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Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.

Neuroendocrine neoplasm (NEN) is a common gastrointestinal (GI) tract tumor divided into the neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to mitosis and Ki-67 index. However, the objective discordance between interobserver may cause unsuitable diagnosis and misleading treatment. Nowadays, aberrant glycosylation of glycoconjugates inducing further populations of elongated complex oligosaccharide covalent attached to glycoconjugates anchored in the cell membrane by neo-synthesis of cancer-associated alteration of carbohydrate determinants were observed during cancer development. This study aimed to demonstrate the wax physisorption kinetics coupled with Fourier transform infrared (WPK-FTIR) imaging between NET and NEC in the rectum, colon, and stomach by utilizing two wax reagents (beeswax and paraplast) as glycan adsorbents for physical binding glycans of glycoconjugates based on dipole-induced dipole interaction. Results showed greater physisorption with beeswax than that of paraplast, suggesting highly populated elongated glycans of glycoconjugates adhering onto the tumor surfaces of NETs than that of adjacent benign mucosa in the rectum and colon. Besides, the WPK results of gastric NEN tissue sections showed a higher infrared absorbance ratio of beeswax-remnant to paraplast-remnant remains onto the tissue sections referring to a higher population of elongated glycans in gastric NET as compared with that of gastric NEC. Based on our findings, different anatomical locations could share similar phenomena with minor variance. In conclusion, WPK-FTIR imaging may have the potential to be employed as an alternative diagnostic method in GI NENs in the future.

Subarachnoid hemorrhage (SAH) is an important subcategory of stroke due to its unacceptably high mortality rate as well as the severe complications it causes, such as cerebral vasospasm, neurological deficits, and cardiopulmonary abnormality. Hepatoma-derived growth factor (HDGF) is a growth factor related to normal development and is involved in liver development and regeneration. This study explored the relationship between SAH and HDGF. Sixty rats were divided into five groups (n = 12/group): (A) control group; (B) rHDGF ab only group [normal animals treated with 50 µM recombinant HDGF antibodies (rHDGF ab)]; (C) SAH group; (D) SAH + pre-rHDGF ab group (SAH animals pre-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h before SAH); and (E) SAH + post-rHDGF ab group (SAH animals post-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h after SAH). At 48 h after SAH, serum and cerebrospinal fluid (CSF) samples were collected to measure the levels of pro-inflammatory factors by ELISA, and rat cortex tissues were used to measure protein levels by western blot analysis. Immunofluorescence staining for Iba-1, GFAP, TUNEL, and NeuN was detected proliferation of microglia and astrocyte and apoptosis of neuron cells. Neurological outcome was assessed by ambulation and placing/stepping reflex responses. Morphology assay showed that pre-treatment and post-treatment with rHDGF ab attenuated vasospasm after SAH. SAH up-regulated the levels of TNF-α, IL-1β, and IL-6 in both the CSF and serum samples, and both pre- and post-treatment with rHDGF ab inhibited the up-regulation of these pro-inflammatory factors, except for the serum IL-6 levels. Western blot analysis demonstrated that SAH up-regulated pro-BDNF and NFκB protein levels, and both pre- and post-treatment with rHDGF ab significantly reduced the up-regulation. The result from immunofluorescence staining showed that SAH induced proliferation of microglia and astrocyte and apoptosis of neuron cells. Both pre- and post-treatment with rHDGF ab significantly attenuated proliferation of microglia and astrocyte and inhibited apoptosis of neuron cells. Furthermore, treatment with rHDGF ab significantly improved neurological outcome. Blocking HDGF attenuates neuron cell apoptosis and vasospasm through inhibiting inflammation in brain tissue at early phase after SAH.

A new isopimarane-type diterpene glycoside, named hypomonticuside (1), was isolated from the BuOH-soluble fraction of the liquid fermentation of an endophytic fungus Corynespora smithii, derived from the stems of Ardisia cornudentata Mez (Myrsinaceae). The structure of 1 was elucidated by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D and 2D NMR techniques.

