Chromosomal imbalances in laryngeal and hypopharyngeal cancers detected by comparative genomic hybridization.

BACKGROUND: The prognostic divergence of laryngeal and hypopharyngeal carcinomas is well known. Hypopharyngeal tumors are characterized by frequent metastasis formation and local recurrence, which is the source of the unfavorable prognosis of this subtype. The aim of this study was to define chromosomal alterations associated with the aggressive behavior of hypopharyngeal tumors. METHODS: Twenty-nine head and neck squamous cell carcinomas (larynx n = 14 and hypopharynx n = 15) were analyzed by comparative genomic hybridization (CGH). Fluorescence in situ hybridization (FISH) was used to validate the CGH data and to compare the amplification pattern of the most frequently altered gene (cyclin-D1, CCND1) located on 11q13. RESULTS: The average number of genetic alterations was significantly higher in the hypopharyngeal tumors (P = 0.02). A good correlation of FISH and CGH data were seen. Gains on 11q13 were present in both subtypes, whereas amplification of CCND1 was associated with the aggressive phenotype by FISH. Chromosomal alteration, which was rarely detected in hypopharyngeal tumors but was observed in more than 50% of laryngeal carcinomas, was 8q gain. CONCLUSION: Our CGH and FISH data show that head and neck squamous cell carcinomas contain complex cytogenetic alterations and further support the hypothesis that different molecular pathways are responsible for the progression of differently localized tumors of the upper aerodigestive tract.     

Serum levels of cytoskeleton remodeling proteins and their mRNA expression in tumor tissue of metastatic laryngeal and hypopharyngeal cancers

Molecular Biology Reports - Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The...     

Cytologic diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma in sputum

A prospective study of the value of sputum cytology in the diagnosis of squamous cell carcinoma of the larynx and hypopharynx is reported. Sputum cytology established the diagnosis in 63.5% of the patients with laryngeal lesions and in 77.4% of the patients with hypopharyngeal lesions. In laryngeal cancer, a positive diagnosis by sputum cytology was related to clinical T factors (according to the TNM classification): while only 29.4% of T1 lesions were positively detected by sputum cytology, 63.3% of T2 lesions, 69.7% of T3 lesions and 79.2% of T4 lesions were so detected. In hypopharyngeal cancer, there was no discernible relationship between sputum cytodiagnosis and clinical T factors. Generally, there was only a small number of cancer cells present in the sputum in these cases. Some of the squamous cancer cells were not very conspicuous and would require careful screening of the sputum specimens to be detected.     

Gender differences in depression

Depression is twice as common in women as in men, although some concern has been raised in terms of misdiagnosing depression in men. The incidence of depression in women varies during the life span. The peak incidence during childbearing years appears to be associated with cyclic hormonal changes. Women also present with reproductive -specific mood disorders: pre-menstrual dysphoric disorder (PMDD), depression in pregnancy, postpartal mood disorder (PDD) and perimenopausal depressive disorder. Gender differences were repeatedly observed in response to antidepressant medication. Premenopausal women appear to respond poorly and to show low tolerability to TCAs, but they tend to show greater responsiveness to the SSRIs. In contrast, men and postmenopausal women can respond equally to the TCAs and SSRIs. These differences are contributed to gender differences in pharmacokinetics of antidepressants and to the influence of menstrual cycle. These findings suggest the need for a gender-specific approach to the evaluation and management of depression.     

Gender differences in the diagnosis and treatment of HIV

Many cases of HIV infection in women in the United States are diagnosed very late in the course of their illness. HIV testing should be routinely recommended if a woman presents with certain gynecologic conditions or sexually transmitted diseases. Lack of awareness of HIV status leads to the majority of new sexually transmitted HIV infections. In the United States, most AIDS cases diagnosed among females in 2004 were attributable to high-risk heterosexual contact, disproportionately affecting black and Hispanic women. Depending on the racial/ethnic community being served, obstacles to access to care, including poverty, transportation issues, and cultural and language barriers, must be overcome. The full implications of gender differences in viral load and CD4 count in the treatment of women with HIV are not yet known. Clinical trial data on HIV therapies in women are limited, and most studies that have included women have not been powered to detect gender differences in virologic and immunologic success rates. Timing and choice of treatment are affected by the pharmacokinetics of antiretroviral drugs and the long-term complications of treatment, both of which may be different for men and women with HIV infection.     

