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Bone marrow-derived mesenchymal stem cells (MSCs) are able to migrate to tumors, where they promote tumorigenesis and cancer metastasis. However, the molecular phenotype of the recruited MSCs at the tumor microenvironment and the genetic programs underlying their role in cancer progression remains largely unknown. By using a three-dimensional rotary wall vessel coculture system in which human MSCs were grown alone or in close contact with LNCaP, C4-2 or PC3 prostate cancer cell lines, we established invitro matched pairs of normal and cancer-associated MSC derivatives to study the stromal response of MSCs to prostate cancer. We observed that prostate cancer-associated MSCs acquired a higher potential for adipogenic differentiation and exhibited a stronger ability to promote prostate cancer cell migration and invasion compared with normal MSCs both in vitro and in experimental animal models. The enhanced adipogenesis and the pro-metastatic properties were conferred by the high levels of IL-6 secretion by cancer-associated MSCs and were reversible by functionally inhibiting of IL-6. We also found that IL-6 is a direct target gene for the let-7 microRNA, which was downregulated in cancer-associated MSCs. The overexpression of let-7 via the transfection of let-7 precursors decreased IL-6 expression and repressed the adipogenic potential and metastasis-promoting activity of cancer-associated MSCs, which was consistent with the inhibition of IL-6 3′UTR luciferase activity. Conversely, the treatment of normal MSCs with let-7 inhibitors resulted in effects similar to those seen with IL-6. Taken together, our data demonstrated that MSCs co-evolve with prostate cancer cells in the tumor microenvironment, and the downregulation of let-7 by cancer-associated MSCs upregulates IL-6 expression. This upregulation triggers adipogenesis and facilitates prostate cancer progression. These findings not only provide key insights into the molecular basis of tumor-stroma interactions but also pave the way for new treatments for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone-like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin-regulatable hOC promoter for RCC-specific transcriptional targeting, and examined the anti-tumor effect of vitamins C and D3 with hOC-based adenoviral vectors towards RCC. Methods Real-time reverse transcriptase-polymerase chain reaction measured OC expression induced by vitamins C and D3, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC-cytotoxic effects of concomitant vitamins and hOC promoter-based adenoviral vectors, Ad-hOC-TK and Ad-hOC-E1, were evaluated in both cell culture and a xenograft murine model. Results We found that high doses of vitamin C induced H2O2-dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D3 treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co-administrated Ad-hOC-E1. Conclusions The results obtained in the present study demonstrate that vitamins C and D3 synergized with the anti-tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to investigate the chemopreventive effect of carotenoids on proliferating cell nuclear antigen (PCNA) and cyclin D1 expression in betel (Areca catechu) quid extract (BQE)-induced hamster oral cancer and human KB cell models, respectively. In the in vivo animal study, 41 hamsters were divided into six groups and treated with 0.3 ml of 0.5% 9,10-dimethyl-1,2-benz[a]-anthracene, BQE, α-tocopherol, β-carotene, lycopene, lutein and mixed carotenoids for 12 weeks. After treatment, the pouches were excised and graded using an immunohistochemical assay of PCNA. In the in vitro cell experiment, KB cells were cultured, and the inhibitory effect of carotenoids (β-carotene, lycopene and lutein) on cell proliferation was evaluated. Cyclin D1 and PCNA were evaluated in terms of cell differentiation. In the results, most of the animal lesions showed no overexpression of PCNA. However, in dysplastic lesions, PCNA expressions by the β-carotene, lutein, lycopene, mixed and vitamin E groups were less than that of the control group. In papilloma lesions, PCNA expressions by the β-carotene, mixed and vitamin E groups were less severe than that of the control group. PCNA expression by the vitamin E-treated group was less severe than that of the control group. No carcinoma was found in the lycopene or mixed groups. In the cell study, all carotenoids exerted a significant inhibitory effect on KB cell proliferation. Although lycopene suppressed KB cell proliferation at the G0/G1 phase with a significant decrease in PCNA expression, β-carotene and lutein possessed less of an inhibitory effect and even exhibited elevated cell proliferation at the G2/M phase. These results indicate that different carotenoids present various suppressive abilities against PCNA and cyclin D1 expressions in cell proliferation. In conclusion, carotenoids suppressed the carcinogenesis of induced hamster oral cancer and a cancer cell line by acting as a suppressor which inhibited the expressions of PCNA and cyclin D1. [Copyright &y& Elsevier]

Background: Although considered one of the most important prognostic factors for lung cancer patients, the health-related quality of life (HRQOL) of the newly diagnosed lung cancer population remains scarcely focused on in the literature. Therefore, we aimed to identify the determinants of HRQOL among newly diagnosed lung cancer patients in Taiwan., Methods: Two hundred and fifty patients newly diagnosed with lung cancer were recruited from a medical center in northern Taiwan through convenience sampling. Four structured questionnaires, including the Taiwanese version of the MD Anderson symptom inventory (MDASI-T), the Taiwanese version of the Pittsburgh Sleep Quality Index (PSQI-T), the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), were used to collect data. Further, a multivariate stepwise linear regression was conducted to determine the independent risk factors for HRQOL. A p value of less than 0.05 was considered statistically significant., Results: The patients (mean age was 61.04 years, 51.2% male, 94.0% non-small-cell lung cancer, 56.4% stage IIIB-IV) had moderate levels of HRQOL among the physical, psychological, social, and environmental domains, as well as overall QOL. HRQOL was not correlated with married status, religion, and comorbidity. Gender, age, family income, smoking status, cancer stage, ECOG PS scores, PA, symptom burden (severity and interference), and PSQI global scores were correlated with HRQOL. Notably, symptom severity was the dominant negative predictor affecting the psychological and environmental domains of QOL (β = -4.313 and -3.500, respectively), accounting for 23.2% and 14.6% of the variance, respectively. On the other hand, symptom interference was the dominant negative predictor affecting the physical and social domains of QOL, as well as overall QOL (β = -3.592, -1.984, and -0.150, respectively), accounting for 44.4%, 15.0%, and 24.1% of the variance, respectively., Conclusion: Newly diagnosed lung cancer patients suffered symptom severity and interference that significantly impaired their HRQOL; particularly, symptom interference affected the physical domain of QOL. Healthcare professionals should pay more attention to cancer-related symptom severity, symptom interference, and HRQOL changes when caring for newly diagnosed lung cancer patients., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

This chapter describes an efficient and reproducible method for large-scale propagation of Oncidium and Phalaenopsis protocorm-like bodies (PLBs) using floral stalk sections and seeds, respectively. The propagated PLBs can be used for Agrobacterium-mediated transformation. An advanced transformation system for Oncidium and Phalaenopsis orchids has been established. This protocol demonstrates that the time during which the PLBs are cocultivated with Agrobacterium is the key to promoting transformation efficiency. Modified DNA and RNA extraction methods are also provided to diminish polysaccharide contamination and to improve the quality for further molecular analysis.