in cancer patients]. / Cefuroxim-tobramicina nelle infezioni batteriche dei pazienti neoplastici.

Twenty-five patients with different metastatic tumors, and often with other diseases which may have further compromised their defenses (such as diabetes, anemia and neutropenia), had a simultaneous bacterial complication. This was regarded as documented (i.e., proved by positive culture) in 12 of 25 patients, and probable if subjective and objective symptoms, X-ray, laboratory tests and the clinical picture agreed with bacterial infection in progress, even though the culture was negative, in 13 of 25 patients. Antibiotic therapy with cefuroxime-tobramycin gave good results in 19 of 25 patients, i.e., in 10 of 12 with a documented infection and in 9 of 13 with a probable infection. Fever of unknown origin and urinary infections were the most responsive to the therapy. Three of 25 patients had nephrotoxicity, with a very small rise in BUN and creatinine, which was easily reversible. According to our experience, antibiotic therapy with cefuroxime-tobramycin would be useful in cancer patients with bacterial complications because of its effectiveness and tolerability.