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Background: Pulmonary carcinoid tumors are rare and usually occur sporadically. Infrequently, they arise in association with multiple endocrine neoplasia type 1 (MEN1). Familial pulmonary carcinoid tumors not associated with MEN1 have not been described., Methods: Two sets of first-degree relatives diagnosed with primary pulmonary carcinoid tumors with no clinical features of MEN1 were identified in a pair of siblings and in a mother and daughter. Mutations in the MEN1 gene were sought using polymerase chain reaction analysis on paraffin embedded tissue from two members of one of the families., Results: Histopathologic and immunohistochemical studies confirmed the diagnoses of carcinoid tumors. None of these patients and no family members had features of MEN1. DNA analysis did not detect germline mutations in the MEN1 gene., Conclusions: The occurrence of familial pulmonary carcinoid tumors in the absence of MEN1 suggests a novel, rare germline mutation specific to the development of pulmonary carcinoids., (Copyright 2001 American Cancer Society.)

Lung cancer (LC) and chronic obstructive pulmonary lung diseases (COPDs; including emphysema and chronic bronchitis) share a common etiology. Despite the known associations of alpha1-antitrypsin deficiency (alpha1AD) with COPD and COPD with LC, few studies examined the association of alpha1AD alleles and LC. We hypothesize that heterozygous individuals who carry a deficient allele of the alpha1AD gene Pi (protease inhibitor locus) are at an increased risk of developing LC. The Pi locus is highly polymorphic with >70 variants reported. There are at least 10 alleles associated with deficiency in alpha1-antitrypsin. Using an exact binomial test, we compared the alpha1AD carrier rate in 260 newly diagnosed Mayo Clinic LC patients to the reported carrier rate in Caucasians in the United States (7%). alpha1AD carrier status, determined by isoelectric focusing assay, was examined with respect to the history of cigarette smoking, COPD, and histological types. Thirty-two of the 260 patients (12.3%; 95% confidence interval, 8.6-16.9%) carried an alpha1AD allele, which was significantly higher than expected (P = 0.002). Twenty-four of the 32 carriers had allele S, 6 had allele Z, and 2 had allele I. Patients who never smoked cigarettes were three times more likely to carry a deficient allele (20.6%; P = 0.008), although smokers had a higher carrier rate (11.1%; P = 0.025) when compared with the 7% rate. Patients with squamous cell or bronchoalveolar carcinoma had a significantly higher carrier rate than expected (15.9% and 23.8%, P < or = 0.01, respectively). Our preliminary findings suggest that individuals who carry an alpha1AD allele may have an increased risk for developing LC, specifically squamous cell or bronchoalveolar carcinoma.

The etiology of non-syndromic cleft lip with or without cleft palate (CL +/- P) is unclear, although both familial and environmental factors are implicated. Because CL +/- P occurs at approximately the time of brain lateralization and is most often unilateral, developmental asymmetry effects have been postulated in CL +/- P etiology. Handedness is frequently used as an indicator of brain lateralization; therefore, several studies have examined the relationship between cleft laterality and handedness. However, these studies have had conflicting results. The present study investigated handedness in a Chinese sample of 211 non-syndromic CL +/- P surgical probands (ascertained in Shanghai for family studies of CL +/- P), 221 population-based but unmatched controls, and 272 first-degree relatives of the probands. Handedness was assessed by means of laterality quotients (LQ) calculated from questionnaire data. Mean LQ's were compared, as were various arbitrary definitions of handedness based on the LQ, for cases versus controls, males versus females, right-sided versus left-sided clefts, and cleft lip alone versus cleft lip plus cleft palate. CL +/- P cases had a significantly higher proportion of non-right-handedness (NRH) than controls, regardless of the definition of NRH (P values < or = .001). There were no statistically significant differences for any of the other comparisons. Familiarity of NRH was tested by comparing first-degree relatives of cases to controls; first-degree relatives were found to have a significantly higher proportion of NRH than controls, supporting familial effects in NRH. These results support the concept of a common etiology and/or developmental pathway for CL +/- P and handedness.

