Publications by authors named "Mai Kim"

18 Publications

  • Page 1 of 1

Predictive factors for refractory stage I and II anti-resorptive agent-related osteonecrosis of the jaw.

Oral Radiol 2021 Jul 3. Epub 2021 Jul 3.

Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Objectives: We aimed to predict the possibility of patients with stage I and II anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) developing resistance to our treatment protocol by evaluating their clinical and imaging factors.

Materials And Methods: We enrolled 58 patients with ARONJ who underwent imaging modality. As objective variables, we considered the healing, stage-down, and stable stages as successful outcomes, and the stage-up stage as resistant-to-treatment. As explanatory variables, we investigated the clinical and imaging factors. Furthermore, we examined stage-down as an improvement outcome to compare with the stable and stage-up stages, which were considered as no-improvement outcomes. We conducted unpaired between-group comparisons on all explanatory variables using χ tests for independence.

Results: Among 58 patients, the treatment was successful in 53 (91.4%); however, the disease was resistant in five (8.6%). Among the clinical factors, the resistant patients had a longer duration of administration of bone-modifying agents (BMAs) (cut-off: 1251 days, p = 0.032, odds ratio = 11.2, 95% confidence interval 1.115-122.518). In addition, the target disease that was being treated bone metastasis of malignant tumor was the only significant refractory factor (p = 0.024, OR: 3.667 95% CI 1.159-11.603) CONCLUSIONS: A combination of metabolic and morphological imaging modalities may be useful for oral surgeons to evaluate the disease activity and predict course of refractory ARONJ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11282-021-00547-1DOI Listing
July 2021

Texture analysis of [F]-fluorodeoxyglucose-positron emission tomography/computed tomography for predicting the treatment response of postoperative recurrent or metastatic oral squamous cell carcinoma treated with cetuximab.

Ann Nucl Med 2021 Aug 20;35(8):871-880. Epub 2021 May 20.

Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.

Objective: To assess the value of the texture analysis of fluorine-F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG-PET/CT) in predicting the treatment response of postoperative recurrent or metastatic oral squamous cell carcinoma (POR/M-OSCC) treated with cetuximab.

Methods: A total of 14 patients undergoing F-FDG-PET/CT with POR/M-OSCC were divided into the responder and non-responder groups according to cetuximab response by Response Evaluation Criteria in Solid Tumors (RECIST). The regions of interest (ROI) were set at the POR/M-OSCC lesions with the highest uptake of F-FDG, and the volumetric and texture features were analyzed. The features with correlation coefficient of 0.6 or more were further evaluated using the logistic regression analysis to create a model.

Results: The SHAPE, SHAPE, metabolic tumor volume (MTV), and gray-level run-length matrix run-length nonuniformity (GLRLM) were significantly different between the responder (n = 6) and non-responder (n = 8) groups (p = 0.044, 0.042, 0.047, and 0.012, respectively). The model's area under the curve (AUC) was found to be 0.83, 0.83, 0.79, and 0.92, respectively. The heatmap with PET feature dendrogram showed four distinct clusters including them in patient's responder and non-responder groups.

Conclusions: Higher MTV, GLRLM, SHAPE, and SHAPE in F-FDG-PET images may have the prediction values for treatment response with POR/M-OSCC treated with cetuximab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12149-021-01623-6DOI Listing
August 2021

Resistance to Preoperative Oral Care Is Associated With Postoperative Pneumonia After Oesophageal Cancer Surgery.

Anticancer Res 2021 Mar;41(3):1507-1514

Division of Gastroenterological Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Background/aim: Postoperative pneumonia is a serious complication of major oesophageal surgery. We aimed to clarify the association between the degree of improvement in oral hygiene by perioperative oral care and postoperative pneumonia in oesophageal cancer patients.

Patients And Methods: Oesophageal cancer patients (n=129) who underwent esophagectomy received perioperative oral care. Their oral hygiene was evaluated using the Oral Assessment Guide (OAG). The relationship between perioperative OAG scores and postoperative complications was analysed.