Gender differences in morningness-eveningness preference

Morningness-eveningness preference (morning-, intermediate-, evening-type) or circadian typology is the individual difference that most clearly explains the variations in the rhythmic expression of biological or behavioral patterns. The aim of this study was to analyze gender difference in morningness-eveningness preference using the Horne and Ostberg questionnaire in the largest university student population selected so far (N = 2135), with an age range 18-30 yr. Morningness-eveningness questionnaire (MEQ) score distribution closely correlated to the normal curve (range 17-78, mean = 48.25; SD = 10.11), with 338 (15.84%) morning-types, 1273 (59.62%) intermediate-types, and 524 (24.54%) evening-types. The men and women differed significantly in their mean scores (p < 0.0001) and distribution per circadian typology (p < 0.00001), with the men presenting a more pronounced eveningness preference. Three factors were identified by factor analysis: time of greatest efficiency (I), sleep time/sleep phase (II), awakening time/sleep inertia (III). The MEQ items sensitive to gender differences were essentially those included in factor I and factor II. The results are discussed in relation to recent models of circadian regulation of the sleep-wake cycle.     

Gender differences in Parkinson's disease

Because estrogen has numerous effects on dopamine neurotransmission, many researchers are interested in its possible use to either slow the progression or reduce the risk of Parkinson's disease (PD). The incidence of PD is greater in men than in women. Gender differences in neurotoxicity have been observed, and basic research in experimental animals indicates that estrogen protects neurons from various forms of injury. However, the results of retrospective surveys of the neuroprotective effects of estrogen replacement in PD have been mixed, with some showing no effect on risk and others showing a reduction in risk. A mildly significant gender difference in disability and quality-of-life reporting has been noted, with women citing greater disability and reduced quality of life. Gender differences have been shown in response to treatment of PD, for example, in how levodopa is metabolized-women have greater levodopa bioavailability. In the Parkinson's Disease on Estrogen Therapy Replacement in the Menopause Years (POETRY) study, participants were found to have improved scores on the Unified Parkinson Disease Rating Scale. Based on the POETRY results, it is hypothesized that estrogen replacement therapy (ERT) may lead to improvement in PD symptoms and provide an opportunity to reduce the dosage of antiparkinsonian medication in women.     

Gender differences in the control of energy homeostasis

The world is experiencing an epidemic of obesity and its concomitant health problems. One implication is that the normally robust negative feedback system that controls energy homeostasis must be responding to different inputs than in the past. In this review we discuss the influence of gender on the efficacy of adiposity hormones as they interact with food intake control systems in the brain. Specifically, the levels of insulin and leptin in the blood are correlated with body fat, insulin being related mainly to visceral fat and leptin to subcutaneous fat. Since females carry more fat subcutaneously and males carry more fat viscerally, leptin correlates better with total body fat in females and insulin correlates better in males. High visceral fat and plasma insulin are also risk factors for the complications of obesity, including type-2 diabetes, cardiovascular problems, and certain cancers, and these are more prevalent in males. Consistent with these systemic differences, the brains of females are more sensitive to the catabolic actions of low doses of leptin whereas the brains of males are more sensitive to the catabolic action of low doses of insulin. The implications of this are discussed.     

Gender and age differences in inheritance patterns

By analyzing legacies in California from 1890 to 1984 Judge and Hrdy (1992) detected a gender-related difference: Men with children were statistically more likely to leave all of their property to a wife than were mothers to a husband. The authors argue that men were more likely than women to remarry and have additional children. Thus, in order to transfer their wealth to their mutual children, men can leave it to their wives but women can avoid risks by giving it to the children directly. This hypothesis was tested by two experiments in which subjects were asked to put themselves in the position of a person writing a will and allocate the wealth to the surviving spouse and the children. Age and sex of the heir/heiress were experimentally varied. The results support the inclusive fitness interpretation.     

Gender differences in anaerobic power tests

The purpose of this study was to determine if the differences in anaerobic power between males and females could be accounted for by differences in body composition, strength, and neuromuscular function. A total of 82 untrained men and 99 women took part in the study. Body composition, somatotype, isometric strength, neuromuscular function were measured, and four anaerobic power tests performed. The men were significantly different from the women on all strength, power, and neuromuscular measurements except reaction time and on all anthropometric and somatotype dimensions except ectomorphy. Strength and anthropometric dimensions were similarly related to anaerobic power values within each sex. Relative fat (%fat) exerted different degrees of influence on sprint and jump performances in each sex. Removing the influence of anthropometric, strength, and neuromuscular differences by analysis of covariance reduced, but did not remove, the significant differences between the sexes. Therefore, factors other than lean body mass, leg strength, and neuromuscular function may be operating in short-term, explosive power performances to account for the differences between the sexes. The task-specific nature of anaerobic power tests and the relatively large influence of anthropometric factors on power production were confirmed.     

