Medical undergraduates' self-evaluation: before and after curriculum reform.

BACKGROUND: In 2013, Taiwan launched a curriculum reform-the 7-year undergraduate medical education program was shortened to 6 years. This study explored the evaluation results from students regarding the curriculum reform and investigated graduates' perceptions regarding the curriculum organization of the two academic training programs affected by this curricular reform. METHODS: A cross-sectional survey was conducted from May 14 to June 12, 2019. The 315 graduates from both the 7-year and 6-year curriculum programs in the same medical school in Taipei were invited to participate in this study. In total, 197 completed questionnaires were received, representing a response rate of 62.5%. The results of the principal component analysis confirmed the validity of the constructs employed in this self-administered questionnaire. RESULTS: The t-test results yielded two main findings. First, the graduates from the 6-year program had significantly lower scores for preparedness for the upcoming postgraduate-year residency training than did their 7-year program counterparts. Additionally, the male graduates had significantly higher scores in terms of perceptions regarding curriculum organization and preparedness for postgraduate-year residency training than the female graduates. The results of stepwise regression also indicated that the sex difference was significantly correlated with graduates' readiness for their postgraduate-year residency training. CONCLUSION: To avoid sex disparities in career development, a further investigation of female medical students' learning environment and conditions is necessary. In addition to the cross-sectional study of students' perceptions, further repeated measurements of the objective academic or clinical performance of graduates in clinical settings are desirable.

Case study: international healthcare service quality, building a model for cultivating cultural sensitivity.

QUALITY PROBLEM OR ISSUE: In the context of medical tourism, cultural differences and language barriers are unneglectable factors, which compromise the shared decision-making between doctor and patients. INITIAL ASSESSMENT: This study constructs a cultural sensitivity cultivation (CSC) model that could be used to train medical professionals in the sector of medical tourism. CHOICE OF SOLUTION: Since 2016, there have been explorations in new strategies to offer better services. A critical step added is to include clients' perspectives in the re-examining process as a way to cultivate cultural sensitivity among the service providers. This practice expands to the sector of medical tourism. In our case study, we are able to conclude a new model that could yield quality international healthcare services. IMPLEMENTATION: The steps of our CSC model include (i) 'Promote Awareness' for shifting mindset, (ii) 'Share Scenarios' for developing empathy and compassion, (iii) 'Review Process' for collecting detail feedback, (iv) 'Identify Gaps' for targeting areas for improvement and (v) 'Improve Systems,' for changing standard operation procedures (SOPs) based on the strategies through Assmann's theory with a cultural-anthropological approach. EVALUATION: After Kuang Tien General Hospital (KTGH) implemented the new model for 1 year, the number of international patients has increased by 64%. More research could be done in the future to cover all the important aspects of providing international medical services and could apply the CSC model to different healthcare settings. LESSONS LEARNED: To optimize the shared decision-making between the doctor and medical traveler patients, healthcare providers should not only overcome language and cultural barriers but also should avoid unnecessary gestures in terms of status respect. Inviting patients to be co-investigator for quality improvement is a viable solution.

A meta-analysis of students' readiness assurance test performance with team-based learning.

BACKGROUND: Team-based learning (TBL) is increasingly being utilized across medical fields by engaging students in small group discussions. The readiness assurance test (RAT) is an essential feature that differentiates TBL from problem-based learning (PBL) activity sequences. No publication has discussed differences in the RAT in TBL in medical schools. The purpose of this meta-analysis study was to examine the performance of learners in terms of group RAT (GRAT) and individual RAT (IRAT) scores in TBL for students of healthcare professions. METHODS: Databases, including PubMed and Cochrane were searched using several terms. We assessed the quality of included studies and conducted a meta-analysis. RESULTS: In total, 11 studies with 1575 participants were identified. Quality assessment scores of these studies ranged 4 ~ 7. Mean GRAT scores were significantly higher than mean IRAT scores (standardized mean difference (SMD) = 2.027, 95% confidence interval (CI) = 1.657 ~ 2.486, p heterogeneity < 0.001). Although the test of subgroup differences was insignificant (p = 0.113), the nursing-only subgroup showed much better performance in the GRAT than the IRAT (SMD = 2.3CI: 95% CI = 2.0 ~ 2.6, I2 = 48.77%) compared to the others subgroup which included students from different majors. The subgroup analysis explained the heterogeneity in the overall analysis. Because of inadequate information from these 11 studies, a meta-regression could not explore the source of heterogeneity in terms of the mean age, duration of the intervention, preparation time before the RAT, and previous TBL experienced by students. CONCLUSIONS: Students achieved significantly higher scores for the GRAT than for the IRAT, especially the group which only included nursing students, which implies excellent collaboration in the group of nursing students.

