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This study aimed to investigate the effectiveness of neoadjuvant chemotherapy in patients with breast cancer in different age groups and evaluate the impact of age group on survival outcome according to different treatment responses. Data were retrospectively collected from the cancer registry database of Kaohsiung Medical University Hospital in Taiwan under an approved protocol. Overall, 96 elder patients (aged >50 years) and 96 younger controls (aged ≤50 years) who received neoadjuvant chemotherapy and breast surgical treatment were examined after 1:1 matching. Logistic regression analysis was used to investigate the effectiveness of treatment response in patients of different age groups. Additionally, the Kaplan-Meier estimator and log-rank test were performed to evaluate the effect of age group and treatment response on disease-free and overall survival (OS). Although no direct significant association was found between age group and treatment response, several significant results were found in treatment response stratification analysis. Among 16 pathological complete response (pCR) patients, elder patients showed significantly greater 5-year disease-free survival (DFS) than younger patients (DFS rate, 85.7% vs. 0%, p = 0.041). However, in 176 non-pCR patients, elder patients showed poor DFS compared to younger patients (DFS rate, 16.6% vs. 32.3%; log-rank test, p = 0.031). With limited sample size and study design, our study results demonstrate that patients aged >50 years who achieved pCR after neoadjuvant chemotherapy could obtain better survival outcome than younger patients. However, the younger patients showed no survival benefits regardless of pCR status.

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer., Breast cancer: gut microbes before and after menopause Women developing breast cancer before the menopause have less diverse gut microbe populations than their healthy peers, and significantly different gut microbial profiles than postmenopausal breast cancer patients. There is increasing evidence of a link between gut microbes and breast cancer, but most studies have focused on women after the menopause. The incidence of breast cancer in premenopausal women is increasing, especially in Asia. Researchers in Taiwan led by Chih-Po Chiang at Kaohsiung Medical University Hospital compared gut microbial populations in 267 breast cancer patients at different menopausal stages to matched controls. The results suggest that gut microbe profiling might offer a novel and noninvasive method for diagnosing and monitoring breast cancer. It may also lead to new strategies for prevention and treatment, as evidence emerges of a link between gut microbes and cancer.

Resistance to chemotherapy and hormonal therapy is a major clinical problem in breast cancer medicine, especially for cancer metastasis and recurrence. Di(2-ethylhexyl)phthalate (DEHP) affects drug resistance by an unknown mechanism of action. Here we analyzed breast cancer patients (N = 457) and found that Σ4MEHP (the sum of MEHP, MEHHP, MECPP and MEOHP concentrations) in urine was significantly higher (P = 0.018) in the recurrent breast cancer group compared with non-recurrent patients. Σ4MEHP-High was positively and significantly correlated with tumor stage (P = 0.005), lymph node status (P = 0.001), estrogen receptor status (P = 0.010), Her2/Neu status (P = 0.004), recurrence (P = 0.000) and tumor size (P = 0.002), as well as an independent prognostic marker (OR = 1.868; 95% CI = 1.424-2.451; P

Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues. Mitochondrial fractions were taken from four breast cancer tissues (luminal A, luminal B, Her2 –overexpression, and TNBC) and the expression of mitochondrial polyubiquitinated proteins was observed by western blot and ELISA. In addition, the expression of hsp10, hsp60, and clpp in mitochondria was observed by western blot in breast cancer tissues and adjacent tissues, and confirmed by ELISA. The expression levels of hsp10 and hsp60 were correlated with clinicopathological parameters in 114 breast cancer patients. We found an increase in the performance of mitochondrial polyubiquitinated proteins in breast cancer tissues of luminal A, luminal B, Her2-overexpression, and TNBC. The mitochondrial hsp10, hsp60, and clpp are abundantly expressed in breast cancer tissues rather than adjacent noncancerous tissues. The expression levels of mitochondrial hsp10 and hsp60 were highest in histological grade 3 breast cancer tissues. Additionally, mitochondria with high hsp60 expression were more present in Her2-positive tumors. We observed that mtUPR was specifically activated in breast cancer tissues but inactivated in normal mammary tissue. MtUPR had also exhibited a particular increase in Her2-overexpression tumors but not in ER- or PR-positive tumors. Taken together, we suggested that mtUPR may act as a potential candidate for developing novel Her2-overexpression breast cancer therapy.

