Evolution and management of diabetic tractional papillopathy: an optical coherence tomographic study.
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Adult↗
Biomedical subjects
R Kim
Publications and source records attributed to R Kim.
Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy.
Bcl-2 is an oncoprotein that plays a critical role in inhibiting apoptotic cell death in the mitochondria-dependent pathway in cancer chemotherapy. As a strategy for blocking Bcl-2 for enhancement of the chemotherapeutic effect, antisense Bcl-2 (AS Bcl-2; G3139, oblimersen sodium, Genasense) has shown promise, and there are several ongoing clinical studies with hematological malignancies as well as solid tumors. Although several preclinical and clinical studies have shown the therapeutic efficacy of Bcl-2 in combination with an anticancer drug as a chemosensitizer, in clinical trials the downregulation of Bcl-2 has not been observed with a high frequency in tumor cells. Nevertheless, previous studies showed nonantisense effects such as production of reactive oxygen species and immunostimulatory action through cytosine-phosphate-guanosine-motif in the antisense oligodeoxynucleotides. Further, Bcl-2 is able to inhibit Beclin 1-dependent autophagic cell death, which is a nonapoptotic cell death. The current status and future directions of AS Bcl-2 and the potential mechanisms for multiple roles that Bcl-2 has in cancer therapy are reviewed.
Clinical Trials as Topic↗
Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.
Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.
Adult↗
Extranuclear expression of hormone receptors in primary breast cancer.
BACKGROUND: Hormone receptor (HR)-positive breast cancer cells grow through estrogen receptor (ER)-signaling pathways that mediate both genomic and nongenomic actions, which cross-talk with growth factors associated with resistance to tamoxifen. The aim of this study was to explore the cross-talk between extranuclear expression of ER and progesterone receptor (PR) and growth factor signaling pathways in primary breast cancer. PATIENTS AND METHODS: The extranuclear expression of ER and PR was examined in 219 primary breast cancers by immunohistochemical staining. Specimens showing such expression were further examined for the expression of pAkt and aromatase. Staining reactions were scored on the basis of intensity and distribution in the tumors. RESULTS: Extranuclear expression of ER or PR was observed in 21 cases (9.5%), which included four cases for ER and 20 cases for PR. Among these patients, HER-2, pAkt, and aromatase-positivity were observed in 14 cases (66.6%), 13 cases (61.9%), and 14 cases (66.6%), respectively. On the basis of nuclear HR expression, 11 of these cases were categorized as ER-positive/PR-negative, while two were ER-negative/PR-positive. Of these 13 cases, increased pAkt staining was found in 11 cases (84.6%). In particular, among the 11 ER-positive/PR-negative cases, elevated pAkt and aromatase were found in 10 (90.9%; P<0.01) and nine cases (81.8%), respectively. CONCLUSIONS: PR is expressed extranuclearly more frequently than ER in primary breast cancer, and extranuclear HRs cross-talk with the Akt/HER-2-signaling pathways and activation of aromatase. These observations may explain the more beneficial effects of aromatase inhibitors than tamoxifen for ER-positive/PR-negative patients.
Adult↗
Transpupillary thermotherapy for subfoveal leaks in central serous chorioretinopathy.
AIM: To evaluate transpupillary thermotherapy (TTT) for the treatment of subfoveal focal leaks in central serous chorioretinopathy (CSC). METHODS: The patients presenting with long-standing CSC, but without the features of chronicity, were offered the options of TTT, photodynamic therapy (for subfoveal leaks), photocoagulation (for extrafoveal leaks), or observation. The patients who opted for TTT or observation were enrolled in this study. TTT was performed using a spot diameter of 0.5 mm for 1 min. Best-corrected visual acuity (BCVA), status of macular detachment, and fluorescein angiographic status were evaluated at 1, 3, and 6 months. RESULTS: This study included 39 patients (40 eyes) with CSC between 4 and 12 months, of whom 25 patients (25 eyes) opted for TTT for subfoveal leaks. Fourteen patients (15 eyes) were followed up without treatment. The groups were comparable in age, sex, and baseline BCVA. Minimum follow-up was 6 months. Within 3 months, TTT resulted in the resolution of the serous detachment in 24 (96%) eyes with a single session; one eye required a repeat treatment. Eight control eyes demonstrated persisting CSC at the last follow-up. Visual acuity improved in 23 (92%) treated and five (33%) control eyes; the difference in outcome was statistically significant (P<0.001). One case developed choroidal neovascularization, which resolved with visual recovery to 20/20 after repeat-TTT. CONCLUSION: TTT resulted in the resolution of CSC with subfoveal angiographic leaks with significant improvement in visual outcome, in comparison to the natural history of persistent CSC.