Transcatheter arterial chemoembolization improves the resectability of malignant breast phyllodes tumor with angiosarcoma component: a case report.

BACKGROUND: A giant phyllodes tumor of the breast is a rare fibroepithelial lesion, and its treatment is controversial. Many case reports have reported performing skin graft reconstruction after tumor excision. Chest wall resection may be required if the tumor has invaded the chest muscle layer. We speculated that transcatheter arterial chemoembolization (TACE) can improve the resectability of malignant phyllodes tumor of the breast without requiring skin grafting. The English literature contains only one case report similar to our experience. CASE PRESENTATION: We report a rare case of a 51-year-old woman who had a giant malignant phyllodes tumor with heterologous sarcomatous differentiation in her right breast. The tumor was 19.43 × 12.98 × 21.47 cm. Whole-body computed tomography (CT) and bone scan did not reveal distant metastasis. Chest magnetic resonance imaging showed chest wall tumor invasion. Considering that skin defects after mastectomy can be extensive, we administered four courses of chemoembolization in the 5 weeks before surgery (30 mg of epirubicin and embozene microspheres [400, 500, and 700 µm]/week). Each process was well tolerated, with no serious complications. Only fever and local pain at the tumor site were noted, and these symptoms resolved with time. The follow-up CT scan showed a 45% reduction in tumor volume. Therefore, simple mastectomy was performed without skin grafting reconstruction. Wound healing was satisfactory, and the patient was discharged 1 week after surgery. Pathological and immunohistochemistry (IHC) findings showed a malignant phyllodes tumor with an angiosarcoma component. Because of tumor invasion of the chest wall, we recommended the patient receive radiotherapy, but she refused. Two months after surgery, recurrence of the malignant phyllodes tumor with right axillary lymph node involvement and lung metastasis was confirmed. CONCLUSION: Initial surgical resection of giant phyllodes tumors is often challenging. For initial presentation with unresectable giant phyllodes tumor, we recommend to perform TACE prior to surgery. In our patient, preoperative TACE was effective and safe. If the tumor has invaded the chest wall, early radiotherapy after surgery may be recommended for preventing recurrence.

Intestinal goblet cell carcinoid presenting with recurrent sterile peritonitis in a patient on peritoneal dialysis: a case report.

BACKGROUND: Goblet cell carcinoid is a rare variant of appendiceal carcinoid with mixed endocrine and exocrine features. The most common symptom and signs are abdominal pain, acute appendicitis and palpable mass. Additionally, abdominal pain is common in patient on peritoneal dialysis, which may confound the diagnosis in such patient. CASE PRESENTATION: We report a 71- years- old woman on peritoneal dialysis that experienced several episodes of abdominal cramping pain and sterile peritonitis. She had one episode of severe pain and underwent an appendectomy for suspicion of appendicitis. Goblet cell carcinoid was diagnosed. She had no further abdominal pain after she received appendectomy. CONCLUSIONS: Malignant dialysate was rarely reported in patient with peritoneal dialysis. However, goblet cell carcinoid can initially present with acute appendicitis, chronic intermittent abdominal pain and mimicking peritonitis. In systemically reviewing the literature, this is the first case report of sterile peritonitis with peritoneal dialysis caused by goblet cell carcinoid.

MCPIP1 suppresses hepatitis C virus replication and negatively regulates virus-induced proinflammatory cytokine responses.