NPWT fulfill graft taking in complex breast wounds., NPWT fulfill graft taking in complex breast wounds

Identifying and characterizing the interaction between risk factors for multiple outcomes (multi-outcome interaction) has been one of the greatest challenges faced by complex multifactorial diseases. However, the existing approaches have several limitations in identifying the multi-outcome interaction. To address this issue, we proposed a multi-outcome interaction identification approach called MOAI. MOAI was motivated by the limitations of estimating the interaction simultaneously occurring in multi-outcomes and by the success of Pareto set filter operator for identifying multi-outcome interaction. MOAI permits the identification for the interaction of multiple outcomes and is applicable in population-based study designs. Our experimental results exhibited that the existing approaches are not effectively used to identify the multi-outcome interaction, whereas MOAI obviously exhibited superior performance in identifying multi-outcome interaction. We applied MOAI to identify the interaction between risk factors for colorectal cancer (CRC) in both metastases and mortality prognostic outcomes. An interaction between vaspin and carcinoembryonic antigen (CEA) was found, and the interaction indicated that patients with CRC characterized by higher vaspin (≥30%) and CEA (≥5) levels could simultaneously increase both metastases and mortality risk. The immunostaining evidence revealed that determined multi-outcome interaction could effectively identify the difference between non-metastases/survived and metastases/deceased patients, which offers multi-prognostic outcome risk estimation for CRC. To our knowledge, this is the first report of a multi-outcome interaction associated with a complex multifactorial disease. MOAI is freely available at https://sites.google.com/view/moaitool/home.

Chemotherapy-induced peripheral neuropathy (CIPN) is considered one of the most common sequelae in patients with cancer who experience consistent abnormal sensations or pain symptoms during or after paclitaxel (PAC) chemotherapy. Transient receptor potential vanilloid 1 (TRPV1) and toll-like receptor 4 (TLR4) have been reported to interact in the nervous system in patients with CIPN. The antinociceptive effects of hyperbaric oxygen therapy (HBOT) on CIPN was demonstrated in this study through behavior tests. Using a CIPN rat model, we examined the effects of simultaneous HBOT (SHBOT) administration during chemotherapy and discovered that SHBOT achieved better reversal effects than chemotherapy alone. Twenty-four rats were randomly allocated to four groups: control, PAC, SHBOT, and HBOT after PAC groups. Behavior tests were performed to evaluate mechanical allodynia and thermal hyperalgesia status. Tissues from the spinal cord and dorsal root ganglions were collected, and TLR4 and TRPV1 expression and microglial activation were investigated through immunofluorescence (IF) staining. The mechanical and thermal behavior tests revealed that HBOT intervention during PAC treatment led to the early alleviation of CIPN symptoms and inhibited CIPN deterioration. IF staining revealed that TLR4, TRPV1, and microglial activation were all upregulated in PAC-injected rats and exhibited early and significant downregulation in SHBOT-treated rats. This study is the first to demonstrate that the use of SHBOT during PAC treatment has potential for the early suppression of CIPN initiation and deterioration, indicating that it can alleviate CIPN symptoms and may reverse CIPN in patients undergoing systemic chemotherapy.

The purpose of this study is to investigate the outcomes of an alternative method for large defects reconstruction after mastectomy by applying negative pressure wound therapy onto the grafts.

Colorectal cancer is a highly heterogeneous malignancy in the Asian population, and it is considered an important prognostic factor for baseline characteristics, tumor burden, and tumor markers. This study investigated the effect of baseline characteristics and tumor burden on tumor marker expression and progressive disease in colorectal cancer by using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and progressive disease status with a small sample of measurements and structural models. A total of 89 tissue samples of colorectal cancer were analyzed. Our results suggested that the expression of visceral adipose tissue-derived serpin (vaspin) is a potential indicator of colorectal cancer progression and may be affected by baseline characteristics such as age, sex, body mass index, and diabetes mellitus. Moreover, according to the characteristics of tumor burden, the expression of vaspin was generally higher in each progressive disease patient. The overall findings suggest that vaspin is a potential indicator of the progressive disease and may be affected by the baseline characteristics of patients.

