Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments.

PURPOSE: Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines. METHODS: We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect. RESULTS: Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells. CONCLUSIONS: We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.

Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma.

Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC.

Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.

Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non-small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide-3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR-TKI-resistant NSCLC cell lines. The results showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed in several resistant cell lines, which caused the resistance to single-agent treatment with either inhibitor alone. Meanwhile, the combined therapy successfully regulated the compensatory activation of the key intracellular signals and synergistically inhibited the cell growth of those cells in vitro and in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy proved effective included (MET) mesenchymal-epithelial transition factor amplification, induction of epithelial-to-mesenchymal transition (EMT) and EGFR T790M mutation. In further analysis, the combination therapy induced the phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis cascade. Additionally, long-term treatment with the combination therapy induced the conversion from EMT to mesenchymal-to-epithelial transition in the resistant cell line harboring EMT features, restoring the sensitivity to EGFR-TKI. In conclusion, our results indicate that the combined therapy using MEK and PI3K inhibitors is a potent therapeutic strategy for NSCLC with the acquired resistance to EGFR-TKIs.

Current Multidisciplinary Approach to Fertility Preservation for Breast Cancer Patients.

Adverse effects on fertility are a significant problem for premenopausal breast cancer patients. Since April 2009, we have been referring young patients for fertility counseling provided by a multidisciplinary team. Here we evaluated the efficacy and safety of our current fertility preservation approach. We retrospectively analyzed the cases of 277 patients < 45 years old at diagnosis, which was made between 2009 and 2016. Seventy-two (26%) patients received fertility counseling. Seventeen (6%) of the 277 patients decided to preserve their fertility before starting adjuvant systemic therapy. Six (35%) patients underwent oocyte cryopreservation, and 11 (65%) married patients opted for embryo cryopreservation. There were no pregnancies among the patients undergoing oocyte cryopreservation, whereas 3 (27%) of the patients who opted for embryo cryopreservation became pregnant. Two (12%) patients stopped endocrine therapy after 2 years in an effort to become pregnant, but their breast cancers recurred. Though the problem of fertility loss for breast cancer patients is important and we should assess the infertility risk for all patients, we should also consider the prognosis. In June 2016, we launched a prospective multicenter cohort study to evaluate the efficacy and safety of fertility preservation in greater detail.

[A Case of Primary Acinic Cell Carcinoma(ACC)of the Breast].

A49 -year-old woman presented with a 3.5 cm mass in her right breast. Mammography revealed a lobular mass with poorly defined margins and no microcalcification. Ultrasonography showed a hypoechoic mass with an irregular margin. The tumor was diagnosed as breast carcinoma using a core needle biopsy. The patient underwent a modified radical mastectomy with sentinel lymph node biopsy, and received adjuvant chemotherapy. The tumor consisted of 2 types of carcinoma. The center of the tumor was solid-tubular carcinoma, and the periphery was acinic cell carcinoma(ACC). Histopathologically, the neoplastic cells of the periphery were characterized by widespread acinic cell-like differentiation with a eosinophilic granular or clear cytoplasm, resembling acinic cells of the parotid gland(t3, f[+], ly0, v0, n0, stage II B). Immunohistochemically, the specimens tested positive for salivary gland amylase, and negative for collagen type IV , ER, PgR, and HER2. We administered UFT as adjuvant chemotherapy. Eight months after surgery, local recurrence was observed. ACC of the breast is rare, and has been reported to have a good prognosis. Further investigations are needed to elucidate its true histogenesis the appropriate treatment.

[A Case of Mediastinal Dissection by Video-Assisted Thoracoscopic Surgery (VATS)in a Patient with Mediastinal Nodal Recurrence from Thyroid Carcinoma after Primary Surgery via Median Sternotomy].

A70 's male was diagnosed with advanced papillary thyroid carcinoma and underwent total thyroidectomy with left lymph node dissection(T4a, N1b, M0, stage IV A). Six years after the surgery, subclavicular and mediastinal lymph node recurrence was observed. Radioiodine therapy was not successful for those lesions. Lymph node dissection was performed via the cervical and transsternal approaches. One year after the second surgery, cervical and mediastinal lymph node recurrence was again observed. We removed the cervical lymph nodes via the cervical approach. One month after cervical dissection, we removed the mediastinal lymph nodes via video-assisted thoracoscopic surgery(VATS). The lymph nodes were relatively easily dissected by VATS under excellent surgical views. Repeat mediastinal dissection via median sternotomy could be associated with significant complications. VATS is expected to reduce the risk of reoperation and enhance surgical outcomes.

[A Case of Minimal Thyroid Carcinoma Diagnosed by a Solitary Pulmonary Metastasis].

We report a case of minimal thyroid carcinoma diagnosed by a solitary pulmonary metastasis. A 70's man visited a medical practitioner because of chest discomfort, and there was an abnormality on the chest X-ray. Chest computed tomography(CT) showed a nodule in the right middle lobe of the lung. Positron emission tomography with 18-fluorodeoxyglucose(FDG)-PET revealed increased FDG uptake in that tumor, but did not reveal any other lesion. The tumor was clinically suspected to be a carcinoid tumor, primary lung cancer, metastatic lung cancer, or a benign tumor. Right middle lobe lobectomy was performed, and the tumor was diagnosed as a metastasis from a thyroid papillary carcinoma by pathological diagnosis during surgery. After surgery, we found a tumor in the left lobe of the thyroid by CT and US. Because the patient did not desire 131I therapy, he underwent a left hemithyroidectomy and neck dissection. There was a papillary carcinoma 1.0 cm in the thyroid gland and there were 3 cervical lymph node metastases. There has been no recurrence for 11 years after surgery.