Adult↗
Macular hole secondary to X-linked retinoschisis.
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Child↗
Barrage laser photocoagulation for macula-sparing asymptomatic clinical rhegmatogenous retinal detachments.
PURPOSE: To evaluate the efficacy of barrage laser photocoagulation in containing macula-sparing asymptomatic clinical retinal detachments (RD). METHODS: Consecutive patients presenting with asymptomatic clinical RD were prospectively treated with barrage photocoagulation in 2-3 confluent rows, using frequency-doubled Nd:YAG (532 nm) laser on an indirect-ophthalmoscopic delivery system. The patients were reviewed at 0.5, 1.5, 3, and 6 months, and yearly thereafter. Best-corrected visual acuity (BCVA), and stability/progression of rhegmatous retinal detachment beyond the barrage were noted at each visit. RESULTS: Nineteen phakic eyes of 17 patients (nine female patients), aged 12-58 years (average: 26 years), underwent barrage laser treatment. Two women had bilateral RD. Most detachments were caused by atrophic holes, and involved at least a quadrant of retina. Seven (37%) extended superiorly with breaks above the horizontal raphe. Three eyes had partial demarcation lines, and five had posterior vitreous detachment at presentation. The minimum follow-up was 6 months (mean: 21 months; range: 6-108 months). Pretreatment anatomical and functional status was maintained in 18 (95%) eyes till the final visit. One superotemporal RD progressed across the laser barrier into macula 5 months after photocoagulation, and BCVA dropped to 6/18. Scleral buckling was performed successfully, with visual recovery to 6/6. CONCLUSIONS: Barrage photocoagulation may have a place in management of asymptomatic clinical detachments, as an effective and less morbid alternative to scleral buckling.
Adolescent↗
The role of apoptotic or nonapoptotic cell death in determining cellular response to anticancer treatment.
AIMS: Apoptosis, an early response cell death, is a useful marker for predicting tumour response after anticancer treatment; however, late-response cell death or nonapoptotic cell death, autophagy, can also be observed. This article reviews a rational model for predicting tumour response by assessing the influence of nonapoptotic cell death, and thereby developing a more efficient strategy for enhancing the therapeutic effect of anticancer treatment. METHOD: Literature search of clinical and experimental studies on "cell death and cancer" using established databases, including PUBMED. FINDINGS: Although induction of apoptosis may not contribute to overall tumour response, nonapoptotic cell death such as autophagy, which may be triggered by apoptosis, still occurs. Anticancer treatment-induced apoptosis is regulated by the balance of proapoptoic and antiapoptoic proteins through mitochondria, and resistance to apoptosis is mediated by Bcl-2-dependent and Akt-dependent pathways. Bcl-2 partially inhibits nonapoptotic cell death as well as apoptosis, whereas Akt inhibits both apoptotic and nonapoptotic cell death through several target proteins. CONCLUSIONS: Drug sensitivity is likely correlated with the accumulation of apoptotic and nonapoptotic cell deaths, which may influence overall tumour response in anticancer treatment. The ability to predict overall tumour response from the modulation of several important cell death-related proteins may result in a more efficient strategy for improving the therapeutic effect.
Animals↗
Regulation and interplay of apoptotic and non-apoptotic cell death.
Various death triggers including DNA damage, oxidative stress, and growth factor deprivation promote the loss of mitochondrial membrane potential, leading to the production of reactive oxidative species (ROS) or enhanced permeability of the mitochondrial membrane, otherwise known as mitochondrial membrane permeabilization, by insertion of Bax/Bak into the outer membrane where it interacts with voltage-dependent anion channel (VDAC)/adenine nucleotide transporter (ANT). MMP leads to the release of small pro-apoptotic molecules, which induce caspase-dependent and -independent apoptotic cell death. The production of ROS due to the loss of mitochondrial membrane potential enhances the permeability of lysosomal membranes, resulting in the release of lysosomal proteases, which contribute to mitochondrial membrane permeabilization and the lysosomal degradation mechanism of autophagic cell death. Although defects in apoptotic and non-apoptotic cell death pathways can be carcinogenic, these pathways are more or less preserved within cancer cells and can therefore influence cell death and mediate resistance to cancer treatment. This paper discusses recent advances in determining the molecular mechanisms behind regulation of apoptotic and non-apoptotic cell death, as well as the interplay between these two processes, which may lead to the development of new strategies by which to enhance the therapeutic effects of chemotherapeutic agents.