Epidemiological studies have demonstrated that diets high in vegetables and fruit are associated with a decreased risk of cancer and, possibly cardiovascular disease. Certain constituents of vegetables and fruit inhibit the in vitro activity of platelet-derived growth factor (PDGF), a potent mitogen implicated in both cancer and cardiovascular disease. Few studies have measured PDGF in relationship to diet in vivo. Specifically, there are no data regarding the changes in PDGF levels of mitogenic activity after a dietary intervention. In this study, 19 young, healthy individuals consumed four (9-day) experimental diets in random order: (a) control diet alone; (b) control diet plus carotenoid-rich vegetables; (c) control diet plus cruciferous vegetables; and (d) control diet plus soy foods. Compared to the control diet, there was a significant elevation in PDGF-AB serum levels when the individuals were consuming the soy diet (P = 0.016). Increased PDGF-AB levels were also noted for the carotenoid diet. There was no change from baseline levels when individuals were consuming the cruciferous diet. Overall, mitogenic activity did not change on any of the experimental diets. This study suggests that high soy and carotenoid diets increase serum levels of PDGF-AB. This may represent an additional mechanism by which diet influences individual risk of cancer; further investigation into the role of diet and growth factors is warranted.

Objective: Workers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms. Methods: This study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes' polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected. Results: There was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels. Conclusion: Therefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk. This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype.Methods: A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were non-smokers diagnosed with LC, and controls were composed of never-smoking individuals undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype.Results: The study included 457 cases (42%) and 631 controls (58%), with a predominance of women (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS.Conclusions: No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk. [ABSTRACT FROM AUTHOR]

Carcinoid tumours are rare neuroendocrine neoplasms that mostly occur in younger adults with low tendencies to metastasise. Based on their histological characteristics, they are divided into typical and atypical subtypes. The most common presenting symptoms are due to central airway obstruction. The first step in the diagnostic assessment should be a computed tomography (CT) scan, as it provides information both for local tumour extent and lymph node involvement. Bronchoscopy is the main tool for histological confirmation, evaluation of bronchial wall invasion and removal of endobronchial manifestation with subsequent resolution of atelectasis. Endobronchial ultrasound may be necessary to rule out lymph node metastasis. Somatostatin receptor scintigraphy in combination with CT can rule out further metastatic disease. Surgical resection using parenchyma-sparing techniques remains the gold standard for treatment. For selected patients, endobronchial therapy could be an alternative for minimal invasiveness. Long-term follow-up is suggested due to the high likelihood of recurrence. Here, we describe our clinical experience in a 35-year-old male patient who originally presented with haemoptysis and a central polypoid tumour in the left main bronchus revealed by a CT scan. The histological characteristics were indicative of a typical carcinoid. The patient was treated using an endobronchial approach only. No complications and no recurrences have been observed in a follow-up of 2 years. [ABSTRACT FROM AUTHOR]

Opinion Statement: Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable survival outcome when compared with other subtypes of lung cancers. Treatment of bronchial carcinoids is not simple owing to intricacy of symptom presentation and heterogeneity of disease biology. Successful treatment of patients requires a multimodality approach. Resection is curative in the majority of patients with localized tumors and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced disease. To date, very few randomized clinical trials have been done, partly owing to the relative rarity of this malignancy. Somatostatin analogs (SSAs) are reasonable first-line choice for patients with tumors expressing somatostatin receptors. Everolimus is an appropriate first-line choice for somatostatin receptor negative tumors and for any patients with progressive disease. PRRT can also be considered for progressive tumors expressing somatostatin receptors. Based on retrospective series, cytotoxic chemotherapy can be selected in patients with progressive tumors, primarily when cytoreduction is needed. Herein, we will discuss evidence supporting the role of adjuvant and systemic treatment therapies for those with bronchial carcinoid tumors by focusing on various studies. [ABSTRACT FROM AUTHOR]

