To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy.
We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage ...I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively.
The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively.
Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.
Age-related macular degeneration Coleman, Hanna R, MD; Chan, Chi-Chao, MD; Ferris, Frederick L, MD ...
The Lancet,
11/2008, Volume:
372, Issue:
9652
Journal Article
Peer reviewed
Open access
Summary Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are ...increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration.
Abstract Histopathology of young individuals affected by choroideremia is rarely available to allow correlation with the clinical presentation. A 30-year-old man with choroideremia died in a motor ...vehicle accident and one eye was subjected to histopathological examination. Immunoblot analysis of protein derived from white blood cells of a living brother, also affected with choroideremia, confirmed the absence of Rab escort protein-1, the normal CHM gene product. Direct sequencing of the coding region and adjacent splice sites of the CHM gene was undertaken on genomic DNA from the living brother and revealed a transition mutation, C to T, in exon 6 (R253X) which resulted in a stop codon and was predicted to truncate the protein product. Histopathological examination of the eye of the deceased brother showed relative independent degeneration of choriocapillaris, retinal pigment epithelium, and retina, similar to observations in the mouse model of choroideremia. In addition, mild T-lymphocytic infiltration was found within the choroid. The ophthalmic features and the pathology of choroideremia are discussed in light of new findings in the current case.
Radiofrequency catheter ablation (RFCA) is an effective therapeutic strategy in eliminating drug-refractory idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT VAs). It remains ...unclear what factors affect early and late VA recurrences after ablation.
The aim of our study was to elucidate the differences between early and late recurrences after acute successful RFCA of RVOT VAs in a long-term follow-up.
A total of 220 patients with acute successful RFCA of RVOT VAs were enrolled. Detailed clinical characteristics and assessments by noninvasive and invasive electrophysiology study were explored to predict the overall, early (≤1 year), and late VA (>1 year) recurrences.
During a mean follow-up of 34.15 ± 33.74 months, 45 of 220 patients (20.5%) documented recurrence of RVOT VAs after the initial RFCA. Of these patients, 26 patients (57.8%) with recurrent VAs showed similar morphology, and 19 (42.2%) were different. Patients with recurrent VAs were associated with a higher incidence of hypertension, higher systolic blood pressure, identification of foci by pace mapping alone, shorter earliest activation time, more radiofrequency pulses required, and VA originating from the anterior free wall. Multivariate analysis demonstrated that mapping strategy and shorter earliest activation time preceding VA were associated with early recurrences (hazard ratio HR 2.26; 95% confidence interval CI 1.49-3.42; P < .001; and HR 0.91; 95% CI 0.85-0.98; P = .008, respectively), whereas hypertension was associated with late recurrence (HR 3.48; 95% CI 1.34-9.07; P = .001).
RFCA is an effective strategy in the elimination of RVOT VAs. However, early and late recurrences occur commonly. Patients with early and late VA recurrences demonstrated nonuniform patterns of clinical characteristics and electrophysiological properties.
Abstract Traditionally, the paraneoplastic retinopathies have been classified into two groups: melanoma-associated retinopathy (MAR) and cancer-associated retinopathy. MAR occurs in individuals with ...metastatic cutaneous or uveal melanoma and is characterized by nyctalopia, photopsias, and variable vision loss. In most cases, the fundus is essentially normal in appearance. More recently, there have been multiple reports of a MAR-like retinopathy with associated detachments of the retinal pigment epithelium and neurosensory retina. Such a clinical presentation has been termed paraneoplastic vitelliform retinopathy. We describe an 80-year-old man with metastatic cutaneous melanoma who developed paraneoplastic vitelliform retinopathy. For the first time, histopathology from enucleation specimens provides a clinicopathologic disease correlation with focal abnormalities in the inner nuclear and outer plexiform layers.
Abstract Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies ...of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma–associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies, ultimately the role of infectious agents in ocular adnexal neoplasms is most likely as a cofactor to genetic and environmental risk factors.
Abstract Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, ...freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two white women who had xeroderma pigmentosum with neurological degeneration: Case 1 (died at age 44 years) and Case 2 (died at age 45 years). Case 1, with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun-protected and had three skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus, and exposure keratopathy. Case 1 had bilateral optic atrophy, and Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina.
To assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol.
...Clinic-based and population-based case control study.
A total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.
DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed.
AMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined.
Strong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD.
Findings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA1 was combined with either CFH risk alleles or history of smoking.
Abstract Cystinosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. ...Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues, including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron-transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature.
Ocular manifestations of trichothiodystrophy Brooks, Brian P; Thompson, Amy H; Clayton, Janine A ...
Ophthalmology (Rochester, Minn.),
12/2011, Volume:
118, Issue:
12
Journal Article
Peer reviewed
Open access
Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and multisystem abnormalities. Many TTD patients have a defect in known DNA repair ...genes. This report systematically evaluates the ocular manifestations of the largest-to-date cohort of TTD patients and xeroderma pigmentosum (XP)/TTD patients.
Case series.
Thirty-two participants, ages 1 to 30 years, referred to the National Eye Institute for examination from 2001 to 2010; 25 had TTD and 7 had XP/TTD.
Complete, age- and developmental stage-appropriate ophthalmic examination.
Visual acuity (VA), best-corrected VA, ocular motility, state of the ocular surface and corneal endothelial cell density, corneal diameter, and lens assessment.
Developmental abnormalities included microcornea (44% TTD), microphthalmia (8% TTD, 14% XP/TTD), nystagmus (40% TTD), and infantile cataracts (56% TTD, 86% XP/TTD). Corrective lenses were required by 65% of the participants, and decreased best-corrected VA was present in 28% of TTD patients and 71% of XP/TTD patients. Degenerative changes included dry eye (32% TTD, 57% XP/TTD) and ocular surface disease identified by ocular surface staining with fluorescein (32% TTD) that usually are exhibited by much older patients in the general population. The 2 oldest TTD patients exhibited clinical signs of retinal/macular degeneration. Four XP/TTD patients presented with corneal neovascularization.
These TTD and XP/TTD study participants had a wide variety of ocular findings including refractive error, infantile cataracts, microcornea, nystagmus, and dry eye/ocular surface disease. Although many of these can be ascribed to abnormal development--likely owing to abnormalities in basal transcription of critical genes--patients may also have a degenerative course.
Proprietary or commercial disclosures may be found after the references.
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