Simultaneous mutations in SMN1 and SUMM2 fully suppress the dwarf and autoimmune phenotypes of Arabidopsis mpk4 mutant

Disruption of the Arabidopsis mitogen-activated protein kinase pathway, MEKK1–MKK1/MKK2–MPK4 (hereafter designated as MEKK1 pathway), leads to the activation of distinct NLRs (nucleotide-binding and leucine-rich repeat receptors), TNL (TIR-type NLR) SMN1, and CNL (CC-type NLR) SUMM2, resulting in dwarf and autoimmune phenotypes. Unlike mekk1 and mkk1mkk2 mutants, the dwarf and autoimmune phenotypes of mpk4 are only partially suppressed by the summ2 mutation, suggesting a significant contribution of SMN1 to the mpk4 phenotypes. However, full suppression of mpk4 by the smn1summ2 double mutation remains to be elucidated. To address this key question, we generated a mpk4smn1summ2 triple mutant and analyzed the dwarf and constitutive cell death phenotypes. The mpk4smn1summ2 triple mutant showed restoration of plant size with no detectable cell death, indicating full suppression of the dwarf and autoimmune phenotypes. These results suggest that SMN1 and SUMM2 constitute a robust surveillance system for the MEKK1 pathway against pathogen infection

Primary leiomyosarcoma of the inferior vena cava in a pediatric case: a case report and literature review

Abstract Background Leiomyosarcoma is classified as a soft tissue sarcoma. In adults, leiomyosarcoma is the most common malignancy affecting the vascular system; however, vascular leiomyosarcoma in children is extremely rare as most pediatric soft tissue tumors are rhabdomyosarcomas. The survival rate is very low, and incomplete resection is a poor prognostic factor. There is also a high rate of distant recurrence, with the lungs and liver being the most common sites of metastasis. There is no established effective chemotherapy, and complete surgical resection is the only potentially curative treatment for leiomyosarcoma. Case presentation A 15-year-old female patient with no significant medical history presented with severe upper abdominal pain and was admitted. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging showed a large retroperitoneal tumor protruding into the lumen of the inferior vena cava behind the liver and multiple small nodules, and metastasis to the liver was suspected. The tumor was 6 × 4 × 5 cm in diameter, located just behind the hepatic hilar structures, and was suspected to infiltrate into the right portal vein. The tumor was diagnosed as a leiomyosarcoma through an open tumor biopsy. As the multiple liver metastases were located only in the right lobe of the liver on imaging, we performed tumor resection with right hepatectomy and replacement of the inferior vena cava (IVC). The postoperative course was uneventful; however, on postoperative day 51, distant metastatic recurrences were found in the remaining liver and right lung. The patient was immediately started on chemotherapy and trabectedin proved to be the most effective drug in the treatment regimen; however, severe side effects, such as hepatotoxicity, prevented timely administration, and the patient passed away 19 months after surgery. Conclusions IVC resection and reconstruction combined with right hepatectomy were able to be safely performed even in a pediatric case. To improve the prognosis of leiomyosarcoma with multiple metastases, an effective treatment strategy combining surgical treatment and chemotherapy, including molecularly targeted drugs, should be established as early as possible