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 &micro, mol/L, 40 &micro, L, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young&rsquo, s modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer in which several common diagnostic biomarkers are lost. Due to the loss of expression of receptors, treatment options for TNBC are limited. Therefore, finding safe and effective treatments for patients with TNBC is a major objective for clinicians. Previous studies suggested that cytokine-induced killer (CIK) cells may be beneficial for patients with a variety of tumor types. However, CIK therapy is not effective for all patients. In this study, we found that focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase that regulates several cellular functions in different cells, has the potential to regulate tumor cells sensitized to CIK cells. Knockdown of FAK expression in TNBC cells or the treatment of TNBC cells with a FAK inhibitor followed by coculture with CIK cells increases death of TNBC cells, suggesting that FAK plays important roles in sensitizing tumor cells to CIK cells. This phenomenon could be regulated by a FAK-programmed death-ligand 1 (PD-L1)-related mechanism. Overall, our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment, and show that CIK cell therapy combined with FAK inhibitors may be a novel therapeutic strategy for patients with TNBC.

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The lipid metabolic enzymes are considered candidate therapeutic targets for breast cancer. Long-chain acyl-coenzyme A (CoA) synthase (ACSL) is one of lipid metabolic enzymes and converts free-fatty acid to fatty acid-CoA. Five ACSL isoforms including ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6 are identified in human. High ACSL4 expression has been observed in aggressive breast cancer phenotype. However, the role of other isoforms is still little-known. We therefore, analyzed the expression of ACSL isoforms in each subtype of breast cancer within METABRIC dataset and cancer cell line encyclopedia dataset. The expression levels of ACSL1, ACSL4 and ACSL5 in estrogen receptor (ER)-negative group were higher than that in ER-positive group. Similar expression pattern was detected among breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Treatment of ACSL inhibitor triacsin C which inhibited enzyme activity of ACSL 1, 3, 4 and 5 suppressed cell growth of MCF-7 and MDA-MB-231. Our results further showed that high ACSL5 expression was associated with good prognosis in patients with both ER-positive and ER-negative breast cancer through KM plotter analysis. These results suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling pathways and ACSL5 is a potential novel biomarker for predicting prognosis of breast cancer patients.

Stereotactic vacuum‐assisted biopsy (SVAB) is an alternative method of breast biopsy for nonpalpable lesions detected by mammography. Considering the diagnostic effectiveness, a direct comparison of SVAB and open surgical biopsy (OSB) is lacking. We performed a retrospective review of 276 (33.8%) SVAB and 541 (66.2%) OSB to compare the diagnostic accuracy and the total number of procedures the patients underwent. The negative predictive values of OSB and SVAB were 99.77% and 99.61%, and their false‐negative rates were 0.96% and 4.76%, respectively. SVAB, as the first‐line biopsy method, obviated 92.3% of operations. All malignancies diagnosed using SVAB could be treated with single therapeutic surgery. By contrast, 48% of malignancies of OSB group received two operations. Breast Imaging Reporting and Data System (BI‐RADS) category used at the study correlated well with the percentage of malignancy and can thus be used to predict biopsy results. Our study concluded that SVAB is reliable for diagnosing nonpalpable breast lesions and is the better biopsy method for categories 3 and 4A lesions, which reduces the benign surgery rate. For lesions with a higher likelihood of malignancy, BI‐RADS 4B, 4C and 5, SVAB has an advantage over OSB, which lowers the total number of operations for malignancy treatment.

Fatty acid metabolism is important in the regulation of breast cancer progression. Some of the proteins involved in fatty acid transport have been demonstrated to promote the proliferation, migration, and invasion in breast cancer cells. Solute carrier family 27 member 4 (SLC27A4) is a fatty acid transporter protein and is related to very long chain acyl-CoA synthetase activity. In the present study, bioinformatic analysis revealed that relatively high SLC27A4 expression was observed in all subtypes of breast tumor tissues when compared to normal breast tissues. Silencing SLC27A4 expression significantly reduced uptake of free fatty acids in two breast cancer cell lines, Hs578T and MDA-MB-231. Cell growth inhibition was observed in SLC27A4-silenced Hs578T and cell cycle was arrested at G2/M. In addition, the capacity of migration and invasion decreased in both cell lines after knockdown of SLC27A4. The epithelial&ndash, mesenchymal transition signaling pathway was inhibited because protein expression of Slug, vimentin, &alpha, smooth muscle actin, and other regulators was lower than that in control cells. Taken together, our results confirm that high SLC27A4 is associated with tumor progression in breast cancer cells. It is worth investigating whether SLC27A4 serves a diagnostic marker and therapeutic target in further studies.