Astrocytoma is the most common and the most lethal primary brain tumor in adults. Grade IV glioblastoma is usually refractory to currently available surgical, chemotherapeutic, and radiotherapeutic treatments. The Specificity protein 1 (Sp1) transcription factor is known to regulate tumorigenesis in many cancers. The aim of this study was to investigate the clinicopathologic role of Sp1 protein in the carcinogenesis of astrocytoma. This study analyzed 98 astrocytoma cases treated at Kaohsiung Medical University Hospital during 2002-2012. Clinicopathologic parameters associated with Sp1 were analyzed by chi-square test, Kaplan-Meier analysis, and Cox regression analyses. In vitro proliferation, invasion, and migration were compared between non-siRNA groups and Sp1 siRNA groups. In glioblastoma cells treated with Sp1 siRNA, Western blot was also used to detect expressions of Sp1, Ki-67, VEGF, cyclin D1, E-cadherin, cleaved caspase-3 and Bax proteins. Expression of Sp1 was significantly associated with WHO grade (p = 0.005) and with overall survival time (p

SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-β target genes, playing a significant role in mediating the activities of TGF-β. In this study, we assessed the roles of TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy. Using immunohistochemistry, we examined TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2–4). A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479–35.229). Furthermore, a poor response (pathological tumor regression grades of 0–1) was an independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI 1.286–23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival (P = 0.023). Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.

Malignant papillary lesions are, in contrast to their benign counterpart, rare malignant tumors in the breast. To differentiate between benign or atypical and malignant papillary lesions can be difficult, especially in core biopsy specimens. In the present study, excisional or more extensive surgical specimens of 33 papillary carcinomas, 2 micropapillary carcinomas, and 17 atypical papillomas of the breast were reviewed and classified according to the latest WHO classification. Thirty-three intraductal papillomas and 49 invasive carcinomas, no special type (NST), were included in the study for comparison. CD133 expression in papillary carcinomas was significantly lower than that in benign and atypical papillomas (p

Background Currently, there is no standard salvage regimen after the failure of cisplatin-based chemotherapy for advanced urothelial carcinoma. The combination of epidermal growth factor receptor inhibitor with fluorouracil, leucovorin, and irinotecan was originally designed for the treatment of metastatic colorectal cancer. Until now, there have been no reports using this combination therapy in treating advanced upper tract urothelial carcinoma. To the best of our knowledge, this is the first report showing this possible treatment regimen for advanced upper tract urothelial carcinoma. Case presentation We report the case of a 90-year-old Chinese woman who was diagnosed with metastatic colorectal cancer and urothelial carcinoma of the bladder, ureter, and renal pelvis. The upper tract urothelial carcinoma was well controlled by the chemotherapy regimen for metastatic colorectal cancer. Considering her age, we used only laser ablation for the treatment of her urothelial carcinoma in combination with intravesical mitomycin C chemotherapy. Follow-up cystoscopy and ureterorenoscopy showed an unexpected regression of the upper tract urothelial tumor. Contrast-enhanced computed tomography also demonstrated the same results. Conclusions This novel regimen for the treatment of upper tract urothelial carcinoma may merit further investigation or evaluation in clinical trials. Electronic supplementary material The online version of this article (doi:10.1186/s13256-016-0879-6) contains supplementary material, which is available to authorized users.

This study is to characterize the sequential change in CD133 expression after preoperative chemoradiotherapy (CRT) in rectal cancer and its impact on postoperative prognosis. Forty-one patients with rectal cancer who had received CRT before surgery were selected retrospectively. In each case, immunohistochemical analysis was performed to compare CD133 expression in biopsy specimens taken before and after CRT. After CRT, CD133 expression was significantly increased in 14 (34%) patients, mildly increased in 25 (61%), and decreased in 2 (5%). However, no mucin-rich tumors showed high CD133 expression before or after CRT (p < 0.001). Disease-free survival and overall survival were significantly poorer in patients with significantly increased CD133 (p = 0.049 and p = 0.038, respectively). Increased CD133 after CRT is a significant prognostic factor in rectal cancer patients treated with preoperative CRT and surgical resection. CD133 might be an essential cancer stem cell marker.

