Hironori Tatsuki

KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients.

Karyopherin α 2 (KPNA2) is a member of the Karyopherin α family and has recently been reported to play an important role in tumor progression. The aim of the current study was to elucidate the clinicopathological significance of KPNA2 over‐expression in colorectal cancer (CRC).

Control of primary lesions using resection or radiotherapy can improve the prognosis of metastatic colorectal cancer patients.

Control of the primary lesions in metastatic colorectal cancer (mCRC) is still controversial. For rectal cancer patients, not only resection but also irradiation is expected to provide palliative effects. We investigated the effects of resection and irradiation of primary lesions (local control) on the prognosis of mCRC patients.

Anticancer effect of rapamycin on MCF-7 via downregulation of VEGF expression.

The importance of mTOR signaling in tumor biology is widely accepted and a number of agents that selectively target mTOR are being developed in cancer therapy. On the other hand, it has been demonstrated that mTOR can act as an angiogenic agent. Thus, we hypothesized that the mTOR inhibitor-induced anticancer effect is affected by expression of a key angiogenic factor, vascular endothelial growth factor (VEGF) and investigated the anticancer effect underlying mTOR using an in vitro assay. The mTOR inhibitor rapamycin dose-dependently reduced the cell viability of the breast cancer cell line, MCF-7, but did not reduce the cell viability of the colon cancer cell line, HT-29. Rapamycin reduced the VEGF expression in the culture medium of MCF-7, while rapamycin did not contribute VEGF expression in the culture medium of HT-29. VEGF stimulated cell viability and VEGF inhibition reduced cell viability of MCF-7, and rapamycin dose-dependently restored the cell viability of MCF-7 reduced by rapamycin. These findings suggest that mTOR acts as a direct anticancer agent and that the mTOR-inhibitor-induced anticancer effect involved the reduced expression of VEGF in MCF-7. Our results imply that mTOR regulates the expression of VEGF and is involved in breast cancer progression.

Establishment of a novel method to evaluate peritoneal microdissemination and therapeutic effect using luciferase assay

Peritoneal dissemination is a major cause of recurrence in patients with malignant tumors in the peritoneal cavity. Effective anticancer agents and treatment protocols are necessary to improve outcomes in these patients. However, previous studies using mouse models of peritoneal dissemination have not detected any drug effect against peritoneal micrometastasis. Here we used the luciferase assay to evaluate peritoneal micrometastasis in living animals and established an accurate mouse model of early peritoneal microdissemination to evaluate tumorigenesis and drug efficacy. There was a positive correlation between luminescence intensity in in vivo luciferase assay and the extent of tumor dissemination evaluated by ex vivo luciferase assay and mesenteric weight. This model has advantages over previous models because optimal luciferin concentration without cell damage was validated and peritoneal microdissemination could be quantitatively evaluated. Therefore, it is a useful model to validate peritoneal micrometastasis formation and to evaluate drug efficacy without killing mice.

A novel one-step lens cleaning device using air and water flow for endoscopic surgery

In a surgical operation requiring endoscopy, it is essential to obtain a clear endoscopic view. However, it is often disturbed by the contamination on the lens during the surgery. No device can clean the lens surface simply and completely. Many surgeons are hampered by the impaired view and the distraction by the repeated cleaning of the lens. Therefore, we developed a novel endoscope cleaning device to address this problem. The device was made of 3D-printed rubber-like plastic. It contains a syringe filled with saline and an aspiration system. It would be used intraoperatively to wash the lens surface in a few seconds with rapid flow of water and air. The cleaning ability of the device was evaluated using mayonnaise with adenosine triphosphate (ATP) as a model contaminant. The gauze-wiping maneuver was selected as control. After each maneuver, the clarity of the endoscopic view was evaluated, and residual contaminants were assessed quantitatively with ATP assay. The cleaning device obtained a crisp and clear view and eliminated the contaminant on the lens every time after a single cleaning maneuver. The gauze-wiping maneuver required for the lens to be wiped at least three times to obtain a clear view, and even then, some contaminants remained. Repeated contamination and cleaning using gauze led to accumulation of contaminants on the lens, which resulted in difficulty in cleaning the lens as the operation proceeded. The cleaning device did not show such accumulation. Our novel cleaning device with air and water flow has been shown to wash out the lens contaminants completely and immediately in a simple manner. It is expected to improve the safety and cost-effectiveness of endoscopic surgery.

Implication of atypical supraclavicular F18‑fluorodeoxyglucose uptake in patients with breast cancer: Association between brown adipose tissue and breast cancer

It has been reported that F18-fluorodeoxyglucose (FDG) uptake in the neck and supraclavicular lesions represents activated brown adipose tissue (BAT). In the present study, the association between BAT activity, detected by FDG-positron emission tomography (PET), and the clinicopathological features of patients with breast cancer was investigated. The cases of 156 consecutive patients with breast cancer who underwent FDG-PET preoperatively were analyzed. The distribution and intensity of atypical FDG uptake in the neck and/or supraclavicular region was reviewed. The intensity was graded as follows: 1, weak; 2, moderate; and 3, intense. Among the 156 patients, 70 (44.9%) exhibited grade 1 intensity, 65 (41.7%) exhibited grade 2 intensity and 21 (13.5%) exhibited grade 3 intensity. The intensity of FDG was significantly associated with human epidermal growth factor receptor 2 (HER2) expression and progesterone expression. Among the 156 patients, 6 (3.8%) had recurrent disease. Multivariate analysis revealed that showing a low grade of atypical FDG uptake was the only independent risk factor of short-term recurrence, and none of the patients with recurrent disease had atypical FDG uptake that may reflect the activation of BAT. These results indicated that the presence of BAT is associated with HER2 expression and the absence of BAT may be a prognostic factor for breast cancer.

18F‑fluorodeoxyglucose uptake as predictor for invasion in preoperatively diagnosed breast ductal carcinoma in situ: Significance in cases without mass formation

A diagnosis of ductal carcinoma in situ (DCIS) at needle biopsy often changes to that of invasive ductal carcinoma as the definitive pathological diagnosis following the surgical procedure. The present study sought to identify the factors associated with invasive disease in cases diagnosed as DCIS on needle biopsy by analyzing 18F-fluorodeoxyglucose-proton emission tomography (FDG-PET) findings. The present study retrospectively investigated the cases of 24 consecutive patients with primary breast cancer who were preoperatively diagnosed with DCIS by needle biopsy. The cases were divided into two groups based on the presence of invasion in the primary tumor. Among the 24 patients, 13 (54.7%) patients had invasive carcinoma and 11 (45.8%) had DCIS. The analysis revealed that the presence of FDG uptake in the tumor was the only independent predictor of presence of the invasive disease. No cases without FDG uptake exhibited invasion and all of these were ultimately diagnosed as DCIS. In the present study, all cases, including DCIS, with a nodular growth pattern demonstrated FDG uptake in the tumors, and all cases without FDG uptake were interpreted as having a diffuse growth pattern. The present findings suggested that the presence of FDG uptake in the tumor can be considered a predictor for invasion in cases with DCIS by needle biopsy, particularly in cases with a diffuse growth pattern. Patients preoperatively diagnosed as DCIS without mass formation and without FDG uptake in the tumor may avoid sentinel lymph node biopsy.