Yohei Miyagi

Subsequent primary cancer incidence in cervical cancer survivors: insights from a comprehensive cohort study utilizing combined Japanese population-based cancer registries

This study aimed to evaluate the incidence of subsequent primary cancer (SPC) among cervical cancer survivors in Japan. Data from the cancer registries of Osaka, Kanagawa, and Miyagi prefectures were combined. The cohort included individuals diagnosed with invasive and in situ cervical cancer between 1980 and 2010, with the SPC incidence evaluated until 2015. The incidence and standardized incidence ratio (SIR) for different SPC sites were calculated. In addition, the association between SPC and radiotherapy was examined via competitive regression analysis. A total of 49,824 cervical cancer survivors were followed for up to 35 years, during which 4,507 (9.0%) of these survivors experienced SPC. Aside from the initial cancer, SPC was the most common cause of death among cervical cancer survivors. The most frequent SPC sites were the colorectal, breast, lung, and stomach, consistent with the frequency in the general population. A significant increase in the SIRs for bladder, lung, and colorectal cancers was observed (2.52, 1.63, and 1.44, respectively). Individuals who underwent radiotherapy had a higher risk of developing bladder cancer than those who did not, with a subdistribution hazard ratio of 2.28. The SIR for lung cancer significantly increased, particularly for the smoking-associated types, indicating the influence of smoking habits among survivors. Increased risk of specific SPCs was seen in both invasive and in situ cancer survivors. Cervical cancer survivors should be informed about the risks of SPCs and educated on the prevention methods. Our study provides valuable insights into specific actions SPC prevention.

Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer

The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed. We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed. We detected functional NKT and NKG2D LAG-3

Tissue factor pathway inhibitor-2 inhibits integrin β1 activation and focal adhesion formation and suppresses peritoneal ovarian cancer dissemination in mice

Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.