[show abstract][hide abstract] ABSTRACT: Brachial plexus injury is a rare complication during operation and anesthesia; it can occur as a result of various mechanisms such as inappropriate positioning, over-abduction and stretching the upper limbs. Brachial plexus injury can cause the poor function of the upper limb before recovery, and sometimes serious injury is unable to completely recovered the function permanently. Here, we report a female breast cancer patient who sustained a left brachial plexus palsy after modified radical mastectomy with immediate breast reconstruction with latissimusdorsi flap (LDF). The patient had fully recovered with normal function of her left upper limb six months postoperation after conservative treatment.
World Journal of Surgical Oncology 10/2013; 11(1):276. · 1.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: We analyzed the clinicopathological features of 9 breast malignant fibrous histiocytoma (MFH) patients. Immunohistochemistry was used to make both diagnosis and differential diagnosis, and to identify prognostic factors. All tumors lacked epithelial markers but expressed mesenchymal markers, suggesting a mesenchymal origin. Of the five cases expressing Ki-67, two of three patients with axillary lymph node involvement died between 6-8 months, and two died at 17 and 26 months after diagnosis. The two remaining cases, with low Ki-67 expression, had no recurrent or metastatic disease at 145 months after diagnosis. Previous studies have shown that surgery is the primary treatment of choice, but no clear benefit from adjuvant chemotherapy was observed. We demonstrate that axillary lymph node involvement and high expression of Ki-67 are associated with poorer prognosis. A literature review indicates surgery remains the first choice for MFH, but benefits from adjuvant chemotherapy remain unclear.
[show abstract][hide abstract] ABSTRACT: The aim of the present study was to explore the correlation between estrogen receptor α (ERα) phosphorylation at serines 118 and 167 and the responsiveness of patients with primary breast cancer to tamoxifen. Tumors from 104 patients with primary breast cancer who received adjuvant tamoxifen therapy at The Affiliated Cancer Hospital of Shantou University Medical College between January 2001 to December 2007 were subjected to immunohistochemical analysis with specific antibodies against ERα phosphorylated at either serine 118 (pERα-S118) and/or serine 167 (pERα-S167). ERα phosphorylation at the two sites was correlated with either the disease-free survival or the overall survival rate of these patients using the Kaplan-Meier survival analysis. pERα-S118 and pERα-S167 were found to be expressed in the cell nucleus of 25.0% (26/104) and 26.9% (28/104) of breast cancers, respectively. The expression of pERα-S118 was positively correlated with the human epidermal growth factor receptor-2 (HER-2) status (χ(2)=6.85, P=0.01). The Kaplan-Meier analysis revealed a poorer disease-free (P=0.022) and overall survival (P=0.013) in breast cancer patients expressing pERα-S118, but not in those expressing pERα-S167. In conclusion, pERα-S118 was correlated with the HER-2 status and predicted breast cancer resistance to tamoxifen.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. METHODS: We immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors. RESULTS: Low expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFalpha or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFalpha and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients' overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis. CONCLUSIONS: Cygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients.