Human MCP-1-induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase-1) plays important roles in negatively regulating the cellular inflammatory response. Recently, we found that as an RNase, MCPIP1 has broad-spectrum antiviral effects by targeting viral RNA. In this study, we demonstrated that MCPIP1 expression was induced by hepatitis C virus (HCV) infection in Huh7.5 hepatoma cells. MCPIP1 expression was higher in liver tissue from patients with chronic HCV infection compared with those without chronic HCV infection. Knockdown of MCPIP1 increased HCV replication and HCV-mediated expression of proinflammatory cytokines, such as TNF-α, IL-6, and MCP-1. However, overexpression of MCPIP1 significantly inhibited HCV replication and HCV-mediated expression of proinflammatory cytokines. Various mutants of functional domains of MCPIP1 showed disruption of the RNA binding and oligomerization abilities, as well as RNase activity, but not deubiquitinase activity, which impaired the inhibitory activity against HCV replication. On immunocytochemistry, MCPIP1 colocalized with HCV RNA. Use of a replication-defective HCV John Cunningham 1/AAG mutant and in vitro RNA cleavage assay demonstrated that MCPIP1 could directly degrade HCV RNA. MCPIP1 may suppress HCV replication and HCV-mediated proinflammatory responses with infection, which might contribute to the regulation of host defense against the infection and virus-induced inflammation.

Biomedical nanostructured coating for minimally invasive surgery devices applications: characterization, cell cytotoxicity evaluation and an animal study in rat.

BACKGROUND: Thermal injury and tissue sticking, which influence wound remodeling, are major concerns in electrosurgery. In this study, the effect of lateral thermal injury caused by different electrosurgical electrodes on hepatic remodeling was investigated. METHODS: A monopolar electrosurgical unit equipped with untreated stainless steel (SS) and chromium nitride coated stainless steel (CrN-SS) electrodes was used to create lesions on the liver lobes of adult rats. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days postoperatively. RESULTS: CrN-SS needles generated lower levels of sticking tissue, and the thermographs showed that recorded highest temperature in liver tissue from the CrN-SS needle group was significantly lower than in the SS needle group. The total injury area of livers treated with CrN-SS needles was significantly lower than livers treated with SS needles at each time point. Moreover, the CrN-SS needles caused a relatively smaller area of lateral thermal injury, a smaller area of fibrotic tissue, and a faster process of hepatic remodeling in rat liver than the SS needles. Immunofluorescence staining and Western blot analysis showed that rats treated with CrN-SS needles expressed lower levels of NF-κB and caspase-3 postoperatively. CONCLUSIONS: This study reveals that the plating of electrodes with a CrN film is an efficient method for improving the performance of electrosurgical units and should benefit wound remodeling. However, more tests must be performed to confirm these promising findings in human patients.

Effect of recombinant human bone morphogenetic protein-2 and Ling Zhi-8 on osteogenesis: a comparative study using a rabbit sinus model.

PURPOSE: This study evaluated the osteogenetic capability of Ling Zhi-8 (LZ-8; a protein purified from traditional Chinese medicine [lingzhi]) compared with recombinant human bone morphogenic protein-2 (rhBMP-2) in a standardized bony defect using a rabbit sinus model. MATERIALS AND METHODS: Twelve male New Zealand white rabbits (18 to 24 weeks old, 3.3 to 3.8 kg) were included in the study. Implants of normal saline 0.1 mg, rhBMP-2 0.1 mg, and LZ-8 0.1 mg were each mixed with a uniform biodegradable polyurethane-based material (Nasopore). The implants were inserted in a standardized bony defect of the nasal bone created by a 2.5-mm trephine bur. The rabbits were sacrificed at 1, 2, 4, and 8 weeks postoperatively. Volume computerized tomographic and histomorphometric examinations were used to evaluate the quantity and quality of regenerated bone. RESULTS: At postoperative week 4, radiography showed that the new bone volume was significantly larger in the rhBMP-2 group compared with the LZ-8 group (P = .041) and the control group (P = .015). Histomorphometrically, better wound healing of the rhBMP-2 group was found during the healing phase compared with the other 2 groups. CONCLUSION: The biomaterial implants using rhBMP-2 and LZ-8 had good biocompatibility and osteogenetic capabilities in the rabbit sinus model. Bone healing in rhBMP-2-treated defects was excellent and showed a significant difference compared with LZ-8. However, LZ-8-treated defects also exhibited bone regeneration, and this traditional Chinese medicine may possess osteogenic potential. Further investigations of the mechanism and application of this protein in osteogenesis are needed.

