bims-myxlip Biomed News
on Myxoid liposarcoma
Issue of 2022–07–31
two papers selected by
Laura Mannarino, Humanitas Research
  1. ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.
  2. Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.
  1. Cancers (Basel). 2022 Jul 19. pii: 3509. [Epub ahead of print]14(14):
    ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.
    Elena Arconada-Luque, Jaime Jiménez-Suarez, Raquel Pascual-Serra, Syong Hyun Nam-Cha, Teresa Moline, Francisco J Cimas, Germán Fliquete, Marta Ortega-Muelas, Olga Roche, Diego M Fernández-Aroca, Raúl Muñoz Velasco, Natalia García-Flores, Cristina Garnés-García, Adrián Sánchez-Fdez, Sofía Matilla-Almazán, Víctor J Sánchez-Arévalo Lobo, Javier Hernández-Losa, Borja Belandia, Atanasio Pandiella, Azucena Esparís-Ogando, Santiago Ramón Y Cajal, Luis Del Peso, Ricardo Sánchez-Prieto, María José Ruiz-Hidalgo.
      Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.
    Keywords:  3-methyl-cholanthrene; ERK5; KLF2; MAPK7; leiomyosarcoma; rhabdomyosarcoma; soft tissue sarcoma
    DOI:  https://doi.org/10.3390/cancers14143509
  2. Br J Cancer. 2022 Jul 23.
    Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.
    Kazuhiro Tanaka, Ryunosuke Machida, Akira Kawai, Robert Nakayama, Satoshi Tsukushi, Kunihiro Asanuma, Yoshihiro Matsumoto, Hiroaki Hiraga, Koji Hiraoka, Munenori Watanuki, Tsukasa Yonemoto, Satoshi Abe, Hirohisa Katagiri, Yoshihiro Nishida, Akihito Nagano, Yoshiyuki Suehara, Hiroyuki Kawashima, Masanori Kawano, Takeshi Morii, Hiroshi Hatano, Junya Toguchida, Tomotake Okuma, Masanobu Takeyama, Satoshi Takenaka, Toshihiro Akisue, Taisuke Furuta, Makoto Emori, Toru Hiruma, Hidetatsu Outani, Tetsuji Yamamoto, Tomoko Kataoka, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto.
       BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS).
    METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS.
    RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD.
    CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk.
    CLINICAL TRIAL REGISTRATION: jRCTs031180003.
    DOI:  https://doi.org/10.1038/s41416-022-01912-5
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