BMC Cancer 05/2013; 13(1):247. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: Visualization of the cell cycle in living subjects has long been a big challenge. The present study aimed to noninvasively visualize mitotic arrest of the cell cycle with an optical reporter in living subjects. PROCEDURES: An N-terminal cyclin B1-luciferase fusion construct (cyclin B-Luc) controlled by the cyclin B promoter, as a mitosis reporter, was generated. HeLa or HCT116 cells stably expressing cyclin B-Luc reporter were used to evaluate its cell cycle-dependent regulation and ubiquitination-mediated degradation. We also evaluated its feasibility to monitor the mitotic arrest caused by Taxotere both in vitro and in vivo. RESULTS: We showed that the cyclin B-Luc fusion protein was regulated in a cell cycle-dependent manner and accumulated in the mitotic phase (M phase) in cellular assays. The regulation of cyclin B-Luc reporter was mediated by proteasome ubiquitination. In the present study, in vitro imaging showed that antimitotic reagents like Taxotere upregulated the reporter through cell cycle arrest in the M phase. Noninvasive longitudinal bioluminescence imaging further demonstrated an upregulation of the reporter consistent with mitotic arrest induced in tumor xenograft models. Induction of this reporter was also observed with a kinesin spindle protein inhibitor, which causes cell cycle blockage in the M phase. CONCLUSIONS: Our results demonstrate that the cyclin B-Luc reporter can be used to image whether compounds are capable, in vivo, of causing an M phase arrest and/or altering cyclin B turnover. This reporter can also be potentially used in high-throughput screening efforts aimed at discovering novel molecules that will cause cell cycle arrest at the M phase in cultivated cell lines and animal models.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 02/2013; · 2.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: CXC chemokine receptor type 4 (CXCR4) plays a prominent role in cancer progression and metastasis. However, its association with breast cancer subtypes is still unknown. In the current study, we analyzed the expression level and the cellular location of CXCR4 in 175 cases of human breast tumors, including 75 cases of triple-negative breast cancers (TNBCs), 41 cases of luminal-subtypes and 60 cases of HER2-positive breast cancers by using immmunohistochemistry (IHC). We found that CXCR4 was expressed more frequently in the TNBCs than in other subtypes (71% for TNBC vs. 44% for HER2-positive and 37% for luminal subtype, p<0.001). In the TNBC group, CXCR4 positive patients have a significantly higher rate of visceral metastasis (liver, lung and brain). The expression level of CXCR4 is also significantly related to tumor size, advanced TNM stage, shorter overall- and disease-free survival. However, in luminal or HER2-positive breast cancer groups, CXCR4 is not correlated with such clinico-pathological characteristics and survival. Taken together, our data indicate that CXCR4 might exert its function exclusively in TNBC patients, suggesting that targeting CXCR4 might be an effective therapy for TNBC patients.
Current Molecular Medicine 01/2013; · 4.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bioluminescence reporter proteins have been widely used in the development of tools for monitoring biological events in living cells. Currently, some assays like flow cytometry analysis are available for studying DNA synthetic phase (S-phase) targeted anti-cancer drug activity in vitro; however, techniques for imaging of in vivo models remain limited. Cyclin A2 is known to promote S-phase entry in mammals. Its expression levels are low during G1-phase, but they increase at the onset of S-phase. Cyclin A2 is degraded during prometaphase by ubiquitin-dependent, proteasome-mediated proteolysis. In this study, we have developed a cyclin A2-luciferase (CYCA-Luc) fusion protein targeted for ubiquitin-proteasome dependent degradation, and have evaluated its utility in screening S-phase targeted anti-cancer drugs. Similar to endogenous cyclin A2, CYCA-Luc accumulates during S-phase and is degraded during G2/M-phase. Using Cdc20 siRNA we have demonstrated that Cdc20 can mediate CYCA-Luc degradation. Moreover, using noninvasive bioluminescent imaging, we demonstrated accumulation of CYCA-Luc in response to 10-hydroxycamptothecin (HCPT), an S-phase targeted anti-cancer drug, in human tumor cells in vivo and in vitro. Our results indicate that a CYCA-Luc fusion reporter system can be used to monitor S-phase of cell cycle, and evaluate pharmacological activity of anti-cancer drug HCPT in real time in vitro and in vivo, and is likely to provide an important tool for screening such drugs.
PLoS ONE 01/2013; 8(1):e53291. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: S-phase kinase protein 2 (Skp2), an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined.
To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models.
Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7%) patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94) of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157) of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS), and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas.
Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a potential therapeutic target.
PLoS ONE 01/2012; 7(12):e52675. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: p73, a homologue of p53, has been located at chromosome 1p36-33, a region of frequently observed loss of heterozygosity in breast cancers. The objective of the present study was to investigate the function of p73 in Japanese with breast cancers.
Sixty Japanese patients with breast cancer were assessed by polymerase chain reaction single strand confirmation polymorphism analysis and direct sequencing to detect the p73 allele. p73 mRNA levels were also determined in 40 out of 60 patients by reverse-transcriptional polymerase chain reaction.