Cinnamic aldehyde, an anti-inflammatory component in Du-Huo-Ji-Sheng-Tang, ameliorates arthritis in II collagenase and monosodium iodoacetate induced osteoarthritis rat models.

Background and aim: Du-Huo-Ji-Sheng-Tang (DHJST) is a Chinese herbal formula used for arthralgia and arthritis treatment clinically. This study aims to evaluate the joint-protecting efficacy of DHJST and to identify the active constituents as the evaluation marker. Experimental procedure: DHJST can be categorized into three recipes: Blood-tonifying-herbs Si-Wu-Tang (SWT), Wind-dampness-dispelling-herbs (WDH) and Qi-tonifying-herbs (TH). All formulas were used to explore the joint-protecting efficacies. Results and conclusion: s: Firstly, DHJST could decrease the arthritis progression in the monosodium-iodoacetate-induced rat and cure arthritis in the type II collagenase-induced rat. Further, in lipopolysaccharide-stimulated RAW 264.7 cells, DHJST, TH and Cinnamomum cassia (CC), an ingredient in TH, were the most potent nitric oxide (NO) and prostaglandin E2 (PGE2) inhibitors. The major components, cinnamic aldehyde, showed the strongest NO and PGE2 inhibition. Up-regulated inducible NO synthase (iNOS) and cyclooxygenase-2 were inhibited by DHJST, TH, CC, and cinnamic aldehyde. In interleukin-1ß-stimulated primary chondrocytes, upregulated iNOS was inhibited by DHJST, TH, Cinnamomum cassia, and cinnamic aldehyde. Upregulated matrix metalloprotease-13 was only inhibited by DHJST and TH and Eucommia ulmoides (EU) extract. Results suggest that DHJST presented joint-protective and cure arthritis effects. TH presented equal joint-protective effects as DHJST. The major anti-inflammatory ingredient in TH was Cinnamomum cassia in TH. And cinnamic aldehyde was the potent anti-inflammatory active compound in Cinnamomum cassia. Therefore, this study may facilitate the modern use of DHJST with TH as a simplified version but equally effective anti-osteoarthritic agents with cinnamic aldehyde as a quality control marker of DHJST and TH in osteoarthritis prevention or treatment.

The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers.

Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p = 0.024, hazard ratio = 1.44 [1.05-1.99]). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression significantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p = 0.0035) and basal-like BCa tumours (p = 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001; Taipei Medical University [TMU] cohort, p < 0.001; Kaohsiung Veterans General Hospital [KVGH] cohort) or disease-free survival (p < 0.001 [TMU cohort], p = 0.034 [KVGH cohort]) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 [TMU cohort], p = 0.027 [KVGH cohort]), HER2 positive (p = 0.018 [TMU cohort], p = 0.037 [KVGH cohort]), and triple-negative (p = 0.013 [TMU cohort], p = 0.037 [KVGH cohort]) BCa. F11R-based RNA microarray analysis and Ingenuity Pathway Analysis were successful in profiling the detailed gene ontology of triple-negative BCa cells regulated by F11R. The EP300 transcription factor was highly correlated with F11R in BCa (R = 0.51, p < 0.001). By analysing these F11R-affected molecules with the L1000CDs datasets, we were able to predict some repurposing drugs for potential application in F11R-positive BCa treatment.

Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure.

8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case-control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose-response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p=0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC.

"Effects of high concentration oxygen treatment on traumatic pneumothorax in adult rabbits".

