Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Crosstalk between progesterone receptor membrane component 1 and estrogen receptor α promotes breast cancer cell proliferation.

Progesterone (P4) and estradiol (E2) have been shown to stimulate and regulate breast cancer proliferation via classical nuclear receptor signaling through progesterone receptor (PR) and estrogen receptor α (ERα), respectively. However, the basis of communication between PR/ERα and membrane receptors remains largely unknown. Here, we aim to identify classical and nonclassical endocrine signaling mechanisms that can alter cell proliferation through a possible crosstalk between PR, ERα, and progesterone receptor membrane component 1 (PGRMC1), a membrane receptor frequently observed in breast cancer cells. While P4 and E2 treatment increased cell proliferation of ER+/PR+/PGRMC1 overexpressing breast cancer cells, silencing ERα and PR or treatment with selective estrogen receptor modulator (SERM) tamoxifen, or (PR-antagonist) RU-486 decreased cell proliferation. All four treatments rapidly altered PGRMC1 mRNA levels and protein expression. Furthermore, P4 and E2 treatments rapidly activated EGFR a known interacting partner of PGRMC1 and its downstream signaling. Interestingly, downregulation of ERα by tamoxifen and ERα silencing decreased the expression levels of PGRMC1 with no repercussions to PR expression. Strikingly PGRMC1 silencing decreased ERα expression irrespective of PR. METABRIC and TCGA datasets further demonstrated that PGRMC1 expression was comparable to that of ERα in Luminal A and B breast cancers. Targeting of PR, ERα, and PGRMC1 confirmed that a crosstalk between classical and nonclassical signaling mechanisms exists in ER+ breast cancer cells that could enhance the growth of ER+/PR+/PGRMC1 overexpressing tumors.

Superior Extended Nasal Myocutaneous Island Flap: An Alternative to Forehead Flap Reconstruction of the Nose.

Importance: Medium and large nasal defects are mostly addressed with paramedian forehead flap reconstruction. The superior extended nasal myocutaneous island (SENMI) flap offers an alternative that can be single stage and can avoid a gross deformity. Objective: To describe a new flap for nasal reconstruction of medium and large nasal defects and to define the flap's limitations and indications. Design, Setting, and Participants: This original study was a retrospective case series of patients who underwent SENMI flap reconstruction from 2008 to 2018 at a private tertiary referral center-Skin Cancer and Reconstructive Surgery Center (SCARS Center). Participants included all consecutive patients of the senior author who had undergone SENMI flap from September 2012 to December 2018, consisting of 53 patients. Indications for surgery were mostly skin cancer defects, postreconstructive, and post-traumatic deformities. IRB approval was obtained from the St. Joseph Health Center for Clinical Research. Main Outcomes and Measures: The location of the defects was defined. The vertical length of flap advancement was measured. Number of stages required to achieve functional and aesthetic goals was reported. Appearance rating after the first stage was assessed. Results: A total of 53 patients [mean age 68 (range 30-92) years; 26 (49%) female and 27 (51%) male] were included in the case series. Reconstructed areas included 8 in the upper two-thirds of the nose (dorsum and sidewall), 34 in nasal tip, 32 in nasal ala, 12 in soft tissue triangle and infratip, and 13 full thickness defects of the alar rim. The flap advancing distance defined the nature of flap mobility. Of 53 patients, 41 had up to 2.0 cm of flap advancement and 12 had 2.0 to 3.2 cm of advancement. Of 52 patients aesthetically evaluated, 43 had mild or no detectable shape deformity on photographic evaluation after one stage. Single stage was performed in 25 patients, two stages in 21 patients, and three stages in 7 patients. Functional nasal valve stenosis was present in 18 patients (33%) after one stage. Partial flap ischemia occurred in two patients (4%). Conclusions and Relevance: SENMI flap is an effective technique for nasal reconstruction. It offers a single- or two-stage alternative with less temporary deformity in comparison with forehead flap reconstruction.

The role of Drosophila mismatch repair in suppressing recombination between diverged sequences.

DNA double-strand breaks (DSBs) must be accurately repaired to maintain genomic integrity. DSBs can be repaired by homologous recombination (HR), which uses an identical sequence as a template to restore the genetic information lost at the break. Suppression of recombination between diverged sequences is essential to the repair of DSBs without aberrant and potentially mutagenic recombination between non-identical sequences, such as Alu repeats in the human genome. The mismatch repair (MMR) machinery has been found to suppress recombination between diverged sequences in murine cells. To test if this phenomenon is conserved in whole organisms, two DSB repair systems were utilized in Drosophila melanogaster. The DR-white and DR-white.mu assays provide a method of measuring DSB repair outcomes between identical and diverged sequences respectively. msh6(-/-) flies, deficient in MMR, were not capable of suppressing recombination between sequences with 1.4% divergence, and the average gene conversion tract length did not differ between msh6(-/+) and msh6(-/-)flies. These findings suggest that MMR has an early role in suppressing recombination between diverged sequences that is conserved in Drosophila.

Double-strand break repair assays determine pathway choice and structure of gene conversion events in Drosophila melanogaster.

Double-strand breaks (DSBs) must be accurately and efficiently repaired to maintain genome integrity. Depending on the organism receiving the break, the genomic location of the DSB, and the cell-cycle phase in which it occurs, a DSB can be repaired by homologous recombination (HR), nonhomologous end-joining (NHEJ), or single-strand annealing (SSA). Two novel DSB repair assays were developed to determine the contributions of these repair pathways and to finely resolve repair event structures in Drosophila melanogaster. Rad51-dependent homologous recombination is the preferred DSB repair pathway in mitotically dividing cells, and the pathway choice between HR and SSA occurs after end resection and before Rad51-dependent strand invasion. HR events are associated with long gene conversion tracts and are both bidirectional and unidirectional, consistent with repair via the synthesis-dependent strand annealing pathway. Additionally, HR between diverged sequences is suppressed in Drosophila, similar to levels reported in human cells. Junction analyses of rare NHEJ events reveal that canonical NHEJ is utilized in this system.