Results: The average OAG scores before starting oral care, pre-operation, and post-operation were 11.0±1.7, 9.1±1.5, and 11.2±3.0, respectively (p<0.001). An increase in preoperative OAG scores was independently associated with postoperative pneumonia on multivariate analysis (p=0.027).

Conclusion: Preoperative oral care improves oral hygiene in patients undergoing oesophageal cancer surgery. No improvement in oral hygiene despite preoperative oral care was an independent predictor of postoperative pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.14909DOI Listing
March 2021

Predictive factors for dental inflammation with exacerbation during cancer therapy with FDG-PET/CT imaging.

Support Care Cancer 2021 Aug 7;29(8):4277-4284. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma, 371-8511, Japan.

Purpose: Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation.

Methods: We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system.

Results: Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8-19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2-41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT.

Conclusion: Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-020-05909-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236470PMC
August 2021

Screening Patients With Cancer Admitted to Hanoi Medical University Hospital for Palliative Care Needs.

JCO Glob Oncol 2020 08;6:1321-1327

Sydney Medical School, University of Sydney, New South Wales, Australia.

Purpose: To evaluate a screening tool for identifying which patients admitted to the oncology ward of a Vietnamese hospital should be referred to specialist palliative care (PC).

Methods: We performed a cross-sectional survey of consecutive patients hospitalized in the Department of Oncology and Palliative Care at Hanoi Medical University Hospital between June 2019 and September 2019. We translated a validated 11-item screening tool into Vietnamese and used a total score of ≥ 5 as a positive screen.

Results: One hundred participants were recruited. Forty-four patients (44%) screened positive. Of these, 37 (84%) had locally advanced or metastatic disease, 31 (70%) had uncontrolled symptoms, and 43 (98%) requested a PC consultation. A score ≥ 5 was significantly more common in patients with stage IV disease versus earlier stage, performance status of Eastern Cooperative Oncology Group (ECOG) 2 versus ECOG 0, and when life-limiting complications of cancer were present. Screening identified four patients overlooked by oncologists as needing referral, and 34% of patients requesting a referral had scores < 5.

Conclusion: This screening tool provided oncologists with easy-to-use criteria for referring patients for PC. At the same time, it relieved the work load for under-resourced PC physicians by screening out requests with low-level need. This tool should be part of routine assessment on admission in all oncology units in Vietnam.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/GO.20.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456321PMC
August 2020

Image screening for maxillo-mandibular actinomycosis with CT, F-FDG-PET/CT, and F-α-methyl tyrosine PET/CT.

Oral Radiol 2021 Jan 10;37(1):46-54. Epub 2020 Jan 10.

Department of Oral and Maxillofacial Surgery and Plastic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Shouwamachi, Maebashi City, Gunma, 371-8511, Japan.

Objectives: Clinical features and imaging findings of maxillo-mandibular actinomycosis are similar to those of intraosseous carcinoma. The purpose of this study is to clarify the characteristics of the imaging findings for screening of maxillo-mandibular actinomycosis using CT and PET.

Methods: Reports on maxillo-mandibular actinomycosis published between 1997 and 2016 were searched in PubMed using "actinomycosis," "maxilla," and "mandibular" as keywords. Ten cases suspected to have malignant tumors on diagnostic imaging findings were selected. In addition, three patients who visited Gunma University Hospital were also included. The 13 total cases were subjected to a pooled analysis of diagnostic screening of maxillo-mandibular actinomycosis using CT, F-FDG-PET/CT (FDG-PET/CT) and F-α-methyl tyrosine PET/CT (FAMT-PET/CT). Additionally, cases of intraosseous carcinoma were analyzed as comparative controls to investigate the difference between maxillo-mandibular actinomycosis and intraosseous carcinoma on CT imaging.

Results: CT images of the 13 cases with maxillo-mandibular actinomycosis were investigated; spotty-type bone resorption was observed in 66.7% (8/12). Moreover, FDG-PET/CT showed abnormal accumulation, but FAMT-PET/CT showed no apparent abnormal accumulation.

