RhoGTPase activation is a key step in renal epithelial mesenchymal transdifferentiation

ESRD is characterized by an interstitial infiltrate of inflammatory cells in association with tubular atrophy, epithelial mesenchymal transdifferentiation (EMT), and interstitial fibrosis. Human proximal tubular epithelial cells (HK2 cells) undergo EMT in response to activated PBMC conditioned medium (aPBMC-CM), showing acquisition of a fibroblastoid morphology, increased fibronectin-EDA (EDA) expression, loss of junctional E-cadherin localization, and cytokeratin 19 (K19) expression. The signaling pathway(s) that regulates EMT in response to aPBMC-CM is not well understood. This study shows that aPBMC-CM induces a rapid activation of RhoA, Rac1, and Cdc42 activity in HK2 cells from 15 min to 48 h. Moreover, infection with adenovirus expressing constitutively active RhoA, Rac1, and Cdc42 significantly increased the expression of EDA and downregulated expression of E-cadherin and K19. Dominant negative RhoA expression suppressed aPBMC-CM-induced upregulation of EDA but did not restore the expression of E-cadherin and K19. Constitutively active RhoA activated the Rho kinase and its downstream effectors, whereas constitutively active Rac1 and Cdc42 activated the P21-activated protein kinase in epithelial cells. In further experiments, HK2 cells were treated with toxin B, exoenzyme C3, Y-27632, and HA1077. These strategies, inhibiting the Rho/Rho kinase pathway, as well as the Rac1/Cdc42/P21-activated protein kinase pathway, blocked transdifferentiation of HK2 cells in response to aPBMC-CM. To conclude, these results indicate that aPBMC-CM activates RhoA, Rac1, and Cdc42 and their downstream effectors, leading to HK2 cells undergoing transdifferentiation. Therefore, activation of small RhoGTPases is a key step in the mechanism of EMT and likely to be a contributor to tubulointerstitial fibrosis.     

Three cases of pulmonary hamartoma appearing after radical nephrectomy for renal cell carcinoma

We report 3 patients with pulmonary hamartoma, all of whom had undergone nephrectomy for renal cell carcinoma. A lung tumor was detected 2 to 9-months following nephrectomy. Preoperative diagnosis was pulmonary metastasis from renal cell carcinoma and pulmonary tumor resection was performed in each case. There was a 9- to 12-month interval between the detection and resection of the lung tumor. The histological diagnosis of the lung tumor in all three patient was pulmonary hamartoma. Following the resection of the lung tumor, recurrence was not noted in any of the patients.     

Vitamin D3 treatment for locally advanced thyroid cancer: a case report

There are many intricacies in the surgical treatment of locally advanced thyroid cancer, including the medical management of the remaining functional organ and any cosmetic impairments, which are sometimes very difficult to manage and eventually carry a relatively high morbidity and mortality. Here, we report on a case of a 65-year-old female with an extremely locally-advanced thyroid cancer involving both lobes of the thyroid, blood vessels, trachea and esophagus. Despite the severity of her condition, oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years. Several reports have previously demonstrated the efficacy of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro, but clinical evidence has been limited so far. Therefore, this case report provides important evidence for the effectiveness of vitamin D3 therapy against advanced thyroid cancers.     

Nationwide survey on the treatment policy for well-differentiated thyroid cancer -- results of a questionnaire distributed at the 37th meeting of the Japanese Society of Thyroid Surgery

The treatment policy for patients with well-differentiated thyroid cancer varies among institutions. Although surgery has been the mainstay of treatment for this cancer, there is no consensus concerning the optimal extent of thyroid resection or the extent of lymph node dissection. Furthermore, controversy remains with regard to the indications for radiation therapy and hormonal therapy in surgical or non-surgical cases and the treatment modalities for cancer recurrence. To determine the actual status of treatment policies for thyroid cancer in Japan, a questionnaire was distributed to all physicians who participated in the 37th meeting of the Japanese Society of Thyroid Surgery, to inquire into treatment options for well-differentiated thyroid cancer in relation to clinical stages in actual situations. The replies to this questionnaire were analyzed in this study.