α1-antitrypsin (AAT), a circulating glycoprotein that rises during acute phase responses and healthy pregnancies, exhibits immunomodulatory properties in several T-cell-dependent immune pathologies. However, AAT does not directly interfere with T-cell responses; instead, it facilitates polarization of macrophages and dendritic cells towards M2-like and tolerogenic cells, respectively. AAT also allows NK cell responses against tumor cells, while attenuating DC-dependent induction of autoimmune NK cell activities. Since AAT-treated macrophages bear resemblance to cancer-promoting tumor-associated macrophages (TAMs), it became imperative to examine the possible induction of tumor permissive conditions by AAT. Here, AAT treatment is examined for its effect on tumor development, metastatic spread, and tumor immunology. Systemic AAT treatment of mice inoculated with B16-F10 melanoma cells resulted in significant inhibition of tumor growth and metastatic spread. Using NK cell-resistant RMA cells, we show that AAT interferes with tumor development in a CD8+ T-cell-dependent manner. Unexpectedly, upon analysis of tumor cellular composition, we identified functional tumor-infiltrating CD8+ T-cells alongside M1-like TAMs in AAT-treated mice. Based on the ability of AAT to undergo chemical modifications, we emulated conditions of elevated reactive nitrogen and oxygen species. Indeed, macrophages were stimulated by treatment with nitrosylated AAT, and IFNγ transcripts were significantly elevated in tumors extracted soon after ischemia-reperfusion challenge. These context-specific changes may explain the differential effects of AAT on immune responses towards tumor cells versus benign antigenic targets. These data suggest that systemically elevated levels of AAT may accommodate its physiological function in inflammatory resolution, without compromising tumor-targeting immune responses. [ABSTRACT FROM AUTHOR]

Background: Pulmonary neuroendocrine tumors (NET) form a heterogeneous group of rare diseases. In these tumors, paraneoplastic syndromes have been described to drive the course of the disease, among them acromegaly induced by paraneoplastic secretion of growth hormone-releasing hormone (GHRH). Case presentation: We report the case of a 43 years old patient initially diagnosed with acromegaly accompanied by weight gain and acral enlargement. Subsequently, further diagnostic work-up identified a solitary pulmonary neuroendocrine tumor (NET). Laboratory tests revealed markedly increased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) without GHRH elevation in the absence of pituitary pathologies confirming the paraneoplastic origin of clinical presentation with acromegaly. Curative surgery was performed leading to normalization of the elevated hormone levels and improvement of the clinical symptoms. Immunohistochemically, a typical carcinoid (TC) was seen with low proliferation index and abundant IGF-1 expression. Conclusions: The association of acromegaly and pulmonary NET has only rarely been reported. We present an individual case of paraneoplastic GH- and IGF-1 secretion in a patient with pulmonary NET. Based on their rarity, the knowledge of paraneoplastic syndromes occurring in patients with pulmonary NET such as acromegaly due to paraneoplastic GH- and IGF-1 secretion is mandatory to adequately diagnose and treat these patients. [ABSTRACT FROM AUTHOR]

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One would assume that the anti-inflammatory activity of α1-anti-trypsin ( AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin ( IL)-8, ADAM metallopeptidase domain 17 ( ADAM17) and danger-associated molecular pattern ( DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity - 'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury. [ABSTRACT FROM AUTHOR]

Alpha-1 antitrypsin (AAT) gene is highly polymorphic, with a large number of rare variants whose phenotypic consequences often remain inconclusive. Studies addressing functional characteristics of AAT variants are of significant biomedical importance since deficiency and dysfunctionality of AAT are associated with liver and lung diseases. We report the results of the functional analysis of two naturally occurring AAT variants, G320R and V321F, previously identified in patients with lung disease. Neither of variants has been fully functionally characterized. In order to perform their functional analysis both variants were expressed in prokaryotic and eukaryotic systems and their intracellular localization, activity, stability, and polymerization were determined. The results of this study demonstrated that variants G320R and V321F have neither impaired activity against porcine pancreatic elastase nor propensity to form polymers. However, both variants had altered electrophoretic mobility and reduced thermostability when compared to M variant of the protein, indicating a slightly impaired secondary or tertiary structure. [ABSTRACT FROM AUTHOR]

