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Background: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. Methods: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. Results: Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response ( p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression ( p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group ( p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. Conclusion: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response. [ABSTRACT FROM AUTHOR]

Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment. [ABSTRACT FROM AUTHOR]

Ovarian metastasis from malignant melanoma is rare and usually appears as a solid ovarian mass. We report a case of ovarian metastasis from cutaneous malignant melanoma that proved to be a diagnostic dilemma. The ovarian metastasis exhibited a multilocular cystic appearance on magnetic resonance imaging, mimicking a mucinous ovarian tumor with massive ascites. [ABSTRACT FROM AUTHOR]

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum. Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group. Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression. This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis. [ABSTRACT FROM AUTHOR]

Angiogenesis plays an important role in tumor growth and metastasis. Thymidine phosphorylase ( TP), as well as vascular endothelial growth factor (VEGF), is known to be an angiogenic factor. The aim of this study was to clarify whether TP regulates angiogenesis and to determine the clinicopathological role of TP expression in gallbladder cancer. Thirty-seven patients with gallbladder cancer who underwent curative surgical resection were included in this study, and we evaluated results in 21 of these patients in whom TP gene expression could be measured. Intratumoral TP gene expression was evaluated using the Danenberg tumor profile method. TP gene expression was classified into two groups according to median values: high and low. Tissue TP expression was classified into two groups (positive and negative) by a pathologist. Clinicopathological variables were compared between groups with high and low TP gene expression ( TP high and TP low groups). No correlation was observed between TP gene expression (high and low groups) and any clinicopathological variables except survival rate. However, the survival rate was significantly lower in the TP high group ( P < 0.05). TP gene expression was associated with tissue TP expression evaluated by immunohistochemical staining ( P < 0.05). In addition, tumor microvessel density was significantly higher in the TP high group ( P < 0.05). Expression of the TP gene in gallbladder carcinoma is associated with angiogenesis and may be a new independent prognostic parameter. [ABSTRACT FROM AUTHOR]

Background: The objective of this article is to define the imaging characteristics of ancient schwannoma, which is a rare variant of benign schwannoma with degenerative changes, arising in the female pelvis simulating ovarian tumors. Methods: Eleven surgically proven ancient schwannomas of the female pelvis were evaluated retrospectively on the basis of CT and MR findings. Results: Typical intra-pelvic schwannoma was a neurologically asymptomatic large mass, which may situate at presacral or lateral pelvic region with the continuity to the nerve or neural foramen. Ancient schwannomas manifested as encapsulated solid masses with random or eccentric cystic areas, or as cystic masses with marginal crescent-shaped or nodular solid components. Hemorrhagic changes and calcifications were often observed on MRI and CT respectively. To detect ipsilateral normal ovary and to demonstrate centripetal displacement of the adjacent rectum or iliac vessels were helpful to diagnose the tumor as an extra-ovarian mass situated at the extraperitoneal region. Conclusions: Diagnosis of ancient schwannoma before surgical treatment is important and should be made by its characteristic clinical and imaging findings. [ABSTRACT FROM AUTHOR]

Background: Inhibiting phosphorylation of platelet-derived growth factor receptor (PDGFR) by treatment with the PDGFR kinase inhibitor imatinib and the chemotherapeutic agent paclitaxel reduces the incidence and size of human prostate cancer bone lesions in nude mice. Because tumor cells and tumor-associated endothelial cells express activated PDGFR, the primary target for imatinib has been unclear. Methods: We selected multidrug-resistant human PC-3MM2 prostate cancer cells (termed PC-3MM2-MDR cells) by culturing them in increasing concentrations of paclitaxel. PC-3MM2-MDR cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group). Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1). All statistical tests were two-sided. Results: PC-3MM2-MDR cells were resistant to paclitaxel and imatinib in vitro. Treatment of implanted mice with imatinib plus paclitaxel led to statistically significant decreases in bone tumor incidence (control = 19 mice with tumors of 19 mice total; imatinib plus paclitaxel = four of 18 mice; P<.001), median tumor weight (control = 1.3 g, interquartile range [IQR] = 1.0-1.9; imatinib plus paclitaxel = 0.1 g, 1QR = 0–0.3; P<.001), bone lysis, and the incidence of lymph node metastasis (control = 19 of 19 mice total; imatinib plus paclitaxel = three of 18 mice; P<.001). Treatment with imatinib alone had similar effects, and imatinib treatment also inhibited phosphorylation of PDGFR on tumor cells and tumor-associated endothelial cells and increased the level of apoptosis of endothelial cells, but not tumor cells. Treatment with imatinib and more so with imatinib and paclitaxel decreased mean vessel density (three CD31/PECAM-1-positive cells, 95% confidence interval [CI] = 0 to 9; and control group = 38 CD31/PECAM-1-positive cells, 95% CI = 17 to 59) (P<.001), which was followed by apoptosis of tumor cells. Conclusion: Tumor-associated endothelial cells, rather than tumor cells themselves, appear to be the target for imatinib in prostate cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Rationale: IkappaB kinase-beta is a critical regulator in the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor related to the expression and regulation of proinflammatory cytokines.Objective: To evaluate if inhibition of IkappaB kinase-beta ameliorates pneumonitis and pulmonary fibrosis.Methods: We examined whether a novel IkappaB kinase-beta inhibitor, IMD-0354, attenuates bleomycin-induced pulmonary fibrosis in mice.Measurements and Main Results: Administration of IMD-0354 significantly improved the loss of body weight and survival of mice treated with bleomycin, whereas IMD-0354 alone did not cause any morphologic change in the lung. When mice were evaluated 28 d after bleomycin administration, IMD-0354 dose-dependently reduced the collagen content and fibrotic scores as shown by histologic examination. The findings in the bronchoalveolar lavage demonstrated that the proportions of neutrophils and lymphocytes were decreased in mice treated with IMD-0354 on Day 7 and 14, respectively. IMD-0354 treatment was confirmed to inhibit the activation of NF-kappaB, but not activator protein-1, in the lungs treated with bleomycin. The production of inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta was reduced in the lungs of mice treated with IMD-0354.Conclusions: These results suggest that IMD-0354 might be useful to ameliorate the inflammation in the lungs induced by fibrotic injury and the subsequent fibrogenesis via inhibiting the expression of profibrotic cytokines related to the activation of NF-kappaB. [ABSTRACT FROM AUTHOR]