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Background/aim: The tumor microenvironment (TME) is critical for tumor growth and progression. We report here an imageable model of the TME of orthotopic liver cancer., Materials and Methods: The transgenic red fluorescent protein (RFP)-expressing nude mouse was used as the host. The RFP nude mouse expresses RFP in all organs. Non-colored Huh-7 human hepatoma cells were injected in the spleen of RFP nude mice to establish an orthotopic liver cancer model. TME formation resulting from the orthotopic liver tumor was observed using the Olympus OV100 small animal fluorescence imaging system., Results: Non-colored liver cancer cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. RFP-expressing host cells and blood vessels were recruited by the liver tumors as visualized by fluorescence imaging. A desmin- and sirus-red-positive area increased around and within the liver tumor over time., Conclusion: These results indicate cancer-associated fibroblasts (CAFs) were recruited by the liver tumors suggesting that CAFs, along with the angiogenic tumor blood vessels, were necessary for liver-tumor growth and could serve as visible therapeutic targets., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Previous studies of long QT syndrome (LQTS) have revealed the presence of country-specific hot spots in KCNQ1 mutations, and the purpose of this study was to evaluate the influence of a common mutation on clinical phenotypes in Japanese LQT1 patients., Methods and results: We retrospectively studied the frequency of each mutation in 190 LQT1 Japanese probands and evaluated the clinical severity of LQT1 among carriers with a common mutation. We also compared it with that of carriers with other mutations. In the Japanese cohort, the most common mutation was p. A344spl (c.1032 G>A), comprising a substitution of a guanine for an adenine at the last base of exon 7, and it was found in 17 probands (8.9%). Regarding the clinical characteristics of A344spl carriers, the mean age-of-onset was 10±4 years, >40% were symptomatic, and the mean corrected QT interval was 461±30 ms. The prognosis for carriers of the A344spl mutation (n=31) was intermediate between that for the A341V mutation reported to be associated with severe phenotypes (n=24) and other mutations (n=290)., Conclusions: The A344spl mutation was a frequent LQTS genotype in Japan, which indicates that the influence of country-specific hot spots should be considered when studying LQT1 clinical phenotypes.

Primary uterine cervical neuroendocrine tumors are rare, but affect relatively young women and the prognosis is poor despite multidisciplinary treatment. The incidence of meningeal carcinomatosis arising from malignant tumors of the uterine cervix is extremely low, only two patients with meningeal carcinomatosis arising from a uterine cervical neuroendocrine tumor have been reported in the English literature. Moreover, there have been no reports in which this was confirmed at autopsy. We encountered a pregnant woman aged 33 years who was diagnosed as having atypical carcinoid of the uterine cervix after radical surgery. Despite multidrug chemotherapy (paclitaxel + etoposide + cisplatin and irinotecan + carboplatin), the patient developed multiple organ metastases. Although there was no metastasis to the brain parenchyma or the spinal cord parenchyma, the patient also developed meningeal carcinomatosis. Whole-brain radiation therapy was performed, but was ineffective. The patient died at 19 months after her initial operation and 10 days after diagnosis of meningeal carcinomatosis. The presence of meningeal carcinomatosis was confirmed at autopsy.

A group of 1196 type 2 (non-insulin-dependent) diabetic patients was followed for a mean of 10 years to determine the incidence of persistent albuminuria, its associated risk factors and prognosis, as well as causes of death in patients. None of the patients studied had albuminuria on entry. The mean annual incidence rate of persistent albuminuria per 1000 person-years in the patients was higher in males than in females (18.42 and 12.57, respectively). Development of persistent albuminuria was associated with age at entry, duration of known diabetes, systolic blood pressure, fasting glucose level, presence of diabetic retinopathy and type of treatment. Among 193 patients who developed persistent albuminuria during the observation period, 66 (34.2%) died before the end of the observation period, with a mean survival period (+/- SD) of 3.0 +/- 3.1 years after the onset of persistent albuminuria, indicating an extremely poor prognosis. Renal disease was the predominant cause of death in patients who developed persistent albuminuria, followed by heart disease and cerebrovascular disease.