Inhibition of prostate cancer growth and metastasis using small interference RNA specific for minichromosome complex maintenance component 7.

Minichromosome complex maintenance component 7 (MCM7) is a critical component of DNA replication licensing. Amplification and overexpression of MCM7 leads to high rate of prostate cancer metastasis. Recent studies indicate that MCM7 genome encodes a putative 'super-oncogene' cluster including MCM7 oncogene and a miRNA cluster that knocks down the expression of several critical tumor-suppressor genes. In this study, we constructed a vector that constitutively expresses small interference RNA (siRNA) specific for MCM7. Introduction of this vector into prostate cancer cell lines PC3 or Du145 decreases the expression of MCM7 by 80%. The vector inhibits DNA synthesis and generates growth arrest of these cancer cells. Severe combined immunodeficient mice were xenografted PC3 or Du145 tumors, and subsequently treated with this vector through tail vein injection with polyethylenimine. The animals had dramatically smaller tumor volume, less metastasis and better survival rate in comparison with the controls. As a result, intervention of MCM7 expression using siRNA approach may hold the promise for treating androgen refractory prostate cancer.

Efficacy of an intravenous proton pump inhibitor after endoscopic therapy with epinephrine injection for peptic ulcer bleeding in patients with uraemia: a case-control study.

BACKGROUND: Patients with peptic ulcer bleeding and uraemia are prone to re-bleeding. AIM: To compare the efficacy of an intravenous proton pump inhibitor in treating peptic ulcer bleeding in patients with uraemia and those without uraemia. METHODS: High-risk peptic ulcer bleeding patients received endoscopic therapy with epinephrine (adrenaline) injection plus intravenous omeprazole (40 mg bolus followed by 40 mg infusion every 12 h) for 3 days. Re-bleeding, volume of blood transfusion, hospital stay, need for surgery, and mortality were analysed. RESULTS: The uraemic group had similar 7-day re-bleeding rate (6/42, 14.29% vs. 6/46, 13.04%, P = 0.865) to that of non-uraemic patients, but more re-bleeding episodes beyond 7 days (4/42, 9.52% vs. 0/46, 0%, P = 0.032, OR [95% CI] = 1.105 [1.002-1.219]) and all-cause mortality (4/42 vs. 0/46 P = 0.032, OR [95% CI] = 1.105 [1.002-1.219]). The uraemic group also had more units of blood transfusion after endoscopic therapy (mean +/- s.d. 4.33 +/- 3.35 units vs. 2.15 +/- 1.65 units, P < 0.001), longer hospital stay (mean +/- s.d. 8.55 +/- 8.12 days vs. 4.11 +/- 1.60 days, P < 0.001) and complications during hospitalization (9/42 vs. 0/46, P = 0.001, OR [95% CI] = 1.273 [1.087-1.490]). CONCLUSION: Endoscopic therapy with epinephrine injection plus an intravenous proton pump inhibitor can offer protection against early re-bleeding in uraemic patients with peptic ulcer bleeding, but has a limited role beyond 7 days.

Comparison of two-phase (201)Tl SPECT with chest CT to differentiate thoracic malignancies from benign lesions.