Conclusions: Clinical and imaging findings of maxillo-mandibular actinomycosis are similar to those of intraosseous carcinoma. Differential diagnostic screening can confirm spotty-type bone resorption in cortical bone with CT and specific accumulation in malignant tumors with FAMT-PET/CT. This screening facilitates the rapid implementation of therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11282-020-00421-6DOI Listing
January 2021

Correlation between F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) uptake and expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter 1 (LAT1) in primary prostate cancer.

EJNMMI Res 2019 May 31;9(1):50. Epub 2019 May 31.

Turku PET Centre, Turku, Finland.

Purpose: To evaluate the expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter1 (LAT1) in prostate cancer (PCa) and their impact on uptake of F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) which is approved for the detection of recurrent PCa.

Methods: Twenty-five hormone-naïve patients with histologically confirmed PCa underwent PET/CT before prostatectomy. Dynamic imaging was performed immediately after injection of 368 ± 10 MBq of F-fluciclovine and the uptake in PCa was expressed as SUV at six sequential 4-min time frames and as tracer distribution volume (V) using Logan plots over 0-24 min. The expression of ASCT2 and LAT1 was studied with immunohistochemistry (IHC) on a tissue microarray (TMA) containing three cores per carcinoma lesion. The TMA slides were scored independently by two trained readers based on visual intensity of ASCT2/LAT1 expression on a four-tiered scale. The correlations between ASCT2/LAT1 staining intensity, SUVmax/V, and Gleason grade group (GGG) were assessed using Spearman's rank correlation coefficient (ρ).

Results: Forty tumor foci (> 0.5 mm in diameter, max. 3 per patient) were available for TMA. In visual scoring, low, moderate, and high staining intensity of ASCT2 was observed in 4 (10%), 24 (60%), and 12 (30%) tumors, respectively. No tumors showed high LAT1 staining intensity while moderate intensity was found in 10 (25%), 25 (63%) showed low, and the remaining 5 (12%) were negative for staining with LAT1. Tumors with GGG > 2 showed significantly higher uptake of F-fluciclovine and higher LAT1 staining intensity (p < 0.05). The uptake of F-fluciclovine correlated significantly with LAT1 expression (ρ = 0.39, p = 0.01, for SUV at 2 min and ρ = 0.39, p = 0.01 for V). No correlation between ASCT2 expression and F-fluciclovine uptake or GGG was found.

Conclusions: Our findings suggest that LAT1 is moderately associated with the transport of F-fluciclovine in local PCa not exposed to hormonal therapy. Both high and low Gleason grade tumors express ASCT2 while LAT1 expression is less conspicuous and may be absent in some low-grade tumors. Our observations may be of importance when using F-fluciclovine imaging in the planning of focal therapies for PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13550-019-0518-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544711PMC
May 2019

F-FDG and F-FAMT PET-derived metabolic parameters predict outcome of oral squamous cell carcinoma.

Oral Radiol 2019 09 18;35(3):308-314. Epub 2019 Feb 18.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Objectives: L-3-[F]-Fluoro-α-methyl tyrosine (FAMT), an amino acid positron emission tomography (PET) tracer, complements [F]-fluorodeoxyglucose (FDG) in the diagnosis of malignancies. We compared the predictive ability of FAMT PET versus FDG PET regarding metastatic oral squamous cell carcinoma (OSCC) outcomes for distant metastasis, including lymph node metastasis, and identified the relevant metabolic parameters for each.

Methods: We enrolled 160 patients with OSCC who underwent PET/computed tomography using FDG and FAMT before treatment. Outcomes were assessed using clinicopathological characteristics such as the standardized uptake value (SUV, SUV), metabolic tumor volume (MTV), and total lesion glycolysis or total lesion retention. Univariate and multivariate Cox proportional hazards models were used to identify the independent predictors of disease-free survival (DFS) and overall survival (OS) during an average follow-up time of 1401.7 and 1646.0 days, respectively. Areas under the receiver operating characteristic curves were analyzed for the accuracy and predictive value of imaging parameters.