We analyzed the entire open reading frame of the p73 gene by polymerase chain reaction single strand confirmation polymorphism and sequencing, and failed to identify any mutations of p73 in the encoding regions detected. Loss of heterozygosity of p73 was infrequent and only found in 9% of breast carcinomas. We revealed a few polymorphisms with a frequency of 13% - 29%, which had been reported previously. Down-regulation of p73 mRNA expression was observed in tumor tissues in comparison to the normal breast tissues. A significant inverse correlation was found between p73 transcripts and high histological grade, suggesting that down-regulated p73 expression could be related to poor prognosis in those patients.
Our results suggest that p73 may serve as a tumor suppressor gene and its expression plays a role in tumorigenesis in Japanese patients with breast cancer.
Chinese medical journal 08/2011; 124(15):2275-8. · 0.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mouse models with liver-specific expression of firefly luciferase were developed that enable a noninvasive and longitudinal assessment of small-interfering RNA (siRNA)-mediated gene silencing in hepatocytes of live animals via bioluminescence imaging. Using these models, a set of lipid nanoparticles (LNPs) with different compositions of cationic lipids, polyethylene glycol (PEG), and cholesterol, were tested for their abilities in delivering a luciferase siRNA to the liver via systemic administration. A dose-dependent luciferase knockdown by LNP/siRNA assemblies was measured by in vivo bioluminescence imaging, which correlated well with the results from parallel ex vivo analyses of luciferase mRNA and protein levels in the liver. RNA interference (RNAi)-mediated target silencing was further confirmed by the detection of RNAi-specific target mRNA cleavage. A single dose of LNP02L at 3 mg/kg (siRNA) caused 90% reduction of luciferase expression and the target repression lasted for at least 10 days. With identical components, LNPs containing 2% PEG are more potent than those with 5.4% PEG. Our results demonstrate that these liver-luciferase mouse models provide a powerful tool for a high-throughput evaluation of hepatic delivery platforms by noninvasive imaging and that the molar ratio of PEG lipid can affect the efficacy of LNPs in silencing liver targets via systemic administration.
[show abstract][hide abstract] ABSTRACT: beta-Galactosidase (beta-gal) (encoded by the lacZ gene) has been widely used as a transgene reporter enzyme. The ability to image lacZ expression in living transgenic animals would further extend the use of this reporter. It has been reported that 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-beta-d-galactopyranoside (DDAOG), a conjugate of beta-galactose and 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one), is not only a chromogenic lacZ substrate but that the cleavage product has far-red fluorescence properties detectable by in vivo imaging. In an attempt to noninvasively image lacZ expression in vivo, we applied fluorescence imaging to a G protein-coupled receptor (GPR56), knockout (KO) mouse model, in which the lacZ gene is introduced in the GPR56 locus. Compared to wild-type (WT) mice, GPR56KO/LacZ mice showed three- to fourfold higher fluorescence intensity in the head area 5 min after tail-vein injection of DDAOG. beta-Gal staining in sections of whole brain showed strong lacZ expression in homozygotes, but not in WT mice, consistent with lacZ activity detected by in vivo imaging. The kidneys were also visualized with fluorescence imaging both in vivo and ex vivo, consistent with beta-gal staining findings. Our results demonstrate that fluorescence imaging can be used for in vivo real-time detection of lacZ activity by fluorescence imaging in lacZ transgenic mice. Thus, this technology can potentially be used to noninvasively image changes of certain endogenous molecules and/or molecular pathways in transgenic animals.
Assay and Drug Development Technologies 09/2009; 7(4):391-9. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have applied noninvasive optical imaging technology to the in vivo hollow fiber assay, using tumor cell lines in which optical reporters are expressed in response to activation/inhibition of a specific molecular pathway. In vivo noninvasive imaging of molecular pathways in cells within hollow fibers enables a rapid and accurate evaluation of drug targets and provides useful insights to guide novel drug discovery. In this protocol we show, as an example, that a luciferase reporter, driven by the responsive element of nuclear factor NF-kappaB, was induced in cells within hollow fibers implanted in living mice, and a detailed procedure for in vivo bioluminescence imaging of hollow fibers is described. This approach can, in principle, be applied to image any molecular pathways of interest when appropriate reporter cells are generated. Hollow fiber encapsulation and implantation takes 2 d, and in vivo validation of reporter takes 1-2 weeks.
