Investigator

Tatsuhiro Ohgami

Kyushu University

TOTatsuhiro Ohgami
Papers(2)
The BHLHE40‒PPM1F‒AMP…Safety evaluation of …
Collaborators(10)
Hideaki YahataHiroshi TomonobeHiroyuki KitaoIchiro OnoyamaKaoru OkugawaKazuhisa HachisugaKenzo SonodaKiyoko KatoMasafumi YasunagaEisuke Kaneki
Institutions(5)
Kyushu UniversityFukuoka Dental CollegeSaga UniversityKyushu University Bep…Kyushu Univeristy Hos…

Papers

The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer

BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity were observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) Ser293 and lactate dehydrogenase A (LDHA) Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.

Safety evaluation of abdominal trachelectomy in patients with cervical tumors ≥2 cm: a single-institution, retrospective analysis

For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. We attempted trachelectomy in 212 patients. Among the 135 patients with tumors <2 cm, trachelectomy was successful in 120, one of whom developed recurrence and none of whom died of their disease. Among 77 patients with tumors ≥2 cm, trachelectomy was successful in 62, 2 of whom developed recurrence and 1 of whom died of her disease. The overall relapse rate after trachelectomy was 1.6% (0.8% in <2 cm group and 3.2% in ≥2 cm group), and the mortality rate was 0.5% (0% in <2 cm group and 1.6% in ≥2 cm group). Recurrence-free survival (p=0.303) and overall survival (p=0.193) did not differ significantly between the <2 cm and ≥2 cm groups. Abdominal trachelectomy with intraoperative frozen sections of sentinel lymph nodes and cervical margins is oncologically safe, even in patients with tumors ≥2 cm.

2Papers
11Collaborators