Yuan-Ching Chang

The Roles of Serum Leptin Concentration and Polymorphism in Leptin Receptor Gene at Codon 109 in Breast Cancer

Aims: We investigated the relationship between serum leptin concentrations and polymorphism of the leptin receptor gene and breast cancer. Methods: Serum leptin concentrations were measured by enzyme-linked immunosorbent assay in 47 women with invasive breast cancer compared with 41 age-matched controls without cancer. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the leptin receptor gene at codon 109 (LEPR-109) was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Patients with breast cancer had a higher mean serum leptin concentration than women in the control group, but the difference was not statistically significant. Among those with breast cancer, the serum leptin concentration was higher in women with high-grade cancers (p = 0.020). The LEPR-109RR genotype was more frequent in premenopausal patients with tumors larger than 2 cm (p = 0.039) and in premenopausal women who were overweight (p = 0.029). Among patients with the LEPR-109RR genotype, higher mean serum leptin concentrations were present in those with triple-negative cancers (p = 0.048). Conclusions: Our study suggests an association between serum leptin concentration and tumor progression. LEPR-109 polymorphism in premenopausal women appears to be associated with obesity and tumor progression.

Phyllodes Tumor of the Breast: The Challenge Persists

IntroductionPhyllodes tumors of the breast are uncommon, and it is difficult to predict biologic behavior based on clinicopathologic features. Despite the wealth of data on the factors to predict recurrence, little is known about the impact of treatment refinements. This study seeks to define changes in patient characteristics, histopathologic parameters, and outcome between the two periods before and after the care of patients with breast diseases was centralized to a breast specialty.MethodsThe records of 182 patients with phyllodes tumors managed surgically were reviewed. Patients treated from 1985 to 1996 (n = 81) were compared with those seen from 1997 to 2004 (n = 101).ResultsThe analysis of the two treatment periods revealed that there was a decrease in tumor size at diagnosis, from 7.7 cm during the earlier period to 4.6 cm during the recent period (P = 0.003). The patients undergoing breast-conserving surgery were significantly increased during the recent period. In contrast, pathologic features and local recurrence rates remained unchanged during the study period. Multivariate analysis revealed that positive surgical margin was the only independent predictor of recurrence, with an increased hazard of 8.0. Overall, upgrading to the next grade was observed in 16% of recurrences.ConclusionsBreast-conserving surgery with clear margins is the current treatment of choice for phyllodes tumors, but this strategy does not further reduce local recurrence effectively. Optimal management continues to be a challenge.

Blood neutrophil‐to‐lymphocyte ratio correlates with tumor size in patients with differentiated thyroid cancer

Inflammation has been implicated in the initiation and progression of thyroid cancer. Neutrophil‐to‐lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. The aim of this study was to examine the relationship between NLR and clinicopathological features in patients with differentiated thyroid cancer.

Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways.

The incidence of thyroid cancer has remarkably increased in recent years. Epidemiologic data suggest that obesity is associated with an increased incidence of several types of malignancies, including thyroid cancer. Leptin, an adipocyte-derived cytokine, has been shown to be involved in cancer development and progression. We previously demonstrated that papillary thyroid cancer expressing leptin receptor and/or leptin has a higher incidence of lymph node metastasis. In this study, we investigated the effects of leptin on cell migration in K1 and B-CPAP papillary thyroid cancer cells. Expression of leptin receptor was observed in both cell lines. Leptin enhanced the migratory activity significantly in a dose-dependent manner. We showed that leptin induced AKT and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of phosphatidylinositol 3-kinase and ERK activation using pharmacological inhibitors effectively blocked leptin-induced migration of K1 and B-CPAP cells. Taken together, this study provides new mechanistic evidence for a role of leptin in the regulation of papillary thyroid cancer progression by stimulating tumor cell migration.

Factors associated with prolonged stay after laparoscopic cholecystectomy in elderly patients

BackgroundLaparoscopic cholecystectomy in elderly patients has been linked to higher complication rates and longer lengths of stay. The purpose of this study was to identify risk factors associated with prolonged postoperative hospitalization in elderly patients undergoing laparoscopic cholecystectomy.MethodsThe records of 287 patients aged 65 years or older, who underwent successful laparoscopic cholecystectomy between January 2001 and July 2006, were retrospectively reviewed. Clinical data was abstracted from the chart and compared between patients with a shorter or longer postoperative stay.ResultsThe median postoperative hospital stay was three days (interquartile range 3–5). Forty-eight patients had complications, with an overall morbidity of 16% and mortality of 0.7%. The only independent predictor of prolonged postoperative stay was the occurrence of any major complication [odds ratio, 3.144; 95% confidence interval (CI), 1.882–5.251]. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) and underlying chronic obstructive pulmonary disease were independently associated with major complications.ConclusionsA major complication is the most important cause of prolonged hospital stay after laparoscopic cholecystectomy in the elderly. No specific comorbidity has direct impact on the duration of hospitalization, but pulmonary disease is associated with increased risk of major complications.