Animals↗
Role of the unfolded protein response in cell death.
Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER chaperones, GRP78 and Gadd153, play critical roles in cell survival or cell death as part of the UPR, which is regulated by three signaling pathways: PERK/ATF4, IRE1/XBP1 and ATF6. During the UPR, accumulated unfolded protein is either correctly refolded, or unsuccessfully refolded and degraded by the ubiquitin-proteasome pathway. When the unfolded protein exceeds a threshold, damaged cells are committed to cell death, which is mediated by ATF4 and ATF6, as well as activation of the JNK/AP-1/Gadd153-signaling pathway. Gadd153 suppresses activation of Bcl-2 and NF-kappaB. UPR-mediated cell survival or cell death is regulated by the balance of GRP78 and Gadd153 expression, which is coregulated by NF-kappaB in accordance with the magnitude of ER stress. Less susceptibility to cell death upon activation of the UPR may contribute to tumor progression and drug resistance of solid tumors.
Animals↗
Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunity.
Dendritic cells play a crucial role in initiating tumour immunity as well as in the immune response for invading foreign pathogens such as bacteria and viruses. For bacterial and viral infections, the immature dendritic cells (iDCs) residing in peripheral tissues are efficiently activated and matured by pathogen signals for performing the immune response. In contrast, for self-antigens, the naive T cells are not activated by iDCs but proceed to anergy/deletion, and the generation of regulatory T cells for immune tolerance. The induction of immune response and tolerance is regulated strictly by iDCs as the sensor for homeostasis of immune response in the host. Despite the identification of some tumour antigens, tumour immunity is not provoked successfully. Even though there are some critical obstacles to inhibit effective tumour immunity, tumour cells are able to exploit the functional roles of iDCs for tumour progression, which are induced by tumour-derived soluble factors such as vascular endothelial growth factor (VEGF) and functionally modulated in the microenvironment. The iDCs still remain as the critical target for provoking tumour immunity. In this review, the functional roles of tumour-associated iDCs and the strategy for targeting iDCs in effective tumour immunity for the cancer patient are discussed.
Autoantigens↗
Massive haemorrhagic retinal detachment after transpupillary thermotherapy for choroidal neovascularisation.
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Aged↗
Posterior scleritis causing combined central retinal artery and vein occlusion.
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Adult↗
Macular ischaemia as a marker for nephropathy in diabetic retinopathy.
PURPOSE: To determine whether diabetic macular ischaemia is associated with ischaemic heart disease (IHD), hyperlipidaemia, hypertension (HTN) and nephropathy. METHODS: Prospective case-control study from January to December 2001, involving 102 type 2 diabetic patients (aged 40-80 years), 59 with unilateral / bilateral macular ischaemia and 43 concurrent controls. Diabetic retinopathy was graded and macular ischaemia assessed by fundus examination, central fundus photography and fluorescein angiography. Systemic examination and laboratory investigations were done to evaluate systemic diseases. The associations were analysed by Chi-square test and Student's t-test. The significance of the variables as independent risk factors was tested by logistic regression analysis. RESULTS: Macular ischaemia was not associated with IHD (P=1.00); HTN (P=1.00) and hyperlipidaemia (P=0.30). Nephropathy was significantly associated with macular ischaemia (P=0.025; odds ratio [OR]: 2.62; 95% confidence interval [CI]: 1.16-5.9). The association remained significant after controlling for age, gender, duration of diabetes, severity of retinopathy, HTN, IHD and hyperlipidaemia. Further, the association with nephropathy was not affected by the presence of macular isachaemia in one or both the eyes (P=0.39). CONCLUSION: Macular ischaemia may serve as a marker for nephropathy in type 2 diabetes mellitus irrespective of the severity of retinopathy.