Ectopic cervical thymoma: a case report with 18F-fluorodeoxyglucose positron emission tomography findings.

Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of (18)F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images.

Combination treatment with fulvestrant and various cytotoxic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) has a synergistic effect in estrogen receptor-positive breast cancer.

Patients with estrogen receptor (ER)-positive breast cancers have a better prognosis than those with ER-negative breast cancers, but often have low sensitivity to chemotherapy and a limited survival benefit. We have previously shown a combination effect of taxanes and fulvestrant and suggested that this treatment may be useful for ER-positive breast cancer. In this study, we evaluated the effects of combinations of hormone drugs and chemotherapeutic agents. In vitro, the effects of combinations of five chemotherapeutic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) and three hormone drugs (fulvestrant, tamoxifen, and 4-hydroxytamoxifen) were examined in ER-positive breast cancer cell lines using CalcuSyn software. Changes in chemoresistant factors such as Bcl2, multidrug resistance-associated protein 1, and microtubule-associated protein tau were also examined after exposure of the cells to hormone drugs. In vivo, tumor sizes in mice were evaluated after treatment with docetaxel or doxorubicin alone, fulvestrant alone, and combinations of these agents. Combination treatment with fulvestrant and all five chemotherapeutic agents in vitro showed synergistic effects. In contrast, tamoxifen showed an antagonistic effect with all the chemotherapeutic agents. 4-Hydroxytamoxifen showed an antagonistic effect with doxorubicin and 5-fluorouracil, but a synergistic effect with taxanes and vinorelbine. Regarding chemoresistant factors, Bcl2 and microtubule-associated protein tau were downregulated by fulvestrant. In vivo, a combination of fulvestrant and docetaxel had a synergistic effect on tumor growth, but fulvestrant and doxorubicin did not show this effect. In conclusion, fulvestrant showed good compatibility with all the evaluated chemotherapeutic agents, and especially with docetaxel, in vitro and in vivo.

Clinical efficacy of capecitabine and cyclophosphamide (XC) in patients with metastatic breast cancer.

Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR) cases were observed, but partial response (PR) was achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses.

Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

BACKGROUND: Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. METHODS: In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. RESULTS: There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). CONCLUSIONS: SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells.

INTRODUCTION: Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT. METHODS: The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes. RESULTS: mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-beta-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect. CONCLUSIONS: Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.

Influences of preoperative metformin on immunological factors in early breast cancer.

PURPOSE: Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. METHOD: We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen. RESULT: There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08). CONCLUSION: Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.

Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report.

BACKGROUND: Angiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX). CASE PRESENTATION: A 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy. CONCLUSION: Although angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision.

Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.

INTRODUCTION: Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. PATIENTS AND METHODS: We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. RESULTS: Among hormone receptor-positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node-positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II. CONCLUSION: In hormone receptor-positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.

Influence of breast density on breast cancer risk: a case control study in Japanese women.

BACKGROUND: Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. METHODS: A multicenter case-control study was performed in 530 patients and 1043 controls. Breast density was classified as C1-C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. RESULTS: Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34-2.70]; C1 vs. C4 2.85 [95% CI 1.10-7.16]). This correlation was also significant in patients in the third BMI quartile (22.3-24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38-42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17-3.15]; C1 vs. C4 11.89 [95% CI 1.56-245.17]). CONCLUSION: Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

Clinicopathological relevance of UbcH10 in breast cancer.

Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer.

Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer.

BACKGROUND: UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. METHODS: We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. RESULTS: Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. CONCLUSION: The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.

Primary closure of a spontaneous esophageal rupture under hand-assisted laparoscopy: a case report.

Spontaneous rupture of the esophagus, which is also known as Boerhaave's syndrome, is a rare life-threatening condition that requires urgent surgical management. The optimal treatment involves surgical repair of the esophageal defect, which is usually accomplished via laparotomy, thoracotomy, or both, and mediastinal debridement. Here, we report a case of spontaneous rupture of the esophagus that was treated with suturing repair and drain insertion using a hand-assisted laparoscopic approach.

[Successful removal of an intrapulmonary aberrant needle under video-assisted thoracoscopic surgery; report of a case].

Intrapulmonary aberrant needles are rare in clinical practice. We report the successful removal of intrapulmonary aberrant needle. A 59-year-old man, though he was asymptomatic, was referred to our department after an abnormal shadow had been detected on a chest X-ray. Chest X-ray and chest computed tomography (CT) showed a foreign body suspected to be a metal artifact in the left upper lobe. It was diagnosed as an intrapulmonary aberrant needle and an operation under video-assisted thoracoscopic surgery was performed. Using perioperative fluoroscopy, we could confirm the location of the needle and remove it successfully. An intrapulmonary aberrant needle should be removed surgically, even if the patient is asymptomatic, due to the development of lung abscess or pyothorax and the risk containing harmful matter to health.