See-Tong Pang

Total HLA class I loss in a sarcomatoid renal carcinoma cell line caused by the coexistence of distinct mutations in the two encoding β2-microglobulin genes

In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging to a sarcomatoid subtype, even following incubation with IFN-γ. β2-microglobulin (β2m) was not detected in RCC52 cells. Surprisingly, RCC52 cells harbor two mutations in the β2m genes in exon 1: a single G deletion (delG) in codon 6, which introduces a premature stop at codon 7, and a CT dinucleotide deletion (delCT), which leads to a premature stop at codon 55. Analysis of eight clonal sublines isolated from the RCC52 cell line showed that the two β2m gene mutations are carried separately by RCC52 cell subpopulations. The delG/delCT double mutations were detected in two sublines with a fibroblast-like morphology, while the delCT mutation was detected in the remaining six sublines with an epithelial cell morphology. Furthermore, loss of heterozygosity (LOH) of the β2m gene at STR D15S-209 was found only in the epithelioid subpopulation, indicating loss of one copy of chromosome 15. Immunostaining results of the tumor lesion from which the cell line RCC52 was originated were consistent with the phenotyping/molecular findings of the cultured cells. This is the first example of the coexistence of distinct β2m defects in two different tumor subpopulations of a RCC, where loss of one copy of chromosome 15 occurs in one of the subpopulations with total HLA class I antigen loss.

Prognostic value of TNM stage and tumor necrosis for renal cell carcinoma

Our objective was to assess the value of tumor necrosis and other factors for predicting the outcome of renal cell carcinoma (RCC). Our study comprised 328 RCC patients who were surgically treated at this hospital between 2001 and 2006. The five‐year survival data was analyzed using a Kaplan‐Meier statistical analysis. The prognostic factors were evaluated with a univariate analysis using a log‐rank test and multivariate analysis using the Cox proportional hazards regression method. The mean follow‐up period for these patients was 46.5 months (median 45.2 months). The univariate analysis revealed that age, tumor stage, TNM stage, grade, tumor necrosis, and histological type were statistically significant prognostic factors. The multivariate analysis showed that the TNM stage and tumor necrosis were the most important predictive factors in the patients overall survival. In the TNM stage with and without tumor necrosis, the five‐year overall survival rates in stages I + II were 80.5% and 89.2%, respectively (p = 0.115), where as the five‐year survival rates in stages III + IV were 32.7% and 84.0%, respectively (p < 0.001). Collectively, our present data revealed that tumor necrosis was an important predictive factor for survival in advanced stage RCC. In conclusion, both the TNM stage and tumor necrosis provided the most important prognostic factors of survival in RCC. Tumor necrosis proved to be a poor prognostic factor in advanced RCCs.

Urinary fluorescence in situ hybridization assay for detecting urothelial carcinoma in Taiwanese patients

Study Type – Diagnosis (case series)u2028Level of Evidenceu20034

Mixed germ cell tumor metastatic to the skin: case report and literature review.

BackgroundTesticular cancer is the most common cancer for males aged 15~35 years old. The initial presentation is typically an asymptomatic enlarged testicle. The retroperitoneum is the most common metastatic area. Other metastatic sites include the lung, liver, brain, adrenal glands, gastrointestinal tract and spleen. Skin metastasis is a rare event and frequently associated with poor prognosis.Case presentationA 19-year old male was diagnosed testicular mixed germ cell tumor with initial presentation of cutaneous metastasis at scalp and upper abdomen. After radical orchiectomy and four courses of cisplatin-based chemotherapy, the scalp and upper abdominal lesions regressed completely. The size of lung metastases remained unchanged.ConclusionsFor advanced stage testicular cancer, cisplatin-based chemotherapy is still effective to achieve partial response.

Effects of individual and partner factors on anxiety and depression in Taiwanese prostate cancer patients: A longitudinal study

Studies exploring the mediating and predictive factors of anxiety and depression for prostate cancer patients in Eastern countries are scant. Guided by the transactional model of stress and coping, this study determined the predictors and mediators of anxiety and depression in prostate cancer patients. The participants comprised 115 prostate cancer patients and 91 partners. The patients and partners completed questionnaires regarding physical symptoms, disease appraisals, coping behaviours, anxiety and depression in the period before confirmation of treatment decisions and 1, 3, 6 and 12xa0months after treatment. The results revealed that partner anxiety engendered a stressful situation and aggravated patient anxiety. Patients threat appraisals and affective-oriented coping behaviours mediated the relationships between their anxiety levels and those of their partners. The patients most recent prostate-specific antigen (PSA) levels and hormonal symptoms were key predictors of their anxiety and depression levels. The patients harm appraisals mediated the relationships between their most recent PSA levels and hormonal symptoms and depression. Their threat appraisals and affective-oriented coping behaviours mediated the relationships between their hormonal symptoms and anxiety and depression. To manage those key factors, reframing, appraising disease and improving coping behaviours may reduce anxiety and depression levels in prostate cancer patients.