"We undertook this study to investigate the adequate oxygen concentration that can be applied safely to the treatment of pneumothorax. Complete unilateral pneumothorax was induced artificially in rabbits, which were subsequently treated with various inspired oxygen fractions (FIO2; 21%, 60%, 80% or 100%). The pneumothorax resolution time was measured together with the levels of IL-1ß and IL-8 in broncho-alveolar lavage (BAL) and plasma samples. Furthermore, the lungs from these animals were examined for histolopathological evidence of oxygen toxicity. The results showed that the resolution time was significantly faster in the pneumothorax rabbits when treated with higher FIO2. Significantly higher levels of IL-1 ß were detected in BAL samples collected from the pneumothorax-rabbits that had received FIO2 at levels of either 80% or 100% (P < 0.05), but not in those with FIO2 at the 60% level. However, there was no significant change in the level of IL-8 in the BAL when the pneumothorax-rabbits were treated with different FIO2 levels. In addition, no evidence of oxygen toxicity was found when the lung tissues were examined. The data indicated that higher FIO2 treatment can accelerate the resolution of pneumothorax, but caution should be exercised with regard to associated oxygen toxicity when the FIO2 used is greater than 80%. We conclude that treatment with 60% FIO2 is an appropriate concentration for oxygen therapy for the treatment of pneumothorax in this model."

miR-21 upregulation exacerbates pressure overload-induced cardiac hypertrophy in aged hearts.

Young and aging hearts undergo different remodeling post pressure overload, but the regulator that determines responses to pressure overload at different ages remains unknown. With an angiotensin II (Ang II)-induced hypertensive model, miR-21 knockout mice (miR-21-/-) were observed regarding the effects of miR-21 on hypertension-induced cardiac remodeling in young (12 week-old) and old (50 week-old) mice. Although the aged heart represented a more significant hypertrophy and was associated with a higher expression of miR-21, Ang II-induced cardiac hypertrophy was attenuated in miR-21-/- mice. Upon results of cardiac-specific arrays in miR-21-overexpressing cardiomyocytes, we found a significant downregulation of S100a8. In both in vitro and in vivo models, miR-21/S100a8/NF-κB/NFAT pathway was observed to be associated with pressure overload-induced hypertrophic remodeling in aged hearts. To further investigate whether circulating miR-21 could be a biomarker reflecting the aged associated cardiac remodeling, we prospectively collected clinical and echocardiographic information of patients at young (<65 y/o) and old ages (≥65 y/o) with and without hypertension. Among 108 patients, aged subjects presented with a significantly higher expression of circulating miR-21, which was positively correlated with left ventricular wall thickness. Collectively, miR-21 was associated with a prominently hypertrophic response in aged hearts under pressure overload. Further studies should focus on therapeutic potentials of miR-21.

Effect of urinary total arsenic level and estimated glomerular filtration rate on the risk of renal cell carcinoma in a low arsenic exposure area.

PURPOSE: We explored the relationship between urinary total arsenic and risk of renal cell carcinoma, and investigated whether having hypertension or a low estimated glomerular filtration rate would modify the risk of renal cell carcinoma. MATERIALS AND METHODS: The case-control study was conducted between November 2006 and May 2009 with 132 patients with renal cell carcinoma, and 260 sex and age matched controls from a hospital based pool. Pathological verification of renal cell carcinoma was completed by image guided biopsy or surgical resection of renal tumors. Urinary arsenic species, including inorganic arsenic, monomethylarsonic acid and dimethylarsinic acid, were determined with a high performance liquid chromatography linked hydride generator and atomic absorption spectrometry. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease Study equation. RESULTS: Urinary total arsenic was significantly associated with renal cell carcinoma risk in a dose-response relationship after multivariate adjustment. Low estimated glomerular filtration rate or hypertension was significantly related to renal cell carcinoma risk. Estimated glomerular filtration rate was significantly negatively related with urinary total arsenic. A significant interaction was seen between the urinary total arsenic and hypertension on renal cell carcinoma risk. The greatest odds ratio (6.01) was seen in the subjects with hypertension, low estimated glomerular filtration rate and high urinary total arsenic. A trend test indicated that the risk of renal cell carcinoma increased along with the accumulating number of these 3 risk factors (p <0.0001). CONCLUSIONS: Higher urinary total arsenic level was a strong predictor of renal cell carcinoma, and estimated glomerular filtration rate or hypertension interacts with urinary total arsenic in modifying the risk of renal cell carcinoma.

The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area.

Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG+GG genotype, in conjunction with high urinary total arsenic (≥14.02µg/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg(72)Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area.

Loss of p53 and MCT-1 overexpression synergistically promote chromosome instability and tumorigenicity.