Results: Clinical parameters (excluding age) and PET metabolic parameters were significantly associated with OS. Multivariate analysis showed that an infiltrative growth pattern [p = 0.034, hazard ratio (HR) = 2.30], and the FDG-measured SUV (p = 0.045, HR = 2.45) were independent risk factors for DFS and that lymph node metastasis (p = 0.03, HR = 2.57) and the FAMT-measured MTV (p = 0.004, HR = 3.65) were independent risk factors for OS.

Conclusions: In patients with OSCC, FDG PET predicted DFS, whereas FAMT predicted OS. The two PET tracers, combined with clinical parameters, provide complementary, outcome-related diagnostic information in OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11282-019-00377-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685918PMC
September 2019

Activatable fluorescence detection of epidermal growth factor receptor positive mediastinal lymph nodes in murine lung cancer model.

PLoS One 2018 1;13(6):e0198224. Epub 2018 Jun 1.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.

It is important to detect mediastinal lymph node metastases in patients with lung cancer to improve outcomes, and it is possible that activatable fluorescence imaging with indocyanine green (ICG) can help visualize metastatic lymph nodes. Therefore, we investigated the feasibility of applying this method to mediastinal lymph node metastases in an epidermal growth factor receptor (EGFR)-positive squamous cell carcinoma of the lung. Tumors were formed by injecting H226 (EGFR-positive) and H520 (EGFR-negative) cell lines directly in the lung parenchyma of five mice each. When computed tomography revealed tumors exceeding 8 mm at their longest or atelectasis that occupied more than half of lateral lung fields, a panitumumab (Pan)-ICG conjugate was injected in the tail vein (50 μg/100 μL). The mice were then sacrificed 48 hours after injection and their chests were opened for fluorescent imaging acquisition. Lymph node metastases with the five highest fluorescent signal intensities per mouse were chosen for statistical analysis of the average signal ratios against the liver. Regarding the quenching capacity, the Pan-ICG conjugate had almost no fluorescence in phosphate-buffered saline, but there was an approximate 61.8-fold increase in vitro after treatment with 1% sodium dodecyl sulfate. Both the fluorescent microscopy and the flow cytometry showed specific binding between the conjugate and H226, but almost no specific binding with H520. The EGFR-positive mediastinal lymph node metastases showed significantly higher average fluorescence signal ratios than the EGFR-negative ones (n = 25 per group) 48 hours after conjugate administration (70.1% ± 4.5% vs. 13.3% ± 1.8%; p < 0.05). Thus, activatable fluorescence imaging using the Pan-ICG conjugate detected EGFR-positive mediastinal lymph node metastases with high specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198224PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983456PMC
December 2018

Control of Pecan Weevil With Microbial Biopesticides.

Environ Entomol 2017 12;46(6):1299-1304

Department of Entomology and Nematology, University of Florida/IFAS North Florida Research and Education Center, Quincy, FL 32351.

