PRMT1 is the predominant member of a family of protein arginine methyltransferases (PRMTs) that have been implicated in various cellular processes, including transcription, RNA processing, and signal transduction. It was previously reported that the human PRMT1 pre-mRNA was alternatively spliced to yield three isoforms with distinct N-terminal sequences. Close inspection of the genomic organization in the 5-end of the PRMT1 gene revealed that it can produce up to seven protein isoforms, all varying in their N-terminal domain. A detailed biochemical characterization of these variants revealed that unique N-terminal sequences can influence catalytic activity as well as substrate specificity. In addition, our results uncovered the presence of a functional nuclear export sequence in PRMT1v2. Finally, we find that the relative balance of PRMT1 isoforms is altered in breast cancer.
Breast cancer is the most common cancer in women, and lumpectomy is its first choice treatment. Therefore, the improvement of lumpectomy outcomes has a significant impact on a large patient population.
Background/Objective: Delays in times to surgery, chemotherapy, and radiotherapy impair survival in breast cancer patients. Neoadjuvant chemotherapy (NAC) confers equivalent survival to adjuvant chemotherapy (AC), but it remains unknown which approach facilitates faster initiation and completion of treatment. Methods: Women ≥18 years old with nonrecurrent, noninflammatory, clinical stage I-III breast cancer diagnosed between 2004 and 2015 who underwent both surgery and chemotherapy were reviewed from the National Cancer Database. Results: Among 155 606 women overall, 28 241 patients received NAC and 127 365 patients received AC. NAC patients had higher clinical T and N stages (35.8% T3/4 vs 4.9% T3/4; 14.4% N2/3 vs 3.7% N2/3). After adjusting for stage and other factors, NAC patients had longer times to begin treatment (36.1 vs 35.4 days adjusted, P = .15), and took significantly longer to start radiotherapy (240.8 vs 218.2 days adjusted, P < .0001), and endocrine therapy (301.6 vs 275.7 days adjusted, P < .0001).Unplanned readmissions (1.2% vs 1.7%), 30-day mortality (0.04% vs 0.01%), and 90-day mortality (0.30% vs 0.08%) were all low and clinically insignificant between NAC and AC. Conclusion: Compared to patients receiving AC, those receiving NAC do not start treatment sooner. In addition, patients receiving NAC do not complete treatment faster. Although there are clear indications for administering NAC vs AC, rapidity of treatment should not be considered a benefit of giving chemotherapy preoperatively. K E Y W O R D S breast cancer, cancer management, neoadjuvant chemotherapy, surgery | 2743 MELCHIOR Et aL.
A 79-year-old woman with atrial fibrillation, hypertension and hypothyroidism presented to the emergency department with syncope. She had previously experienced three minor syncopal episodes. A few months earlier, she had been prescribed rivaroxaban 15 mg/d after many years of warfarin therapy. On the day of presentation, she had woken feeling weak and fell to the floor, but managed to call 911. Following the initial assessment by emergency medical services she became unresponsive and briefly pulseless, and cardiopulmonary resuscitation was performed.In the emergency department, the patient was resuscitated with several boluses of normal saline, one unit each of packed red blood cells, platelets and prothrombin complex concentrate. Her vital signs stabilized. Diffuse abdominal guarding and tenderness were noted on examination. No prior intra-abdominal surgery was reported, and there was no definite antecedent infection.The patient's leukocyte count was 19.9 (normal 4.0-10.5) × 10 9 /L, plasma lactate level 12.4 (normal 0.5-2.2) mmol/L and hemoglobin 83 (normal 120-160) g/L; her hemoglobin level had been 121 g/L two months earlier. The international normalized ratio was 4.2 (normal 0.9-1.1). The platelet count and lipase level were within normal limits.Contrast-enhanced computed tomography (CT) showed a large intraperitoneal hematoma centred on a 3-cm pseudoaneurysm in the expected location of the pancreaticoduodenal arteries ( Figure 1). There were several smaller fusiform aneurysms arising from the celiac and superior mesenteric branch vessels. In the descending thoracic and abdominal aorta, there was an intramural hematoma, with active filling of multiple penetrating ulcerations ( Figure 2).Interventional radiology was consulted for angiography and potential transcatheter embolization. Angiography confirmed the CT findings, including a 3-cm pseudoaneurysm arising from the inferior pancreaticoduodenal artery. The artery was selected with a Progreat microcatheter (Terumo Interventional Systems), and the segments of the artery proximal and distal to the 3-cm ruptured pseudoaneurysm were embolized with five Nester embolization coils 3 mm × 14 cm (Cook Medical) and two Interlock embolization coils 3 mm × 12 cm (Boston Scientific) ( Figure 3).Angiography of the celiac and superior mesenteric arteries showed many smaller aneurysms involving several branch vessels. Given that these aneurysms were not easily accessible and did not meet the size criteria of 2 cm, they were not embolized. The interventional radiologist suspected vasculitis as the underlying cause. The smaller aneurysms were therefore expected to respond to medical therapy and did not require immediate intervention.Following endovascular coiling, investigations showed an increase in nonspecific inflammatory markers, including a C-reactive protein level of 180.1 (normal 0-1.0) mg/L and an erythrocyte sedimentation rate of 60 (normal 0-27) mm/h. Results of serologic evaluations were within normal limits, including tests for antineutrophil antibodies, anti-ex...
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