Purpose To examine the potential cost-savings of stereotactic vacuum-assisted biopsy (SVAB) over open surgical biopsy (OSB) in diagnosis of nonpalpable lesions on mammography and to estimate the cost-saving effect on lesions at different levels of malignant probability. Methods This retrospective study was approved by our Institutional Review Board. We retrospectively reviewed 276 (33.8 %) SVAB and 541 (66.2 %) OSB medical records at a medical center. Direct costs included patients’ self-paid and national health insurance claim charges. Indirect costs were calculated using sick days, average salary, and age-adjusted employment rate. One-way and two-way sensitivity analyses were conducted. Lesion classification was determined by the assessment categories of Breast Imaging Reporting and Data System (BI-RADS), 4th or 5th editions. Results SVAB decreased the direct cost by $90.3 (10.1 %) per diagnosis. The indirect cost was decreased by $560.2 (96.0 %). Overall, SVAB saved 43.9 % of resource utilization for each biopsy. Taking the cost of the subsequent malignant surgery into account, from the healthcare providers’ perspective, SVAB was cost-effective if a lesion had less than 19 % likelihood of malignancy. From the societal perspective, SVAB reduced productivity loss for all the lesions. Based on the positive predictive value of the BI-RADS categories, SVAB was more suitable for the lesions of category 4A and category 3, resulting in greater savings in both medical and societal resources. Conclusions SVAB is a cost-effective diagnostic option for nonpalpable breast lesions. The cost-saving effect is greater for the lesions of category 4A and category 3.

Long-chain fatty acids are the most abundant fatty acids and are essential for various physiological processes. Translocation of long-chain fatty acids across cell membrane is dependent on transport proteins. Solute carrier family 27 member 6 (SLC27A6) is a transport protein which mediates long-chain fatty acid uptake. The bioinformatic analysis revealed that the expression of SLC27A6 in non-tumoral breast tissue was higher than that in tumoral breast cancer in clinic samples. When SLC27A6 expression in non-tumorigenic cell H184B5F5/M10 was repressed, the fatty acids uptake capacity and cell proliferation was inhibited, and cell cycle was delayed. The protein expression of cell cycle regulators including cell division protein kinase 4 (CDK4), CDK6, and cyclin D1 was significantly decreased in SLC27A6-silenced H184B5F5/M10. By contrast, relatively low SLC27A6 expression in tumorigenic breast cancer cell Hs578T when compared to H184B5F5/M10. Repressing SLC27A6 expression did not affect these phenotypes in Hs578T. The interaction network of SLC27A6 was further investigated via STRING database. The function of these SLC27A6-associated proteins mainly involved in lipid biosynthesis, fatty acid metabolic process, and fatty acid transport. In conclusion, this study reveals inverse correlation between SLC27A6 expression and tumoral tissues and provides a new insight into SLC27A6-mediated cell growth and cell cycle regulation in non-tumorigenic breast cells.

Purpose The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. Methods This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. Results The survival rate at 24 months was 57.2% (95% CI 51.0–62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45–3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients’ tumors with the luminal A subtype had a significantly better objective response rate. Kaplan–Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p

A disintegrin and metalloproteinase domain 33 (ADAM33) gene is a transmembrane glycoprotein that mediates changes in cell adhesion and plays an important role in cancer progression. Since bisphenol A (BPA) and phthalates are epigenetically toxic, the purpose of this study was to examine whether BPA and phthalate metabolites, including monoethyl phthalate (MEP), mono‑n‑butyl phthalate (MBP), mono‑isobutyl phthalate (MIBP), mono(2‑ethylhexyl) phthalate (MEHP), mono(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP), mono(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP), and mono(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP), have an epigenetic impact on ADAM33 and the incidence of breast cancer. CpG islands of breast cancer microarray datasets obtained from the Gene Expression Omnibus (GEO) were used to assess the ADAM33 methylation profile. We designed a case‑control study including 44 cases and 22 age‑matched controls to detect the methylation status of intron 1 in ADAM33 from peripheral blood mononuclear cells (PBMCs) in blood, using BSP, nested PCR, and bisulfite sequencing, and measured the in vivo gene expression of ADAM33 and the urinary concentrations of endocrine‑disrupting chemicals (EDCs), using real‑time PCR, high‑performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC‑MS). Only one dataset, GSE32393, reached significance (P=0.016). ADAM33 expression and methylation frequencies at CpG site 3 in intron 1 were higher in the control group. We found a positive association between intron 1 methylation level and ADAM33 expression as well as urinary concentrations of MEHHP, MECPP, MEOHP and Σ4MEHP (the sum of MEHP, MECPP, MEHHP, and MEOHP) in the cases. This study suggests that metabolites of phthalate such as MEHHP, MECPP, MEOHP and Σ4MEHP may increase the intron 1 methylation level to elevate ADAM33 gene expression and have a protective effect on reducing the risk of breast cancer.