MCT-1 oncoprotein accelerates p53 degradation by means of the ubiquitin-dependent proteolysis. Our present data show that induction of MCT-1 increases chromosomal translocations and deregulated G(2)-M checkpoint in response to chemotherapeutic genotoxin. Remarkably, increases in chromosome copy number, multinucleation, and cytokinesis failure are also promoted while MCT-1 is induced in p53-deficient cells. In such a circumstance, the Ras-mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase signaling activity and the expression of metastatic molecules are amplified. Given a p53-silencing background, MCT-1 malignantly transforms normal breast epithelial cells that are satisfactory for stimulating cell migration/adhesion and tumorigenesis. Detailed analyses of MCT-1 oncogenicity in H1299 p53-null lung cancer cells have shown that ectopically expressed MCT-1 advances xenograft tumorigenicity and angiogenesis, which cannot be completely suppressed by induction of p53. MCT-1 counteracts mutually with p53 at transcriptional levels. Clinical validations confirm that MCT-1 mRNA levels are differentially enriched in comparison between human lung cancer and nontumorigenic tissues. The levels of p53 mRNA are comparatively reduced in a subset of cancer specimens, which highly present MCT-1 mRNA. Our results indicate that synergistic promotions of chromosomal imbalances and oncogenic potency as a result of MCT-1 expression and p53 loss play important roles in tumor development.

Increased expression of enolase alpha in human breast cancer confers tamoxifen resistance in human breast cancer cells.

Enolase-alpha (ENO-1) is a key glycolytic enzyme that has been used as a diagnostic marker to identify human lung cancers. To investigate the role of ENO-1 in breast cancer diagnosis and therapy, the mRNA levels of ENO-1 in 244 tumor and normal paired tissue samples and 20 laser capture-microdissected cell clusters were examined by quantitative real-time PCR analysis. Increased ENO-1 mRNA expression was preferentially detected in estrogen receptor-positive (ER+) tumors (tumor/normal ratio >90-fold) when compared to ER-negative (tumor/normal ratio >20-fold) tumor tissues. The data presented here demonstrate that those patients whose tumors highly expressed ENO-1 had a poor prognosis with greater tumor size (>2 cm, *P = .017), poor nodal status (N > 3, *P = .018), and a shorter disease-free interval (<==1 year, *P < .009). We also found that higher-expressing ENO-1 tumors confer longer distance relapse (tumor/normal ratio = 82.8-92.4-fold) when compared to locoregional relapse (tumor/normal ratio = 43.4-fold) in postsurgical 4-hydroxy-tamoxifen (4-OHT)-treated ER+ patients (*P = .014). These data imply that changes in tumor ENO-1 levels are related to clinical 4-OHT therapeutic outcome. In vitro studies demonstrated that decreasing ENO-1 expression using small interfering RNA (siRNA) significantly augmented 4-OHT (100 nM)-induced cytotoxicity in tamoxifen-resistant (Tam-R) breast cancer cells. These results suggest that downregulation of ENO-1 could be utilized as a novel pharmacological approach for overcoming 4-OHT resistance in breast cancer therapy.

Pleomorphic hyalinizing angiectatic tumor of soft parts.

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a rare, nonmetastasizing tumor of uncertain lineage which was first reported in 1996. Here, we report a case of PHAT and review the literature. A 49-year-old man presented with a soft and progressively enlarging mass over the right buttock for several years. On suspicion that the mass was a right gluteal lipoma, he underwent surgical excision. The excised lesion measured 14 x 6 x 3.5 cm. It had a variegated appearance with a white-tan to yellowish color on the cut surface. Some punctate hemorrhage and vessel thrombosis were seen. Microscopically, the tumor was a PHAT characterized by clusters of ectatic, fibrin-lined, thin-walled vessels, which were surrounded by a mitotically inert, spindled, pleomorphic, neoplastic stroma that contained a variable inflammatory component. Immunohistochemical study showed that the tumor cells were positive for CD34, and negative for S-100, HMB45 and actin. The patient experienced local recurrence 6 months later. The recurrent tumor was widely excised. No evidence of metastasis was found during the 18 months after the second operation. The recurrent lesion had a microscopic appearance that was similar to the initial lesion.