Mitochondria-targeted fluorescent polymersomes for drug delivery to cancer cells.

Mitochondria is an attractive target to deliver anticancer drugs. We have synthesized a cationic triphenylphosphonium ion conjugated fluorescent polymer which self-assembles into nanosized polymersomes and targets the encapsulated anticancer drug doxorubicin to cancer cell mitochondria.

The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology.

Spontaneously perforated pyometra: an unusual cause of acute abdomen and pneumoperitoneum.

Pneumoperitoneum is usually associated with gastrointestinal perforation or following surgical and endoscopic procedures. We report a rare case of spontaneously perforated pyometra presenting with generalised peritonitis and pneumoperitoneum. Perforation of the uterus is also unusual and often associated with the presence of an intrauterine device, a gravid uterus or malignancy. Our case illustrates the importance of clinical knowledge of acute and neoplastic gynaecological diseases, which are not uncommonly encountered by the general surgeon. Moreover, good appreciation of pelvic anatomy and close collaboration with gynaecology colleagues is essential as operative intervention is often required.

Prophylactic metoclopramide administered immediately after the induction of anesthesia has no effect on the incidence of postoperative emesis after strabismus surgery.

OBJECTIVE: To evaluate the efficacy of metoclopramide (0.25 mg/kg) administered IV immediately after induction of general anesthesia for the prevention of postoperative emesis in children undergoing, elective strabismus surgery. DESIGN: Double blind, randomized. SETTING: Operation-theater. SUBJECTS AND INTERVENTIONS: Seventy six non premedicated children of ASA class 1 and 2 were randomly allocated to receive either normal saline or metoclopramide immediately after the induction of general anesthesia. All children received a standardized similar anesthetic technique. Postoperative analgesia consisted of oral indomethacin. RESULTS: The incidence of postoperative emesis in the metoclopramide group was 60% versus 71% in a placebo group (p < 0.05). The incidence of severe emesis (2 or > 2 vomiting) was similar in the placebo group (34.20%) and metoclopramide group (21.05%). There were no adverse reactions like excessive sedation, extrapyramidal signs and hemodynamic depression in either placebo or metoclopramide group. CONCLUSIONS: Metoclopramide in a dose of 0.25 mg/kg administered intravenously prior to manipulation of eyeball is devoid of the effects but is not effective in preventing postoperative emesis in children undergoing strabismus surgery.