Epstein-Barr virus DNA load in tumour tissues correlates with poor differentiation status in non-muscle invasive urothelial carcinomas

What’s known on the subject? and What does the study add?

Prostate cancer-specific anxiety and the resulting health-related quality of life in couples

AIMSnTo explore health-related quality of life (HRQOL) and its individual or mutual influences in people with prostate cancer and their spouses.nnnBACKGROUNDnFew studies have explored the influence of prostate cancer-specific anxiety of these people and their spouses on their individual or mutual HRQOL.nnnDESIGNnRepeated-measures design.nnnMETHODSnData on 48 dyadic of people and their spouses were collected from August 2015 - December 2016. Before the people treatment for prostate cancer, the first data collection occurred for the people and their spouses. The second to fifth data collections were conducted 6, 10, 18, and 24xa0weeks after the initial measurement. The variables concerned health status, marital satisfaction, positive affect, negative affect, prostate cancer-specific anxiety, and HRQOL. The Actor-Partner-Interdependence Model was adopted for data analysis.nnnRESULTSnThe people who had better physical HRQOL were those with good self-reported health status, higher positive affect and lower prostate cancer-specific anxiety. Better physical HRQOL was observed in the spouses who had good self-reported health status and had lower prostate cancer-specific anxiety. The people with localized cancer stages and lower negative affect had a better mental HRQOL. Better mental HRQOL was detected in spouses who had higher marital satisfaction, higher positive affect and lower negative affect.nnnCONCLUSIONnNurses can improve the HRQOL of people and their spouses by implementing activities that promote health and energy and reduce stress and by administering a mindfulness intervention.

Abstract 3780: Tumorigenicity and partial clear cell conversion of the epithelioid, but not fibroblastoid, subset of a sarcomatoid renal carcinoma cell line.

The biology of sarcomatoid renal cell carcinoma (RCC) and its conversion from and to the clear cell RCC cells are not fully understood. In this study, we analyzed the sarcomatoid RCC cell line, RCC52, derived from a clear cell RCC lesion with extensive sarcomatoid differentiation. When grown as monolayers, RCC52 cells consisted of mostly epithelioid cells and partly fibroblastoid cells, and were all PAX-2 negative, suggestive of in vitro growth of the sarcomatoid, but not clear cell, component. Immunohistology of xenografts resulted from subcutaneous injection of tumor cells revealed that only the parental line and all epithelioid sublines tested could develop solid tumors consisting of mostly sarcomatoid cells and PAX-2+ clear cells in areas. Our findings revealed (i) the coexistence of the two phenotypically distinct epithelioid and fibroblastoid subsets in this sarcomatoid RCC52 cell line, (ii) the dissociation of the abilities to display tumorigenicity and migratory/invasive potential by the epithelioid and fibroblastoid subsets, respectively, (iii) the capability of only epithelioid subset to undergo partial conversion to a clear cell type, and (iv) the identification of epithelioid subset as the niche for cancer stem cells within the RCC52 cell line. Importantly, using CD44 and CD24 markers in cytofluorometric analysis, we identified the phenotypes of the epithelioid and fibroblastoid subsets to be CD44+/CD24− and CD44+/CD24+, respectively. Collectively, our findings highlight the phenotypical and functional properties of the two distinct subsets in a sarcomatoid RCC. Thus, improved understanding of tumor heterogeneity, metastatic niche and stromal progression has profound consequence of metastatic disease, and promises to open up new strategies for therapy of cancer. Citation Format: Chin-Hsuan Hsieh, Hung-Chang Chen, Cheng-Keng Chuang, See-Tong Pang, Ying-Hsu Chang, Shuen-Kuei Liao. Tumorigenicity and partial clear cell conversion of the epithelioid, but not fibroblastoid, subset of a sarcomatoid renal carcinoma cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3780. doi:10.1158/1538-7445.AM2013-3780

Abstract 1358: Epithelioid and fibroblastic cell elements coexisting within the sarcomatoid renal carcinoma RCC52 cell line ensue divergent routes of tumor differentiation and progression