The pecan weevil, Curculio caryae (Horn) (Coleoptera: Curculionidae), is a key pest of pecans Carya illinoinensis ([Wangenh.] K. Koch) (Fagales: Juglandaceae). Control recommendations rely on broad spectrum chemical insecticides. Due to regulatory and environmental concerns, effective alternatives for C. caryae control must be sought for pecan production in conventional and organic systems. We explored the use of microbial biopesticides for control of C. caryae in Georgia pecan orchards. Three experiments were conducted. The first investigated an integrated microbial control approach in an organic system at two locations. Three microbial agents, Grandevo (based on byproducts of the bacterium Chromobacterium subtsugae Martin, Gundersen-Rindal, Blackburn & Buyer), the entomopathogenic nematode Steinernema carpocapsae (Weiser), and entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin, were applied to each treatment plot (0.6 ha) at different times during the season. A second experiment compared the effects of S. carpocapsae and B. bassiana applied as single treatments relative to application of both agents (at different times); survival of C. caryae was assessed approximately 11 mo after larvae were added to pots sunk in an organic pecan orchard. In a conventional orchard (with 1.0 ha plots), the third experiment compared Grandevo applications to a commonly used regime of chemical insecticides (carbaryl alternated with a pyrethroid). All experiments were repeated in consecutive years. The combined pest management tactic (experiment 1) reduced C. caryae infestation relative to non-treated control plots in both locations in 2014 and one of the two locations in 2015 (the other location had less than 1% infestation). In experiment 2, no differences among combined microbial treatments, single-applied microbial treatments or different numbers of application were observed, yet all microbial treatments reduced C. caryae survival relative to the control. In the third experiment, both Grandevo and standard chemical insecticide applications resulted in lower weevil infestation than the control (both years) and there was no difference between the insecticide treatments in 2014 although the chemical insecticide regime had slightly lower infestation in 2015. These results provide evidence that microbial biopesticides can substantially reduce pecan weevil infestations in organic and nonorganic systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ee/nvx144DOI Listing
December 2017

Effects of intratumoral inflammatory process on 18F-FDG uptake: pathologic and comparative study with 18F-fluoro-α-methyltyrosine PET/CT in oral squamous cell carcinoma.

J Nucl Med 2015 Jan 4;56(1):16-21. Epub 2014 Dec 4.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Unlabelled: The accurate depiction of both biologic and anatomic profiles of tumors has long been a challenge in PET imaging. An inflammation, which is innate in the carcinogenesis of oral squamous cell carcinoma (OSCC), frequently complicates the image analysis because of the limitations of (18)F-FDG and maximum standardized uptake values (SUV(max)). New PET parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as (18)F-fluoro-α-methyltyrosine ((18)F-FAMT), a malignancy-specific amino acid-based PET radiotracer, are considered more comprehensive in tumor image analysis. Here, we showed the substantial effects of the intratumoral inflammatory process on (18)F-FDG uptake and further study the possibility of MTV and TLG to predict both tumor biology (proliferation activity) and anatomy (pathologic tumor volume).

Methods: (18)F-FDG and (18)F-FAMT PET images from 25 OSCC patients were analyzed. SUV(max) on the tumor site was obtained. PET volume computerized-assisted reporting was used to generate a volume of interest to obtain MTV and TLG for (18)F-FDG and total lesion retention (TLR) for (18)F-FAMT. The whole tumor dissected from surgery was measured and sectioned for pathologic analysis of tumor inflammation grade and Ki-67 labeling index.

Results: The high SUV(max) of (18)F-FDG was related to the high inflammation grade. The SUV(max )ratio of (18)F-FDG to (18)F-FAMT was higher in inflammatory tumors (P < 0.05) whereas the corresponding value in tumors with a low inflammation grade was kept low. All (18)F-FAMT parameters were correlated with Ki-67 labeling index (P < 0.01). Pathologic tumor volume predicted from MTV of (18)F-FAMT was more accurate (R = 0.90, bias = 3.4 ± 6.42 cm(3), 95% confidence interval = 0.77-6.09 cm(3)) than that of (18)F-FDG (R = 0.77, bias = 8.1 ± 11.17 cm(3), 95% confidence interval = 3.45-12.67 cm(3)).

Conclusion: (18)F-FDG uptake was overestimated by additional uptake related to the intratumoral inflammatory process, whereas (18)F-FAMT simply accumulated in tumors according to tumor activity as evaluated by Ki-67 labeling index in OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.114.144014DOI Listing
January 2015

Diagnostic usefulness of ¹⁸F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma.

Eur J Nucl Med Mol Imaging 2013 Oct 26;40(11):1692-700. Epub 2013 Jun 26.

Department of Stomatology and Maxillofacial Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Purpose: L-[3-(18)F]-α-Methyltyrosine ((18)F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of (18)F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of (18)F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined.