AIM: This study was conducted to compare the performance of (201)Tl single photon emission computed tomography ((201)Tl SPECT) with chest computed tomography (CT) in differentiating thoracic malignancies from benign lesions. METHODS: One hundred and seventy patients with confirmed diagnostic thoracic lesions found in chest radiographs were prospectively examined by (201)Tl SPECT. The performance of (201)Tl SPECT in differentiating thoracic malignancies from benign lesions was evaluated in 161 patients with a measurable retention index (RI), using the region-of-interest method. Chest CT scans were retrospectively collected from 165 patients and were interpreted by two independent observers. RESULTS: The areas under the receiver operating characteristics curves were 0.85 using the RI value to differentiate thoracic malignancies from benign lesions. The sensitivity, specificity, and accuracy were 71.9%, 83.1%, and 76.4%, respectively, with a cutoff level for the RI set at 20%. Similarly, the sensitivity, specificity and accuracy of chest CT scans to differentiate malignancies from benign lesions were 78.2%, 69.7% and 74.9%, respectively. Focusing on patients with concordant results in both (201)Tl SPECT and chest CT scans, we can differentiate thoracic malignancies from benign lesions with a sensitivity of 89.1%, a specificity of 90%, and an accuracy of 89.4%. CONCLUSION: Both (201)Tl SPECT and chest CT scans are useful imaging tools in differentiating thoracic malignancies from benign lesions, with an accuracy of around 75%. By combining these two image modalities, the accuracy improves to 89.4%, which may circumvent the need for invasive procedures for certain equivocal cases, using either single image alone.

Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. METHODS: Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. RESULTS: The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. CONCLUSION: These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.

MCM7 amplification and overexpression are associated with prostate cancer progression.

The genomic DNA profiles of prostate cancers with aggressive features were compared to the profiles of matched normal DNA to identify genes that are selectively amplified in the cancer cells. One of the identified genes, MCM7, which is a component of the DNA replication licensing complex, has been studied extensively both at the DNA and protein levels in human prostate tissues. Approximately half of the prostate cancer specimens studied showed MCM7 gene amplification, and 60% of the aggressive prostate cancer specimens had increased MCM7 protein expression. Amplification or overexpression of MCM7 was significantly associated with relapse, local invasion and a worse tumor grade. Constitutive expression of MCM7 in a human prostate cancer cell line, DU145, resulted in markedly increased DNA synthesis and cell proliferation compared to vector-only controls, and an increased cell invasion in vitro. Indeed, MCM7 overexpression produced primary tumors 12 times larger than vector-only controls and resulted in a rapid demise of mice bearing those tumors. These studies implicate MCM7, and the DNA replication licensing gene family, in prostate cancer progression, growth and invasion.

Endometrial stromal sarcoma of twenty cases.

BACKGROUND: Endometrial stromal sarcoma is a rare neoplasm. We reviewed twenty cases to study the characteristics of this disease. METHODS: Twenty cases of endometrial stromal sarcoma were treated at our hospital. The clinical stage, treatment and outcome were retrospectively analyzed. RESULTS: Endometrial stromal sarcoma comprised 4.3% of corpus cancers and 46.4% of uterine sarcomas at our hospital. Seven cases were stage I, one was stage II, ten were stage III, and two were stage IV at the time of diagnosis. Histopathologically, seventeen cases were classified as low-grade sarcoma and three were high-grade sarcoma. Seven patients had recurrence and five of them had already died of disease. Among these recurrent patients, one was stage II and six were stage III. All three patients with high-grade sarcoma and four with low-grade sarcoma had recurrence. CONCLUSIONS: We think mitotic count is an important prognostic factor in low-grade endometrial stromal sarcoma and high-grade endometrial stromal sarcoma has a poor prognosis even with post-operative adjuvant treatment.

Scalene lymph node metastases with the negative pelvic nodes in invasive cervical carcinoma.

Cervical carcinoma spreads predominantly by lymphatic routes and lymph node metastases may occur even in early stages of disease. Metastases usually first appear in pelvic lymph nodes, then disseminate along the efferent lymphatic chain to the extrapelvic lymph nodes. Cases of positive lymph node metastases with negative pelvic nodes in invasive cervical carcinoma are extremely rare. We report a 50-year-old woman with bulky stage IIA cervical carcinoma who had scalene lymph node metastases in the absence of pelvic lymph node metastases after radical hysterectomy and postoperative pelvic irradiation. This rare "skipping" nodal metastasis was probably via posterior trunk lymphatic drainage of the bulky cervical carcinoma which mainly invaded the posterior vaginal cuff. Neoadjuvant or adjuvant chemotherapy is recommended to prolong survival of patients in such cases.