Adult↗
The effect of plants on the degradation and toxicity of petroleum contaminants in soil: a field assessment.
A field project located at the US Naval Base at Port Hueneme, California was designed to evaluate changes in contaminant concentrations and toxicity during phytoremediation. Vegetated plots were established in petroleum (diesel and heavy oil) contaminated soil and were evaluated over a two-year period. Plant species were chosen based on initial germination studies and included native California grasses. The toxicity of the impacted soil in vegetated and unvegetated plots was evaluated using Microtox, earthworm, and seed germination assays. The reduction of toxicity was affected more by contaminant aging than the establishment of plants. However, total petroleum hydrocarbon concentrations were lower by the end of the study in the vegetated plots when compared to the unvegetated soil. Although phytoremediation is an effective approach for cleaning-up of petroleum contaminated soil, a long-term management plan is required for significant reductions in contaminant concentrations.
Bacteria↗
Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome.
Aged individuals with Down syndrome (DS) develop senile plaques and neurofibrillary tangles consistent with Alzheimer disease (AD). Prior to or in parallel with AD pathology, compensatory growth responses may occur. Immunohistochemistry and confocal microscopy studies in the hippocampus from 15 individuals ranging in age from 5 months to 67 years compared markers of normal and abnormal tau accumulation (phosphorylated tau [AT8, MC-1], tau-1, N-terminal tau) with the extent and location of neuronal growth marker immunoreactivity (BDNF, GAP-43, MAP-2). In middle age (30-40 years), prior to entorhinal neuron loss, the earliest tau accumulation occurred in the outer molecular layer (OML), which was consistent with both pathological and compensatory fetal tau expression. These events were followed at a later age, associated with entorhinal neuron loss, by an increase in GAP-43. Hilar neurons exhibiting a sprouting morphology were also noted. Age-dependent observations in the DS brain in the current study parallel hippocampal compensatory responses described in entorhinal cortex lesion studies in rodents. Thus, compensatory growth responses may occur in DS prior to extensive AD pathology and may be one mechanism underlying observations in PET studies of hypermetabolism in the entorhinal cortex of individuals with DS.
Adolescent↗
Management of age-related macular degeneration.
With the increase in life expectancy across the world, the magnitude of blindness due to age-related macular degeneration (AMD) is expected to rise. Exudative form is the major cause of visual loss from AMD. Several treatment options are available for this form of the disease. However, all treatment strategies aim at preservation of residual vision rather than regaining the lost vision. Two well-proven strategies are laser photocoagulation and photodynamic therapy. Other viable options are submacular surgery, transpupillary thermotherapy and pharmacological modalities like angiostatic-steroids. Oral anti-oxidants and zinc appear to be beneficial in preventing disease progression in early cases. Further research is on to explore more efficient treatments and to prove the safety and efficacy of large number of emerging newer treatment options.
Age Factors↗
Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment.
Patients who require long-term steroid use are at risk for the development of osteonecrosis. However, the risk period for developing osteonecrosis of the femoral head has not yet been defined. The authors attempted to determine the onset of osteonecrosis of the femoral head following steroid treatment. Medical record data of patients with steroid-related osteonecrosis of the femoral head from four university hospitals were reviewed. Information was collected regarding the duration and dose of steroid use for patients who were diagnosed at the early stage by magnetic resonance imaging (MRI) without positive findings on plain radiographs (Association Research Circulation Osseous stage I osteonecrosis). Twenty-two patients were diagnosed at Association Research Circulation Osseous stage I. There were eight male and 14 female patients ranging in age from 17 to 60 years (mean 33). The total dose of steroid, which was used until the time of detection of osteonecrosis by MRI, ranged from 1800 to 15 505 mg prednisolone or its equivalent (mean 5928 mg). The period from the start of steroid treatment to the diagnosis by MRI ranged from 1 month to 16 months (mean 5.3 months). Twenty-one of 22 patients were diagnosed within 12 months of the initiation of steroid treatment. The duration of steroid treatment within this period ranged from 1 month to 12 months (mean 4.5 months). There may be a risk period of 12 months for developing femoral head osteonecrosis in patients receiving long-term steroid treatment. Close observation and more aggressive screening are recommended within the first year of long-term steroid treatment to prevent advanced osteonecrosis of the femoral head.
Adolescent↗