Gender differences in psychotic bipolar mania

Objective: This study examined gender differences in the prevalence and types of psychotic symptoms in bipolar mania.Methods: Participants were drawn from consecutive admissions to the psychiatric clinic in Chemnitz, Germany, in 2005. The diagnosis of bipolar disorder, manic episode was made within 24 hours of admission, and the severity of mania was assessed using the Young Mania Rating Scale (YMRS) and the German version of the Altman Self-Rating Mania Scale. Data collected for each patient included age at the onset of bipolar illness, number of previous episodes, social functioning between episodes, and duration of hospitalization for the index episode. Based on the Task Force for Methods and Documentation in Psychiatry system, psychotic symptoms were classified as hallucinations (visual, auditory, olfactory, tactile, acousma, somatic); delusions (paranoid, reference, guilt, grandeur, religious, erotomania, hypochondriac, poverty, jealousy); and ego disorder (thought control, thought broadcasting).Results: One hundred thirty-seven women and 109 men met the criteria for an acute manic episode, of whom 93 women and 62 men had psychotic symptoms. Compared with psychotic men, psychotic women had more delusions and hallucinations, both overall and per patient, and more delusions of reference and paranoid delusions. Psychotic women had more mixed states compared with psychotic men. Psychotic women differed from both psychotic men and nonpsychotic women on a number of clinical and social variables: they had higher YMRS scores and more previous episodes of depression despite an earlier onset of illness.Conclusion: Women with bipolar mania exhibited a specific pattern of psychotic symptoms that appeared to be associated with greater severity of the acute episode, more mixed states, and a more severe course of illness.     

Gender differences in coronary heart disease

Cardiovascular disease develops 7 to 10 years later in women than in men and is still the major cause of death in women. The risk of heart disease in women is often underestimated due to the misperception that females are ‘protected’ against cardiovascular disease. The under-recognition of heart disease and differences in clinical presentation in women lead to less aggressive treatment strategies and a lower representation of women in clinical trials. Furthermore, self-awareness in women and identification of their cardiovascular risk factors needs more attention, which should result in a better prevention of cardiovascular events. In this review we summarise the major issues that are important in the diagnosis and treatment of coronary heart disease in women. (Neth Heart J 2010;18:598–603.)     

Gender differences in dementia risk factors

Background: With the aging of the population, dementia has become an important health concern in most countries. There is a growing body of literature on the importance of cardiovascular risk factors in the development of Alzheimer's disease (AD), vascular dementia, and mixed dementia (AD with cerebrovascular disease).Objective: This article reviews the role of major risk factors in dementia between both sexes.Methods: The MEDLINE, PubMed, and HealthSTAR databases were searched between 1966 and January 2007 for English-language articles on the risk factors for dementia.Results: The distribution and prevalence of major risk factors between the sexes and age groups are varied. Female sex has been associated with increased risk of the development of AD. In women aged >75 years, rates of hypertension, hyperlipidemia, and diabetes are higher than in similarly aged men. Apolipoprotein E ε 4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women compared with men. Midlife hypertension and hypercholesterolemia in both sexes predict a higher risk of developing AD in later life. Diabetes is increasing in frequency to a greater extent in women than in men, and is associated with a substantial risk for cognitive impairment. Dementia in women (probably) and in men (possibly) is influenced by obesity in the middle of life.Conclusions: It remains critical that large prospective clinical trials be designed to assess the effect of optimum management of vascular risk factors on cognitive functioning and dementia as the primary outcome, and include women and men in numbers adequate for assessment of gender effects.     

Gender differences in S-nitrosoglutathione reductase activity in the lung

S-nitrosothiols have been implicated in the etiology of various pulmonary diseases. Many of these diseases display gender preferences in presentation or altered severity that occurs with puberty, the mechanism by which is unknown. Estrogen has been shown to influence the expression and activity of endothelial nitric oxide synthase (eNOS) which is associated with increased S-nitrosothiol production. The effects of gender hormones on the expression and activity of the de-nitrosylating enzyme S-nitrosoglutathione reductase (GSNO-R) are undefined. This report evaluates the effects of gender hormones on the activity and expression of GSNO-R and its relationship to N-acetyl cysteine (NAC)-induced pulmonary hypertension (PH). GSNO-R activity was elevated in lung homogenates from female compared to male mice. Increased activity was not due to changes in GSNO-R expression, but correlated with GSNO-R S-nitrosylation: females were greater than males. The ability of GSNO-R to be activated by S-nitrosylation was confirmed by: 1) the ability of S-nitrosoglutathione (GSNO) to increase the activity of GSNO-R in murine pulmonary endothelial cells and 2) reduced activity of GSNO-R in lung homogenates from eNOS(-/-) mice. Gender differences in GSNO-R activity appear to explain the difference in the ability of NAC to induce PH: female and castrated male animals are protected from NAC-induced PH. Castration results in elevated GSNO-R activity that is similar to that seen in female animals. The data suggest that GSNO-R activity is modulated by both estrogens and androgens in conjunction with hormonal regulation of eNOS to maintain S-nitrosothiol homeostasis. Moreover, disruption of this eNOS-GSNO-R axis contributes to the development of PH.