MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P?=?0.0257) and poor prognosis (P?=?0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.     

Epithelioid sarcoma mimicking a primary osseous multifocal scapula lesion

This report describes a case of bone involvement by epithelioid sarcoma, which on imaging had the appearance of a primary intraosseous lesion of the scapula. The tumor initially presented as a subcutaneous nodule which was mistakenly diagnosed as "fibrosis" following initial resection. The lesion recurred locally and after several resections presented with several ulcerated subcutaneous nodules, at which time all imaging studies were performed. The patient was treated with en bloc upper humeral interscapulothoracic resection and shoulder reconstruction. Two years after the operation the patient is alive without local recurrence or metastasis.     

Enhanced Incorporation of 1-β-D-Arabinofuranosylcytosine by Pretreatment with Etoposide

We examined the effects of timing of administration of etoposide on cytosine arab-inoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.     

Acute aortic dissection with new massive cerebral infarction - a successful repair with ligature of the right common carotid artery.

It remains unclear whether or not the infarcted brain caused by aortic dissection should be reperfused when an emergency operation is needed for aortic arch dissection. A 64-year-old woman presented with severe back pain and syncope with a sudden left hemiplegia. CT scan demonstrated an aortic dissection of the entire aorta, obstruction of the right common carotid artery by extended aortic dissection, cerebral infarction of the right middle cerebral artery territory, brain edema and pericardial effusion. Though she was unable to communicate with us, she underwent an emergent aortic arch replacement and ligature of the right common carotid artery nine hours after the onset of stroke, when massive cerebral infarction was established. She survived the operation and regained full consciousness. When brain infarction was established by extended aortic dissection in emergent aortic surgery, concomitant ligature of the responsible artery to the brain infarction may be allowed for avoiding cerebral damage leading to brain death.     

A case of small cell carcinoma of the stomach

We report a rare case of small cell carcinoma of the stomach with metastasis to the liver and invasion of the pancreas, which was associated with acute peritonitis due to perforation of the stomach. CPT-11/CDDP chemotherapy achieved a partial response. A 60-year-old man suddenly developed abdominal pain and visited the emergency room. We diagnosed acute peritonitis due to perforation of the digestive tract because CT scan showed free air in the abdominal cavity. An emergency operation was performed with an omental patch for closing the perforated hole in the stomach. Excisional biopsy was performed to the small liver nodule. Histological findings showed that the liver nodule was metastasis from small cell carcinoma. There was no finding from the thoracic CT scan, but gastroscopy revealed a giant tumor, which was diagnosed as small cell carcinoma in histology. Therefore, we diagnosed small cell carcinoma of the stomach with liver metastasis and invasion of the pancreas. After operation, one course of FP chemotherapy was performed, but the liver metastasis increased in size. Then we changed to CPT-11/CDDP chemotherapy as second-line therapy, and achieved partial remission (PR) of both the liver metastasis and gastric tumor.     

Association of neuroendocrine differentiation with neoadjuvant hormone therapy effects in prostatic cancer

Histological therapeutic effects of neoadjuvant hormone therapy (NHT) in prostatic cancer were examined, focusing on the association with neuroendocrine differentiation (NED), using 69 radical prostatectomy cases. The effects of NHT were classified into 3 grades based on the extent of tumor degeneration as observed with hematoxylin and eosin staining. NED cells in the cancer were semi-quantified into 4 grades (negative, 1+, 2+, and 3+) by immunohistochemical staining of chromogranin A (CgA). According to the therapeutic effects, the cases are divided as follows: good response in 26 patients, intermediate in 20, poor in 23. The histological therapeutic effects were significantly weaker in the CgA-positive group than the CgA-negative group (p=0.02). A close relationship between the extent of CgA expression and the histological response was also demonstrated (p=0.007). In the biopsy specimens before NHT, CgA was positive in 46% (32/69) and there was no significant difference in histological therapeutic effects between the positive and negative groups. However, the therapeutic effects were significantly weaker in 22 CgA-positive cases for both biopsy and prostatectomy specimens than in 18 CgA-negative cases for both specimens (p=0.001). In conclusion, although it seems difficult to predict the therapeutic effects of NHT using the biopsy specimens of prostatic cancer, we believe that NED is negatively associated with histological response of prostatic cancer to NHT.     

Regenerating the fibula with beta-tricalcium phosphate minimizes morbidity after fibula resection

The aim of this study was to assess the radiologic and clinical outcome when beta-tricalcium phosphate is used as a bone graft substitute to backfill the fibular defect that is created by harvesting the fibula. Fourteen patients who had fibula resections to be used as bone grafts for bone tumor resections were assessed radiographically. Callus formation bridging the beta-tricalcium phosphate was seen in 12 of 14 patients at an average of 1.4 months after surgery. In these 12 patients the beta-tricalcium phosphate mostly was absorbed and replaced by newly formed bone at an average of 9.3 months after surgery. In all children, beta-tricalcium phosphate was replaced by newly formed bone at an average of 3.2 months after surgery. Only one adult patient had complete regeneration of the fibula. Few patients had continuity between the regenerated fibula and the native fibula. In one patient in whom free vascularized fibula was harvested, regeneration of the fibula was not observed. Clinical functional outcome was not correlated with successful fibula regeneration and union with the native fibula, as determined using radiographs. The results of the study suggest that, in children, regeneration of the fibula by implanting beta-tricalcium phosphate into a bone defect can reduce morbidity of the fibula harvest sites.     

Activation of human SII cortex during exploratory finger movement and hand clenching tasks

We used electric median nerve stimuli to elucidate the functional properties of neurons in the human secondary somatosensory cortex during exploration of small objects and muscle contraction. Somatosensory evoked fields were recorded from nine healthy subjects with a 204-channel neuromagnetometer. Electrical stimuli were applied once every 3 s to the left median nerve at the wrist. The conditions during the stimulation were rest (control session), exploration of small objects (exploration session) and clenching the hand while the wrist was being electrically stimulated (clench session). The strengths of equivalent current dipoles of evoked fields from the secondary somatosensory cortex were increased during the exploration session, but those of evoked fields were decreased by the clench session.