Diabetes mellitus is characterized by elevated plasma glucose and increased rates of skin infections. Altered immune responses have been suggested to contribute to this prevalent complication, which involves microbial invasion. In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on β defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, which in turn contributed to the frequent occurrences of infection associated with diabetic wounding.

In patients with radically resected colorectal carcinoma, lymph node involvement is particularly important for a good prognosis and adjuvant therapy. The number of such lymph node recoveries is still controversial, with recommendations ranging from 6 to 17 nodes. The aim of this study is to determine if a specified minimum number of lymph nodes examined per surgical specimen can have any effect on the prognosis of patients who have undergone curative resection for T(2-4)N(0)M(0) colorectal carcinoma. Between September 1999 and January 2005, a total of 366 patients who underwent radical resection for T(2-4)N(0)M(0) colorectal carcinoma were retrospectively analyzed in a single institution. All specimen segments were fixed, with node identification performed by sight and palpation. We excluded 186 patients who received postoperative adjuvant chemotherapy via oral or intravenous transmission to prevent possible chemotherapeutic effects on patients' prognosis; therefore, a total of 180 patients with T(2-4)N(0)M(0) colorectal carcinoma were enrolled into this study. After the pathological examination, a mean of 12 lymph nodes (range 0-66) was harvested per tumor specimen. No postoperative relapse was found in this group, where the number of examined lymph nodes was 18 or more. Univariate analysis identified the size of the tumor, depth of invasion, grade of tumor, and number of examined lymph nodes, which were significantly correlated with postoperative relapse (all P0.05). Meanwhile, both the depth of tumor invasion and the number of harvested lymph nodes were independent predictors for postoperative relapse (P0.05). The 5-year overall survival rate of T(2-4)N(0)M(0) colorectal carcinoma patients who had 18 or more lymph nodes examined was significantly higher than those who had less than 18 nodes examined (P = 0.015). Nodal harvest in patients undergoing radical resection for colorectal carcinoma was highly significant in the current investigation. Our results suggest that harvesting and examining a minimum of 18 lymph nodes per surgical specimen might be taken into consideration for more reliable staging of lymph node-negative colorectal carcinoma.

The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas.Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with beta-catenin nuclear expression.The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia (p0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma.This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level.

Differential diagnosis of follicular adenoma (FA) and follicular carcinoma (FC) of the thyroid can be difficult in the routine practice of surgical pathology because the diagnosis of FC is strictly defined and determined by the presence of capsular and/or vascular invasion by the tumor. These features may be equivocal in the histologic sections. On the other hand, telomerase is expressed in many human cancers and is thought to contribute to their immortality. Human telomerase reverse transcriptase (hTERT) is the major determinant of human telomerase activity, and its expression is suggestive of capacity for unlimited replication. This case-control study examined the expression of hTERT using immunohistochemistry in 36 thyroid FC and 36 FA from patients who were matched by age and sex. The aim was to investigate the value of immunohistochemical staining for hTERT in the differential diagnosis of follicular neoplasms. The results revealed 23 cases of FC and 14 cases of FA that showed high expression of hTERT, with moderate to strong immunoreactivity. The remaining cases showed weak or negative staining. The difference between FA and FC was statistically significant (p < 0.05). In conclusion, immunohistochemical staining for hTERT can be considered an ancillary marker for differential diagnosis of FA and FC.

The title of the following article was incorrectly published: Cheng-Che E Lan, Ching-Shuang Wu, Shu-Mei Huang, Hsuan-Yu Kuo, I-Hui Wu, Chien-Hui Wen, Chee-Yin Chai, Ai-Hui Fang, and Gwo-Shing Chen. High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes. Mol. Med. 2011;17(7–8):771–9.