Leptin: The link between overweight and primary hyperparathyroidism?

Primary hyperparathyroidism is one of the most common causes of hypercalcemia. Most cases result from sporadic benign monoclonal adenomas or hyperplasia. Increased body weight is consistently present in cohorts of patients with primary hyperparathyroidism. It has been shown that fat mass is the major determinant of serum parathyroid hormone levels independent of vitamin D status. Leptin, an adipocyte-derived hormone with mitogenic activity, regulates energy homeostasis and mineral metabolism. Serum leptin levels increase in parallel to the amount of adipose stores. Interestingly, a positive association between leptin and parathyroid hormone levels is observed. Patients with primary hyperparathyroidism have higher serum leptin levels than healthy subjects. In addition, leptin administration in mice increases circulating levels of parathyroid hormone. We hypothesize that leptin involves pathogenesis of primary hyperparathyroidism and represents a link between hyperparathyroidism and increased body weight.

Expression of serine peptidase inhibitor Kunitz type 1 in differentiated thyroid cancer

SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61–68% of papillary thyroid cancer and 41–50% of follicular thyroid cancer. The overexpression diminished in anaplastic thyroid cancer. The SPINT1 expression in normal thyroid tissues and benign thyroid lesions was low. Furthermore, we noted that the SPINT1 expression was associated with extrathyroidal invasion, lymphovascular invasion, lymph node metastasis, advanced TNM stage, and a higher risk of recurrence in differentiated thyroid cancer. The results were in accordance with our analysis of The Cancer Genome Atlas data. In conclusion, an overexpression of SPINT1 appears to be associated with an invasive phenotype in differentiated thyroid cancer.

Bowen's Disease of the Nipple in a Woman with Tongue Cancer

Bowens disease, or squamous cell carcinoma in situ (SCCIS) of the skin, is a malignant neoplasm restricted to the epidermis, without evidence of dermal invasion. It usually develops in sun-exposed areas of skin, but other sites can also be affected. However, Bowens disease of the nipple is extremely rare. We present a case of Bowens disease of the nipple in a middle-aged woman who presented with a scaly lesion on the nipple for several months. She also had tongue cancer and received surgical excision following concurrent chemoradiotherapy 10 years earlier. The patient was treated with a simple mastectomy and sentinel lymph node biopsy. To the best of our knowledge, this is the first reported case in the literature of Bowens disease of the nipple in a woman with tongue cancer. Bowens disease of the nipple clinically resembles Pagets disease. Therefore, even when diagnostic imaging cannot rule out breast cancer, squamous cell carcinoma should be included in differential diagnosis of scaly lesion of the nipple.

Abstract 2948: c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in local anesthetics-induced apoptosis in human thyroid cancer cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Local anesthetics are known to induce apoptosis in clinically relevant concentrations. However, it is unknown whether the effects are also present in thyroid cancer cells and the mechanisms are not well uncharacterized. We sought to explore the effects of lidocaine and bupivacaine on thyroid cancer cells in terms of cell growth, colony formation, cell cycle, induction of apoptosis, and mitochondrial injury. At 24 hour, lidocaine had an IC50 value of 6.8 mM to 7.3 mM, whereas bupivacaine had an IC50 value of 1.3 mM to 3.1 mM. In search for a molecular mechanism, based on microarray and pathway analysis, we determined that apoptotic activity is mediated by the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK). Our data suggest that induction of apoptosis by local anesthetics has the potential to improve the regional control of thyroid cancer. Citation Format: Shih-Ping Cheng, Yuan-Ching Chang, Yi-Chiung Hsu, Shih-Yuan Huang, Meng-Chun Hu, Chin-Wen Chi, Sung-Liang Yu. c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in local anesthetics-induced apoptosis in human thyroid cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2948. doi:10.1158/1538-7445.AM2013-2948

Abstract 5752: Expression and biological significance of adiponectin receptors in papillary thyroid carcinoma

Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with pleiotropic roles in metabolism and in the development and progression of cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that levels of AdipoR1 and AdipoR2 were commonly increased in thyroid cancer compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitor trichostatin A. We determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27% of primary tumors and AdipoR2 in 47%. AdipoR1 expression correlated with AdipoR2 expression in primary tumors and in metastatic lymph nodes. Tumor AdipoR1 expression was associated with larger tumor size, whereas negative AdipoR2 expression was significantly associated with extrathyroidal invasion and multicentricity. Patients in the high AMES risk group had negative tumor expression of AdipoR1 and AdipoR2. Collectively, altered expression of adiponectin receptors in thyroid cancer supports a potential role in the pathogenesis of thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5752. doi:1538-7445.AM2012-5752