Methods: The study group comprised 68 OSCC patients who underwent both (18)F-FAMT and (18)F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression.

Results: The sensitivity of primary tumour detection by (18)F-FAMT and (18)F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of (18)F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for (18)F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of (18)F-FAMT were significantly higher than those of (18)F-FDG. The uptake of (18)F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis.

Conclusion: (18)F-FAMT PET showed higher specificity for detecting malignant lesions than (18)F-FDG PET. The uptake of (18)F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-013-2477-9DOI Listing
October 2013

Clinical significance of ¹⁸F-α-methyl tyrosine PET/CT for the detection of bone marrow invasion in patients with oral squamous cell carcinoma: comparison with ¹⁸F-FDG PET/CT and MRI.

Ann Nucl Med 2013 Jun 24;27(5):423-30. Epub 2013 Feb 24.

Department of Stomatology and Maxillofacial Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

Objective: L-3-[(18)F]-fluoro-α-methyl tyrosine ((18)F-FAMT) is an amino acid tracer for positron emission tomography/computed tomography (PET/CT) which specifically transported into cancer cells by L-type amino acid transporter 1 (LAT1). LAT1 overexpression in tumors is significantly correlated with cell proliferation and angiogenesis. (18)F-FAMT PET/CT, fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET/CT and magnetic resonance imaging (MRI) were compared for their diagnostic performance in the detection of bone marrow invasion in patients with oral squamous cell carcinoma (OSCC).

Methods: Twenty-seven patients with OSCC on the upper or lower alveolar ridge underwent staging by MRI, (18)F-FDG PET/CT and (18)F-FAMT PET/CT studies before surgery. Post-surgical pathologic examination was used as the standard to determine the final diagnoses. The possibility of bone marrow invasion on MRI, (18)F-FDG PET/CT and (18)F-FAMT PET/CT were usually graded retrospectively into five-point score. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated according to the obtained scores.

Results: As the sensitivity of (18)F-FDG PET/CT was highest (100 %) among that of MRI (95 %) and (18)F-FAMT PET/CT (90 %), the specificity of (18)F-FAMT PET/CT was highest (85.7 %) among that of MRI (57 %) and (18)F-FDG PET/CT (14.3 %). The size of pathological tumor was accorded with that detected by (18)F-FAMT PET/CT and was smaller than that detected by (18)F-FDG PET/CT (P < 0.01). Significant difference was not found between (18)F-FAMT PET tumor volume and pathological tumor volume.

Conclusions: (18)F-FAMT PET/CT was useful and more specific than MRI or (18)F-FDG PET/CT in the detection of bone marrow invasion of OSCC and may contribute to minimize the extent of resection in oral surgery patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12149-013-0701-0DOI Listing
June 2013

Non-viral delivery of nuclear factor-kappaB decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis.

Gut 2007 Apr 1;56(4):524-33. Epub 2006 Sep 1.

Department of Research, Corgentech, Inc, South San Francisco, California, USA.

Background: Nuclear factor-kappaB (NF-kappaB) is a key transcriptional regulator of inflammatory bowel disease (IBD).

Aim: To investigate the therapeutic potential of a locally administered "non-viral" nuclear factor-kappaB decoy (NFkappaBD) in multiple experimental models of IBD.

Methods: A fully phosphorothioated decoy oligonucleotide with improved stability that specifically binds NF-kappaB and blocks inflammatory mediators regulated by this transcription factor without the help of viral envelope-assisted delivery was developed. The therapeutic effects of NFkappaBD were studied in the trinitrobenzene sulphonic acid, oxazolone and dextran sodium sulphate induced colitis models.