In the tumor microenvironment, soluble molecules play important role in the establishment of a pre-metastatic niche. The S100 calcium-binding protein family are inflammatory molecules that contribute to the development of a pro-inflammatory tumor microenvironment. S100B belongs to the S100 family and serum S100B (also known as S100beta) serves as a marker for metastasis in lung cancer, ovarian cancer and melanoma. However, the association between S100B and the metastasis of breast cancer is not yet well understood. In the present study, a relatively low S100B expression was observed in the tumor samples compared to normal breast tissue among online microarray datasets. When the estrogen receptor (ER)-negative breast cancer cell lines, MDA-MB-231 and Hs578T, were treated with recombinant human S100B, cell migration was significantly inhibited and epithelial cadherin expression was increased. Our results revealed that a high S100B expression predicted a good overall survival in patients with ER-negative breast cancer, and good distant metastases-free survival in all patients with breast cancer via the analysis of the KM plotter and SurvExpress databases. Although previous studies have indicated that the interaction of S100B with wild-type p53 inhibits p53 function, a high S100B expression is associated with a good prognosis in patients with p53 mutant and p53 wild-type breast cancers. On the whole, our findings demonstrate that S100B treatment suppresses the migratory capacity of ER-negative breast cancer and that S100B expression may serve a predictive marker for metastasis in breast cancer.

Tumor-associated dendritic cells (TADCs) are important in tumor immune surveillance, and it has been reported that the secretion of interleukin (IL)-10 by cancer cells is a major factor involved in the induction of TADCs in the tumor microenvironment. In the present study, IL-10 was found to activate cluster of differentiation (CD)45 protein tyrosine phosphatase (PTPase), inducing a TADC-like phenomenon. The PTPase inhibitor, phenylarsine oxide, and a CD45 inhibitor reversed the IL-10-induced impaired differentiation of the DCs, and also reversed the induction of the TADCs by A549, MDA-MB-231 and SW480 conditioned media, which thus represents a novel therapy to reduce immune surveillance in the tumor microenvironment. The present study is the first to identify that CD45 is involved in IL-10-activated signaling in myeloid lineage cells.

Gemifloxacin (GMF) is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT). In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-αand inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

The aim of this retrospective study was to evaluate the first-line treatment of bevacizumab combined with the FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen, and to compare the toxicity and efficacy in Taiwanese patients with metastatic colorectal cancer (mCRC). Fifty-two patients with mCRC receiving bevacizumab combined with FOLFIRI chemotherapy in Kaohsiung Medical University Hospital between January 2008 and December 2009 were analyzed retrospectively. The patients were initially treated with bevacizumab [5 mg/kg; a 120-minute intravenous (IV) infusion] on Day 1, followed by irinotecan (180 mg/m 2 as a 120-minute IV infusion), leucovorin (400 mg/m 2 IV infusion over 2 hours), and 5-fluorouracil (400 mg/m 2 as an IV bolus infusion followed by 2400 mg/m 2 IV infusion over a 46-hour period), repeated every 2 weeks. The characteristics of each patient, the adverse effects, and responses after chemotherapy were recorded. The objective responses for treatment of patients were evaluated, and the results showed that the overall response rate was 59.6% and the disease control rate was 82.7%. The major Grade 3/4 adverse events encountered in these patients were asthenia (5.8%), diarrhea (7.7%), nausea (7.7%), vomiting (3.8%), mucositis (1.9%), hematological toxicity (3.8%), and proteinuria (1.9%). The most common Grade 3/4 adverse events in our patients were diarrhea (0–15% in Caucasians, 4.2% in Asian, and 7.7% in the current study), nausea/vomiting (0–6%/0–7% in Caucasians and 7.7%/3.8% in the current study), neutropenia (9.5–30% in Caucasians and 3.8% in the current study), hypertension (0–26% in Caucasians and 0% in the current study), and gastrointestinal bleeding (0–4% in Caucasians and 0% in the current study). The considerable efficacy and safety profile in this retrospective study showed that bevacizumab combined with FOLFIRI regimen is consistent with the results in prospective randomized clinical trials. The combination of bevacizumab with FOLFIRI regimen for first-line treatment was effective for and well tolerated by Taiwan mCRC patients.

