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PURPOSE: The purpose of this study was to report experiences of practical heart sparing breast radiation therapy (RT) using continuous positive airway pressure (CPAP) in resource-limited radiation oncology clinics. PATIENTS AND METHODS: Twelve patients underwent computed tomography-simulations with both free-breathing (FB) and CPAP under the individual maximum tolerable air pressure. For each patient, left-sided breast RT plans (9 with breast only, 3 with breast and regional nodal stations) with FB and CPAP were created using 3-dimensional conformal RT (supine tangential or wide tangential RT fields) according to RTOG 1304. For daily RT, patients started CPAP in the patients waiting area for 15 minutes before entering the treatment room and continued CPAP during RT. Treatment setup times between breast RT with and without CPAP were compared. RESULTS: All patients tolerated CPAP well with 8 to 15 cm H2O of air pressure. Compared with FB, CPAP inflated the thorax and increased total lung volume by 35±16% (CPAP: 3136±751 vs. FB: 2354±657 cm, P<0.01); caudally displaced the heart by 1.8 cm (P<0.01); and decreased heart volume within tangential RT fields on computed tomography-simulation scans by 96±4% (1.4±2.5 vs. 21±17 cm, P=0.02) in all patients. Planning target volume coverage was acceptable in all RT plans. CPAP lowered mean dose (Dmean) to heart by 47±22% (2.5±1.5 vs. 5.4±3.3 Gy, P<0.01); heart volume receiving ≥25 Gy (V25) by 82±18% (2.2±2.6 vs. 9.1±7.1%, P<0.01); Dmean to left anterior descending coronary artery by 68±8% (4.7±1.9 vs. 14.8±3.3 Gy, P<0.01). CPAP decreased radiation dose to ipsilateral lung compared with FB: 9.1±5.8 versus 11.2±8 Gy (20% reduction, P=0.03) of Dmean; 15.7±12.5 vs. 20.5±17.5% (25% reduction, P=0.03) of V20. RT with CPAP did not increase treatment setup time compared with FB (week 1: 362±63 vs. 352±77 s; week 2 to 5: 217±13 vs. 201±14 s, all P>0.25). CONCLUSION: Novel use of CPAP allowed efficient and practical heart sparing breast RT without increasing infrastructural requirements in resource-limited radiation oncology clinics.

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Although surgery is the mainstay of local treatment for skin cancer, definitive radiation therapy (RT) has been also applied for patients who are unable to tolerate surgery. Definitive RT regimens usually consist of daily treatment for 4-7 weeks. Such protracted daily RT regimens, however, would not be feasible for non-compliant patients or patients who are unable to make multiple daily trips for weeks. Without treatment, however, skin cancers can continuously progress and cause distressing symptoms. A cyclical hypofractionated RT (QUAD Shot: 14 Gy in 4 fractions, twice-daily treatments with 6 hours interval on 2 consecutive days) can be a practical RT regimen for those patients. In this report, we present the successful treatment course of repeated QUAD Shots in a 79-year-old patient with neglected skin cancer that was disfiguring his face yet declined definitive surgery and protracted RT. We also evaluated and compared biologically equivalent doses between QUAD Shots and conventionally fractionated protracted RT regimens.

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Shikonin (SK), a natural naphthoquinone isolated from the Chinese medicinal herb, has been known to suppress the proliferation of several cancer cells. However, its role in the epithelial mesenchymal transition (EMT) has yet to be demonstrated. The aim of the present study was to examine the effects of SK on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. SK markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin in MDA-MB­231 cells, and increased the expression of E-cadherin in MCF-7 cells. SK also inhibited cell migration and invasion in vitro. The effects of SK on the LPS-induced EMT were mediated by the inactivation of the NF-κB-Snail signaling pathway. The results provided new evidence that SK suppresses breast cancer cell invasion and migration by inhibiting the EMT. Therefore, SK is a potentially effective anticancer agent for breast tumors, by inhibiting metastasis.

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Epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Prunella vulgaris (PV) inhibits the proliferation of various cancer cells; however, its possible role in EMT has not been demonstrated. In the present study, we explored the effect of PV aqueous extract (PVAE), a typical medicine for decoction, on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotype changes in cancer cell lines that enhanced cell migration and invasion. PVAE markedly inhibited these effects and produced accompanying changes in the expression of EMT markers, including decreased expression of N-cadherin and vimentin, and increased expression of ß-catenin. We found that PVAE effects on LPS-induced EMT were mediated by inhibition of the NF-κB/Snail signaling pathway. Our findings provide new evidence that PVAE suppresses cancer invasion and migration by inhibiting EMT. Therefore, we suggest that PVAE is an effective dietary chemopreventive agent with antimetastatic activity against malignant tumors.

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The epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Psoralea corylifolia L. (PC) inhibits the proliferation of various cancer cells. However, its possible role in EMT has not been identified. In the present study, we examined the effects of an aqueous extract of Psoralea corylifolia L. (PCAE), a typical medicinal decoction, on the EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. However, PCAE markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin and vimentin, and increased the expression of ß-catenin. PCAE also inhibited cell migration and invasion in vitro. The effects of PCAE on the LPS-induced EMT were mediated by the inactivation of the NF-κB-SNAIL signaling pathway. The results provide new evidence that PCAE suppresses cancer cell invasion and migration by inhibiting EMT. Therefore, PCAE is a potentially effective dietary chemopreventive agent for malignant tumors since it inhibits metastasis.

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Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy.

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OBJECTIVES: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk. METHODS: The authors searched MEDLINE, EMBASE, and Cochrane Library databases. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. RESULTS: Finally, a total of 11 studies encompassing 3588 recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T, and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an increased aGVHD risk (grade I-IV: OR, 2.722 (95% CI, 1.360-5.450); grade II-IV: OR, 2.265 (95% CI, 1.015-5.053)). Furthermore, patients who received grafts from donors with an IL-10 -819 CC genotype experienced more frequent grade I-IV aGVHD (OR, 2.306 (95% CI, 1.168-4.551)). Recipients with IL-10 -592 CC genotypes were at increased risk for grade II-IV aGVHD (OR, 1.999 (95% CI, 1.230-3.250)). Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms increased aGVHD risk. DISCUSSION AND CONCLUSION: This meta-analysis found the evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and donors increased the risk of aGVHD in allogeneic hematopoietic stem cell transplantation (HSCT) patients. These results contribute towards improving patient outcome through insight and rationale for individualized treatment strategies considering genetic determinants.

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