Results: Intracolonic administration of NFkappaBD results in the delivery of NFkappaBD to inflammatory cells and a reduction of NF-kappaB heterodimers. In the T helper cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice receiving NFkappaBD treatment exhibit a dose-dependent reduction in disease severity and a more rapid recovery to normal body weight, similar to a clinically relevant dose of budesonide. Clinical efficacy was corroborated by considerable reductions in colitis pathology and tissue levels of several pro-inflammatory markers, including tumour necrosis factor alpha, interleukin 6, interleukin 1beta and monocyte chemotactic protein 1. NFkappaBD also mitigates disease activity in the T helper cell 2-like oxazolone colitis and epithelial injury-related acute dextran sodium sulphate colitis models. Interestingly, restoration of tissue homeostasis is observed in NFkappaBD-treated animals with the rapid re-emergence of functional goblet cells and a return to normal patterns of cell proliferation in the mucosal epithelium and smooth muscle cell layers.

Conclusions: These data support the potential use of "naked" NFkappaBD as a cross-functional therapeutic in IBD, and show for the first time that it can facilitate the restoration of colon homeostasis and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gut.2006.096487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856846PMC
April 2007

Blockade of experimental atopic dermatitis via topical NF-kappaB decoy oligonucleotide.

J Invest Dermatol 2006 Aug 20;126(8):1792-803. Epub 2006 Apr 20.

Department of Research, Corgentech. Inc., South San Francisco, California, USA.

Atopic dermatitis (AD) is a common chronic skin inflammatory disease. Long-term use of topical corticosteroids in skin inflammation poses risks of systemic and local side effects. The NF-kappaB transcription factor family plays a central role in the progression and maintenance of AD. This study explores the possibility of using topical NF-kappaB Decoy as a novel therapeutic alternative for targeting Th1/Th2-driven skin inflammation in experimental AD. A high-affinity, topical NF-kappaB Decoy developed for human efficacy demonstrates: (i) efficient NF-kappaB Decoy penetration in pig skin, (ii) NF-kappaB Decoy nuclear localization in keratinocytes and key immune cells, and (iii) potent "steroid-like" efficacy in a chronic dust-mite antigen skin inflammation treatment model. NF-kappaB Decoy exerts its anti-inflammatory action through the effective inhibition of essential regulators of inflammation and by induction of apoptosis of key immune cells. Unlike betamethasone valerate (BMV), long-term NF-kappaB Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappaB Decoy, in contrast to BMV, restores compromised stratum corneum integrity and barrier function. Steroid withdrawal causes rapid rebound of inflammation, while the NF-kappaB Decoy therapeutic benefit was maintained for weeks. Thus, topical NF-kappaB Decoy provides a novel mechanism of reducing chronic skin inflammation with improved skin homeostasis and minimal side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/sj.jid.5700307DOI Listing
August 2006

Identification of genes promoting angiogenesis in mouse lung by transcriptional profiling.

Am J Respir Cell Mol Biol 2003 Aug 14;29(2):172-9. Epub 2003 Feb 14.

Department of Physiology, Faculty of Medicine Sirraj Hospital, Mahidol University, Bangkok, Thailand.

A better understanding of the regulation of factors that promote angiogenesis may ultimately enable improved therapeutic control of this important process. In our previous studies, obstruction of the left pulmonary artery in the mouse consistently induced the formation of a new vasculature, which developed from the visceral pleura and entered the upper left lung directly within 5-6 days after ligation. No new vessels developed to the lower left lung, despite the initial ischemic stimulus being identical to that in the upper lung. Using this unique model of angiogenesis, we have determined the temporal pattern of differential gene expression from two independent regions of the same lung: one where angiogenesis is induced, and the other where angiogenesis does not occur. Microarray analysis and quantitative real-time RT-PCR were used to compare the signals from these two lung regions in the first 3 d following ischemia. The findings reveal the important roles of ELR+ CXC chemokines as proangiogenic signals. Genes involved in tissue remodeling, inflammation, and injury were also upregulated in the proangiogenic upper lung. Results also confirm that lung ischemia, rather than hypoxia, is the essential trigger for angiogenesis. These altered profiles of expression in the early stage of lung ischemia show potential roles and interactions of the most important genes involved in promoting new blood vessel formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1165/rcmb.2002-0276OCDOI Listing
August 2003

Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray.