Recent studies indicate that a high level of nesfatin-1/Nucleobindin-2 (NUCB-2) is associated with poor outcome and promotes cell migration in breast cancer and prostate cancer. However, the role of NUCB2 is not well known in colon cancer. In this study, NUCB-2 level in colon cancer tissue was higher than that in non-tumor tissue. Suppression of NUCB-2 in a colon cancer cell line SW620 inhibited migration and invasion. The microarray analysis showed that low expression level of transcription factor ZEB1 in NUCB-2 knockdowned SW620 cells. In addition, expression level of epithelial-mesenchymal transition (EMT)-related molecules including N-cadherin, E-cadherin, β-catenin, Slug and Twist was affected by NUCB-2 suppression and ZEB1-denepdent pathway. The signaling pathway liver kinase B1(LKB1)/AMP-dependent protein kinase (AMPK)/target of rapamycin complex (TORC) 1 was involved in regulation of NUCB-2-mediated metastasis and EMT properties. Suppression of NUCB-2 inhibited tumor nodules formation in a murine colon tumor model as well. In summary, nesfatin-1/NUCB-2 enhanced migration, invasion and EMT in colon cancer cells through LKB1/AMPK/TORC1/ZEB1 pathways in vitro and in vivo.

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. DNA double-strand breaks (DSBs) are deleterious lesions that can lead to chromosomal anomalies, genomic instability and cancer. The histone H2AX plays an important role in response to DNA damage and phosphorylation of H2AX (p-H2AX) is evidence of DSBs. The aim of this study was to evaluate the clinical significance of p-H2AX expression in CRC.p-H2AX expression in CRC tissues was analyzed by immunohistochemistry and correlated with clinicopathological variables using the chi-square test. The prognostic value of p-H2AX for distant metastasis-free survival (DMFS) and overall survival (OS) was evaluated by Kaplan-Meier estimates and the individual prognostic components were analyzed with Cox regression analysis.A high p-H2AX expression in CRC tissues was associated with tumor stage and perineurial invasion. Furthermore, a high p-H2AX expression was associated with poor DMFS and OS. Cox regression analysis also revealed that p-H2AX was an independent predictor of DMFS and OS.A high p-H2AX expression in CRC tissues is associated with a more malignant cancer behavior, as well as poor patient survival. p-H2AX may, therefore, be an independent prognostic predictor for CRC, as well as a potential therapeutic target.

Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up.

Tumor micro-environment is a critical factor in the development of cancer. The aim of this study was to investigate the inflammatory cytokines secreted by tumor-associated dendritic cells (TADCs) that contribute to enhanced migration, invasion, and epithelial-to-mesenchymal transition (EMT) in colon cancer. The administration of recombinant human chemokine (C-C motif) ligand 5 (CCL5), which is largely expressed by colon cancer surrounding TADCs, mimicked the stimulation of TADC-conditioned medium on migration, invasion, and EMT in colon cancer cells. Blocking CCL5 by neutralizing antibodies or siRNA transfection diminished the promotion of cancer progression by TADCs. Tumor-infiltrating CD11c(+) DCs in human colon cancer specimens were shown to produce CCL5. The stimulation of colon cancer progression by TADC-derived CCL5 was associated with the up-regulation of non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), which subsequently increased the expression of Snail. Blocking MALAT-1 significantly decreased the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the enhancement of Snail, suggesting that the MALAT-1/Snail pathway plays a critical role in TADC-mediated cancer progression. In conclusion, the inhibition of CCL5 or CCL5-related signaling may be an attractive therapeutic target in colon cancer patients.

Treatment of intestinal bezoar causing obstruction is usually straightforward by an open approach, with either digital fragmentation or removal of the bezoar via an enterotomy. Herein, we report a case of small bowel bezoar obstruction treated successfully by laparoscopic technique. The bezoar was fragmented manually via a minilaparotomy and then pushed into the cecum with laparoscopic forceps. Laparoscopic management is an alternative to conventional surgery for intestinal bezoar that provides shorter hospital stay and less postoperative pain and may be recommended as the treatment of choice of such patients.