Cancer stem cells (CSC) or cancer stem cell-like cells (CSC-LCs) have been identified in many malignant tumors. CSCs are proposed to be related with drug resistance, tumor recurrence, and metastasis and are considered as a new target for cancer treatment; however, there are only a few reports on CSCs or CSC-LCs in renal cell carcinoma (RCC). Different approaches have been reported for CSC identification, but there are no universal markers for CSC. We used two different approaches, the traditional side population (SP) approach, and the enzymatic (aldehyde dehydrogenase 1 (ALDH1)) approach to identify CSC-LC population in two RCC cell lines, ACHN and KRC/Y. We found that ACHN and KRC/Y contain 1.4% and 1.7% SP cells, respectively. ACHN SP cells showed a higher sphere forming ability, drug resistance, and a slightly higher tumorigenic ability in NOD/SCID mice than Non-SP (NSP) cells, suggesting that cells with CSC-LC properties are included in ACHN SP cells. KRC/Y SP and NSP cells showed no difference in such properties. ALDH1 activity analysis revealed that ACHN SP cells expressed a higher level of activity than NSP cells (SP vs. NSP: 32.7% vs 14.6%). Analysis of ALDH1-positive ACHN cells revealed that they have a higher sphere forming ability, self-renewal ability, tumorigenicity and express higher mRNA levels of CSC-LC property-related genes (e.g., ABC transporter genes, self-replication genes, anti-apoptosis genes, and so forth) than ALDH1-negative cells. Drug treatment or exposure to hypoxic condition induced a 2- to 3-fold increase in number of ALDH1-positive cells. In conclusion, the results suggest that the ALDH1-positive cell population rather than SP cells show CSC-LC properties in a RCC cell line, ACHN.

Cancer stem cells (CSCs) or cancer stem cell-like cells (CSC-LCs) are a minority population of cells that relate to tumor progression, metastasis and drug resistance. To identify CSC-LCs in oral squamous cell carcinoma (OSCC), we used two OSCC cell lines, SAS and OSC20, and cell surface markers, CD44v3 and CD24. In addition, we examined CD44v3 and CD24 expression immunohistochemically and evaluated the relationship between the expression and clinicopathological parameters in 50 OSCC tissues. In SAS and OSC20, CD44v3+/CD24− cells showed a higher sphere forming ability than the other fractions, i.e., CD44v3+/CD24+, CD44v3−/CD24− and CD44v3−/CD24+ cells. The proportion of CD44v3+/CD24− cells in SAS and OSC20 was 10.7 and 24.1%, respectively. Regarding SAS, CD44v3+/CD24− cells also showed a higher drug resistance for CDDP, 5-FU and cetuximab and expressed higher mRNA levels of CSC property-related genes than the other cell fractions. The tumorigenicity of CD44v3+/CD24− cells was not significantly different from the other fractions in SAS. An immunohistochemical study revealed a significant correlation between CD44v3 expression in the invasive portion and lymph node metastasis. Kaplan Meier analysis revealed cases with CD44v3 expression in the invasive portion tended to show poor overall survival (OS) compared with those without CD44v3, and there was a significant difference in OS between CD44v3+/CD24− and CD44v3−/CD24− immunophenotypes in the invasive portion. In conclusion, the results suggest that the CD44v3+/CD24− cell population displays CSC-LC properties in a human OSCC cell line. Additionally, we present evidence that CD44v3 immunoexpression and CD44v3+/CD24− immunophenotypes could give prognostic information associated with unfavorable clinical outcomes.

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Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers.

Metastasizing pleomorphic adenoma (MPA) is the inexplicable metastasis of a histologically benign pleomorphic adenoma (PA). Approximately 50 cases have been reported. A 62-year-old woman noticed pain in the upper molar area. Her medical history included an operation for PA in the hard palate that was performed 20 years previously. On imaging, four relatively well-defined lesions were demonstrated in the maxillary bone. She underwent an operation for these lesions. Each lesion revealed the same histological features. Morphological findings displayed typical features of PA. Immunohistochemical staining showed that tumor cells of both primary and metastasizing lesions were positive for pleomorphic adenoma gene (PLAG) 1, which is a sensitive marker for PA. Gene fusions involving PLAG1 were examined by reverse transcription-polymerase chain reaction. However, no gene rearrangements of PLAG1 were found. We report here on a case of MPA in the maxillary bone, which appeared 20 years after resection of the primary tumor and review the relevant literature.

PurposeWe investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells.MethodsThe effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0–4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined.ResultsPEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control.ConclusionsAlthough in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a recently recognized inflammatory condition with single- or multi-organ involvement. The disease is characterized by tumefactive lesions with dense IgG4 plasmacytic infiltration (an elevated IgG4+/IgG+ cell ratio of > 40 %), storiform fibrosis, and obliterative phlebitis, with or without elevated serum IgG4 levels. The diagnostic criteria for IgG4-RD, proposed in 2011, were quite comprehensive and practical; however, it is important to remember that other diseases, such as hyper-interleukin (IL)-6 syndromes, may have common histopathological findings. Therefore, the histopathology of suspected IgG4-RD is occasionally not diagnostic. Here, we report a case of IgG4-related primary localized cervical lymphadenopathy without any other organ involvement. To our knowledge, there have been no previous reports of this. Additionally, the disease was associated with a 20-fold increase in IL-6 levels compared to that of the normal range.Case presentationWe report the case of a 52-year-old Japanese man who presented with a painless, somewhat diffuse swelling in the left submandibular region. Although the case fulfilled diagnostic criteria for IgG4-RD, the diagnosis was not straightforward due to abnormally high levels of serum IL-6. After systematic evaluation of the patient, a final diagnosis of IgG4-RD was established. Since then, a specialist in connective tissue disorders has evaluated the patient on a regular basis. Two years after his initial visit, no disease progress or systemic involvement has been noted.ConclusionWe present a case of an IgG4-related primary localized cervical lymphadenopathy mimicking hyper-IL-6 syndrome. This case can serve as an excellent reminder that the definitive diagnosis of IgG4-RD should be established using a systematic approach, in particular when it appears as an atypical manifestation.

Objective: Fluorescence visualization devices are screening devices that can be used to examine lesions of the oral mucosa non-invasively. We observed oral squamous cell carcinoma (OSCC) and leukoplakia using the IllumiScan (Shofu, Kyoto, Japan) fluorescence visualization device and examined its usefulness and characteristics.Methods: We investigated 31 OSCC and nine leukoplakia in patients who were examined using the IllumiScan and treated in our department from January 2017 to February 2018. Images taken with the IllumiScan were analyzed using image analysis software. We also examined the lesions using narrowband imaging (NBI). Additionally, the IllumiScan and NBI images and the non-stained areas of iodine staining method (IOM) were visually evaluated.Results: The average luminance of OSCC in the keratinized mucosa was significantly lower than that of OSCC in non-keratinized mucosa. The average luminance of OSCC was significantly lower than that of leukoplakia. Even in keratinized mucosa where IOM is impossible to use, the OSCC lesion exhibited fluorescence visualization loss.Conclusion: The application of the fluorescence visualization device to the oral mucosa may be useful for distinguishing between cancer and normal areas and can be used to detect OSCC in the keratinized mucosa. The use of the IllumiScan in combination with other conventional screening methods may lead to a better diagnosis.