Cancer Res 2002 Sep;62(18):5196-203

Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA 21205-2179, USA.

Electrophiles formed during metabolic activation of chemical carcinogens and reactive oxygen species generated from endogenous and exogenous sources play a significant role in carcinogenesis. Cancer chemoprevention by induction of phase 2 proteins to counteract the insults of these reactive intermediates has gained considerable attention. Nuclear factor E2 p45-related factor 2 (Nrf2), a bZIP transcription factor, plays a central role in the regulation (basal and or inducible expression) of phase 2 genes by binding to the "antioxidant response element" in their promoters. Identification of novel Nrf2-regulated genes is likely to provide insight into cellular defense systems against the toxicities of electrophiles and oxidants and may define effective targets for achieving cancer chemoprevention. Sulforaphane is a promising chemopreventive agent that exerts its effect by strong induction of phase 2 enzymes via activation of Nrf2. In the present study, a transcriptional profile of small intestine of wild-type (nrf2 +/+) and knock out (nrf2 -/-) mice treated with vehicle or sulforaphane (9 micromol/day for 1 week, p.o.) was generated using the Murine Genome U74Av2 oligonucleotide array (representing approximately 6000 well-characterized genes and nearly 6000 expressed sequence tags). Comparative analysis of gene expression changes between different treatment groups of wild-type and nrf2-deficient mice facilitated identification of numerous genes regulated by Nrf2 including previously reported Nrf2-regulated genes such as NAD(P)H:quinone reductase (NQO1), glutathione S-transferase (GST), gamma-glutamylcysteine synthetase (GCS), UDP-glucuronosyltransferases (UGT),epoxide hydrolase, as well as a number of new genes. Also identified were genes encoding for cellular NADPH regenerating enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme), various xenobiotic metabolizing enzymes, antioxidants (glutathione peroxidase, glutathione reductase, ferritin, and haptaglobin), and biosynthetic enzymes of the glutathione and glucuronidation conjugation pathways. The data were validated by Northern blot analysis and enzyme assays of selected genes. This investigation expands the horizon of Nrf2-regulated genes, highlights the cross-talk between various metabolic pathways, and divulges the pivotal role played by Nrf2 in regulating cellular defenses against carcinogens and other toxins.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2002

Acrolein causes transcriptional induction of phase II genes by activation of Nrf2 in human lung type II epithelial (A549) cells.

Toxicol Lett 2002 Jun;132(1):27-36

Department of Environmental Health Sciences, Division of Toxicological Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205-2179, USA.

Acrolein, an alpha,beta-unsaturated aldehyde, is by far the strongest electrophile present in cigarette smoke which is involved in several lung pathophysiological conditions. Acrolein depletes glutathione and creates thiol imbalance. Acrolein due to thiol imbalance as well as covalent modification of cysteine is known to inhibit the activity of redox sensitive transcription factors such as NF-kappaB and AP-1. Exposure of human type II lung epithelial (A549) cells to non-lethal dose of acrolein (150 fmol/cell for 1 h) depletes 80% of intracellular glutathione and increases the transcription of gamma-glutamylcysteine synthetase (gamma-GCS) at 6-12 h post-treatment, which helps in replenishing the glutathione to normal level. Acrolein treatment activates transcription of phase II genes in general, as indicated by an increase in mRNA for NAD (P) H:quinone oxidoreductase (NQO1). Western blot analysis revealed the increased level of the transcription factor, Nrf2 in the nuclear extract from acrolein treated cells. Electrophoretic mobility shift assay shows increased binding of nuclear proteins to human antioxidant response element (ARE) consensus sequence after treatment with acrolein. The involvement of Nrf2 in ARE mediated transcriptional activation in response to acrolein exposure has been confirmed by human NQO1-ARE reporter assay. The ability of acrolein to transcriptionaly activate genes responsible for phase II enzymes may form the basis of resistance against cell death and can have implications in cigarette smoke related lung carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0378-4274(02)00055-3DOI Listing
June 2002
-->