The telomere resolvase of the Lyme disease spirochete, Borrelia burgdorferi, promotes DNA single-strand annealing and strand exchange.

Spirochetes of the genus Borrelia include the tick-transmitted causative agents of Lyme disease and relapsing fever. They possess unusual genomes composed mainly of linear replicons terminated by closed DNA hairpin telomeres. Hairpin telomeres present an uninterrupted DNA chain to the replication machinery overcoming the 'end-replication problem' for the linear replicons. Hairpin telomeres are formed from inverted repeat replicated telomere junctions by the telomere resolvase, ResT. ResT uses a reaction mechanism similar to that of the type IB topoisomerases and tyrosine recombinases. We report here that ResT also possesses single-strand annealing activity and a limited ability to promote DNA strand exchange reactions on partial duplex substrates. This combination of activities suggests ResT is a nexus between the seemingly distinct processes of telomere resolution and homologous recombination. Implications for hairpin telomere replication and linear plasmid recombination, including antigenic variation, are discussed.

Are patients open to elective re-sampling of their glioblastoma? A new way of assessing treatment innovations.

BACKGROUND: This is a qualitative study designed to examine patient acceptability of re-sampling surgery for glioblastoma multiforme (GBM) electively post-therapy or at asymptomatic relapse. METHODS: Thirty patients were selected using the convenience sampling method and interviewed. Patients were presented with hypothetical scenarios including a scenario in which the surgery was offered to them routinely and a scenario in which the surgery was in a clinical trial. RESULTS: The results of the study suggest that about two thirds of the patients offered the surgery on a routine basis would be interested, and half of the patients would agree to the surgery as part of a clinical trial. Several overarching themes emerged, some of which include: patients expressed ethical concerns about offering financial incentives or compensation to the patients or surgeons involved in the study; patients were concerned about appropriate communication and full disclosure about the procedures involved, the legalities of tumor ownership and the use of the tumor post-surgery; patients may feel alone or vulnerable when they are approached about the surgery; patients and their families expressed immense trust in their surgeon and indicated that this trust is a major determinant of their agreeing to surgery. CONCLUSION: The overall positive response to re-sampling surgery suggests that this procedure, if designed with all the ethical concerns attended to, would be welcomed by most patients. This approach of asking patients beforehand if a treatment innovation is acceptable would appear to be more practical and ethically desirable than previous practice.

Fractionated Stereotactic Radiation for Central Nervous System Lymphoma: Retrospective Analysis of Initial Cases.

Primary central nervous system lymphoma (PCNSL) is primarily treated with combination chemotherapy, while whole-brain radiotherapy (WBRT) can be used as consolidative treatment or as a salvage option for central nervous system (CNS) relapse. We investigated whether fractionated stereotactic radiosurgery (fSRS) could replace WBRT in cases where patients had poor performance status or minimal disease at the time of consolidation, to spare patients the adverse effects of WBRT. We retrospectively identified 10 patients who completed 14 courses of fSRS for PCNSL or for CNS relapse of systemic lymphoma. Of 14 fSRS treatments, there were 10 distant brain recurrences among 6 patients, occurring on average 13.6 months after fSRS. A total of 4 of the 10 recurrences were treated with further fSRS, and 4 were treated with WBRT. There was one late in-field recurrence after both fSRS and WBRT, which occurred 27 months after fSRS. The median survival after fSRS was 36 months, and side effects after fSRS were minimal. This case series represents a potential treatment option for patients with CNS lymphoma, for whom WBRT is indicated but where the toxic effects of this treatment would be prohibitive.

Outcomes in Elderly Patients with Glioblastoma Multiforme Treated with Short-Course Radiation Alone Compared to Short-Course Radiation and Concurrent and Adjuvant Temozolomide Based on Performance Status and Extent of Resection.

(1) Background: Studies in elderly patients over the age of 65 with glioblastoma have shown survival benefits of short-course radiation therapy with concurrent and adjuvant temozolomide, making it the standard of care adopted at Juravinski Cancer Center. Our study retrospectively examines patients with GBM aged ≥ 70 at the JCC treated with short-course radiation alone compared to those treated with short-course radiation and concurrent and adjuvant TMZ, to determine if there is a difference in outcomes based on performance status. (2) Methods: A retrospective chart review was conducted at JCC using patients diagnosed with GBM in 2014-2017 (treated with the old protocol of short-course RT alone) versus those diagnosed in 2017-2019 (treated with the new protocol of short-course radiation and TMZ). Patient demographics, treatments, outcomes, and baseline KPS were analyzed. (3) Results: No clear benefit and more neurologic decline post treatment were seen in patients with borderline performance status and subtotal resection who underwent concurrent treatment with temozolomide and radiation. The addition of temozolomide was most helpful in patients with good performance status and a gross total resection. Variable outcomes were seen in patients with mixed traits. (4) Conclusions: This study suggests that performance status and extent of resection are significant determinants of patient response to treatment. In the case of elderly patients with borderline performance status and GTR or those with good performance status and STR, also described as "mixed traits", it may be beneficial to pursue single modality treatment, ideally based on MGMT promoter methylation status as opposed to bimodality treatment in order to maintain the best QOL.