The immunobiology of sarcomatoid renal cell carcinoma and its transformation from and to the clear cell RCC cells are not fully understood. We analyzed a human sarcomatoid RCC cell line known as RCC52, derived from a primary lesion of clear cell RCC with extensive sarcomatoid differentiation. When grown as monolayers, RCC52 cells were all PAX-2 negative and consisted of mostly epithelioid cells and occasionally spindle/fibroblastic cells, suggestive of in vitro growth of the sarcomatoid, but not clear cell, component of the tumor. PAX-2 is a transcription factor found in all major RCC types including clear cell RCCs, but not in sarcomatoid RCCs. We next isolated and maintained a panel of epithelioid and fibroblastic clonal sublines. As determined by cDNA microarray analysis, cancer stem cell (CSC) marker genes, such as ALDH1L1, PSCA and ABCA2, were expressed greater in the epithelioid sublines, while mesenchymal-like cell marker genes including vimentin, snail, fibronectin and MMPs were expressed in much higher levels in the fibroblastic counterpart. Xenotransplantation in NOD/SCID mice showed that in contrast to fibroblastic sublines failing to developed tumors, epithelioid sublines invariably developed tumors at the injection sites. These results point to the existence of CSCs in the epithelioid, but not fibroblastic sublines. In order to investigate the self-renewal/colongenicity ability of these two types of clonal sublines, we used soft agar assay to assess their differential anchorage-independent colony forming abilities. Results showed the mean colony number in the parental RCC52 cells at day 28 was 293.3 ± 81.3 colonies/well, in the epithelioid sublines, the mean colony number was 322.2 ± 92.0 colonies/well. In contrast, no visible colonies were detected in any of the fibroblastic sublines tested. These results are consistent with those obtained in the xenotransplantation studies. Another important observation was that only epithelioid sublines developed xenografts in which clear cell component which was identified by its positive PAX-2 reactivity by immunostaining in some areas of tissue sections. Surprisingly, xenografts resulting from subcutaneous injection of RCC52 cells and the original patient tumor shared similar histopathology in that mostly sarcomatoid cells were noted with occasional clear cell areas. In conclusion, our results strongly point to the capability of sarcomatoid RCCs to undergo dedifferentiation or transdifferentiation. Further investigations into the molecular events responsible for sarcomatoid transformation from clear cell RCCs and for the progression of clear cell RCCs to sarcomatoid ones using additional tissues and cell lines of either types are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1358. doi:1538-7445.AM2012-1358

Abstract 4265: Identification of depressed HLA class I expression and CD44bright/CD24dim as the phenotype of floating but not adherent subpopulation harboring most tumor-initiating cells in the UP-LN1 carcinoma cell line

UP-LN1 is a poorly differentiated carcinoma cell line established from a lymph node (LN) metastatic lesion of the neck of a male patient with unknown primary. The CK7 − /CK20 + /CEA + /SCCA − phenotype detected in the original metastatic lesion and cultured cells led us to believe this cell line to be originated from a primary cancer of the gastrointestinal tract. UP-LN1 exhibited unique in vitro growth characteristics with naturally occurring floating (F) and adherent (A) cells. We hypothesize that the tumor-initiating cells (TICs) with cancer stem cell (CSC) properties may have differentially distributed in F and A cells of the UP-LN1 cell line contributing to cancer metastasis. We first made comparisons of TIC properties between F and A cells in terms of tumorigenicity in NOD/SCID mice. F and A cells were further examined for the expression of selected tumor markers and genes associated with TICs by DNA-microarray, RT-PCR and cytofluorometric analyses. Comparative sensitivities of the two cell types to cytolysis of non-MHC-restricted effector cells were also determined using 51 Cr release cytotoxicity assays. Results can be summarized as follows. (i) Injection of F cells at as low as 10 3 cells could initiate tumor formation in NOD/SCID mice, while an equivalent value for A cells was 10 5 . (ii) A panel of drug resistant gene mRNAs were tested, of which ABCG2, ABCA7, ABCB1, ABCC1 and ABCC4 were expressed in greater amounts in F cells as compared with A cells. (iii) F and A cells exhibited different phenotypes, CD44 bright /CD24 dim and CD44 dim /CD24 bright , respectively. (iv) Surface HLA class I expression was down-regulated in F cells, which could be restored after exposure to IFN-γ as low as 1 U/ml for 48 h. (v) F cells but not A cells exhibited extreme resistance to activated NK cells (CD56 dim /CD16 + cytotoxic subset) sorted out from peripheral blood mononuclear cells followed by IL-2 (100 U/ml, 72 h) activation. Moreover, F cells turned out to be highly sensitive to be modulated by IFN-γ to express CXCR4, a receptor of CXCL12. Up-regulation of surface CXCR4 expression with a concomitant down-regulation of cytoplasmic expression of CXCL12 was observed in F cells which are highly resistant to activated NK killing. Such modulation was found to be mediated via IFN-γ, a mediator which could be secreted by the immunomodulatory NK subset (CD56 bright /CD16 − ) within activated NK cell population. In summary, we have here identified resistance to activated NK killing, depressed HLA class I expression and CD44 bright /CD24 dim to be the phenotype of highly tumorigenic F cells, in which TICs/CSCs predominantly reside. IFN-γ-mediated induction of surface CXCR4 expression and enhancement of HLA class I expression in F cells might have occurred in the patient bearing UP-LN1 cells, resulting in invasive and metastatic events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4265.