[show abstract][hide abstract] ABSTRACT: The in vivo hollow fiber assay, in which semipermeable hollow fibers filled with tumor cells, are implanted into animals, was originally developed to screen for anticancer compounds before assessment in more complex tumor models. To enhance screening and evaluation of anticancer drugs, we have applied optical imaging technology to this assay. To demonstrate that tumor cells inside hollow fibers can communicate with the host mice, we have used fluorescence imaging in vivo and CD31 immunostaining ex vivo to show that angiogenesis occurs around cell-filled hollow fibers by 2 weeks after subcutaneous implantation. Bioluminescence imaging has been used to follow the number of luciferase-expressing tumor cells within implanted hollow fibers; proliferation of those cells was found to be significantly inhibited by docetaxel or irinotecan. We also used bioluminescence imaging of hollow fibers to monitor the nuclear factor kappaB (NFkappaB) pathway in vivo; NFkappaB activation by lipopolysaccharide and tumor necrosis factor-alpha was evaluated in tumor cell lines genetically engineered to express luciferase controlled by an NFkappaB-responsive element. These results demonstrate that optical imaging of hollow fibers containing reporter tumor cells can be used for the rapid and accurate evaluation of antitumor activities of anticancer drugs and for measurement of molecular pathways.
Neoplasia (New York, N.Y.) 09/2007; 9(8):652-61. · 5.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently, the drug discovery process has greatly benefited from a wealth of novel druggable targets following the sequencing of the human genome and the parallel development of combinatorial chemistry and high-throughput screening technologies. The large number of drug candidates generated by this combined approach requires an evolution and refinement of in vivo measurement methodologies and animal models to cope with this flux of novel compounds. At the same time, drug developers are looking for translational biomarkers that can facilitate the clinical evaluation of the most promising molecules. Imaging technologies are particularly well suited to help address these various challenges. The authors focus the interest of this review on optical molecular imaging technology as well as reviewing how this technology is being integrated in various therapeutic areas, and how it has started to impact the preclinical drug discovery process. Finally, the potential clinical applications of optical molecular imaging are discussed.
Expert Opinion on Drug Discovery 01/2007; 2(1):65-85. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: BackgroundTo assess whether lymph nodes are consistently negative below a certain tumor size, we investigated the incidence and predictors
of lymph node metastasis in breast cancer patients with tumors under 2 cm in size.
MethodsA total of 238 breast cancer patients with tumors under 2 cm in size were retrospectively reviewed.
ResultsPreoperatively, 219 tumors were palpable while 19 were not. There was no lymph node metastasis in the nonpalpable tumors (n=19)
or those 5 mm or less in size (n=1) tumors, but 17% of those greater than 5 mm but less than 10 mm (n=30) and 29% of those
greater than 10 mm but 20 mm or less (n=188) tumors had nodal involvement.
ConclusionsOur sample size was too small to determine a specific tumor size that would warrant omission of axillary lymph node dissection.
However, axillary lymph node dissection may be avoided in breast cancer patients with clinically nonpalpable tumors.
Breast Cancer 03/1999; 6(2):167-170. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: BackgroundAbnormal glycosylation patterns have been recognized as a feature of carcinoma-associated mucins. The expression of the Tn
antigen in breast cancer tissue was investigated to assess its prognostic relevance.
MethodsFormalin-fixed, paraffin-embedded materials from 219 patients with breast cancer were used. Immunohistochemical staining of
the Tn antigen was retrospectively investigated and a lesion staining 10% or more was considered positive.
ResultsTn antigen expression was present in 99 (45%) of 219 lesions. There were no correlations between Tn antigen expression and
mean patient age, nodal status, estrogen receptor status, or menopausal status, but there was a slightly significant association
between Tn and tumor size. Patients negative for the Tn antigen had a significantly better survival rate than those who were
positive. Multivariate analysis also indicated that Tn expression correlated significantly with overall survival in addition
to nodal status and tumor size.
ConclusionsTn expression was a significant prognostic factor in breast cancer, but the significance was lost on multivariate analysis.
The biological implication of Tn expression in breast cancer needs further investigation.