Background The association between alpha-1 antitrypsin (AAT) deficiency and colorectal cancer (CRC) is currently controversial. The present study compares AAT serum concentrations and gene frequencies between a group of CRC patients and a control group of healthy unrelated people (HUP). Methods 267 CRC subjects (63% males, 72 ± 10 years old) were enlisted from a Hospital Clinic setting in Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 ± 7.5 years old) from the same geographical region. Outcome measures were AAT serum concentrations measured by nephelometry, and AAT phenotyping characterization by isoelectric focusing. Results Significantly higher serum concentrations were found among CRC (208 ± 60) than in HUP individuals (144 ± 20.5) (p = 0.0001). No differences were found in the phenotypic distribution of the Pi*S and Pi*Z allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC (21%) than in HUP subjects (15%). Conclusions The only statistically significant finding in this study was the markedly higher AAT serum concentrations found in CRC subjects compared with HUP controls, irrespective of whether their Pi* phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although there was a trend towards the more deficient Pi* phenotype the more advanced the tumor, the results were inconclusive due to the small sample size. Consequently, more powerful studies are needed to reach firmer conclusions on this matter. [ABSTRACT FROM AUTHOR]

Alpha1-antitrypsin deficiency, one of the three most common potentially lethal genetic disorders among whites, an autosomal recessive genetic disease, leads to early-onset panacinar emphysema, increased lung cancer risk, chronic liver disease and skin disorders. It has recently been studied the causal relationship of alpha1- antitrypsin deficiency (mainly the Z allele) to inflammatory bowel disease, but also to the increased incidence of extraintestinal manifestation, the most frequent being the cutaneous, articular and hepatic ones, as well as its relation to fibromyalgia. [ABSTRACT FROM AUTHOR]

Background: We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers. Methods: 445 cases (35% of which were never smokers oversampled by design) between the ages of 20-84 were identified through four major tertiary care hospitals in metropolitan Toronto between 1997 and 2002 and were frequency matched on sex and ethnicity with 425 population controls and 523 hospital controls. Unconditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between exposures and lung cancer risk. Results: Any previous exposure to occupational exposures (OR total population 1.6, 95% CI 1.4-2.1, OR never smokers 2.1, 95% CI 1.3-3.3), a previous diagnosis of emphysema in the total population (OR 4.8, 95% CI 2.0-11.1) or a first degree family member with a previous cancer diagnosis before age 50 among never smokers (OR 1.8, 95% CI 1.0-3.2) were associated with increased lung cancer risk. Conclusions: Occupational exposures and family history of cancer with young onset were important risk factors among never smokers. [ABSTRACT FROM AUTHOR]

Exposure to tobacco smoke is an established risk factor for lung cancer, although a possible role for genetic susceptibility in the development of lung cancer has been inferred from familial clustering of the disease and segregation analysis. Findings of familial aggregation and statistical evidence for a major susceptibility gene have led to the search for high penetrant, rare, single genes and low penetrant, high frequency susceptibility genes for lung cancer. The relatively small number of linkage studies conducted to date, have identified potential lung cancer susceptibility loci on chromosomes 6q, 12p, and 19q. A variety of studies have examined single nucleotide polymorphisms of several low penetrant, high frequency genes encoding for enzymes involved in the metabolism of carcinogens and DNA damage repair, as likely candidate susceptibility genes. These studies have produced somewhat conflicting findings and, when significant, only modest associations have been reported. Relatively few studies have looked for potential gene-environment interactions, explored associations between two or more genetic polymorphisms or evaluated interactions between genetic polymorphisms and endogenous risk factors. Few large scale genome wide association studies conducted recently have provided evidence that common variation on chromosome 15q25.1, 5p15.33 and 6p21.33 influences lung cancer risk and cancer types with strong environmental risk factors. It is hoped that newer research strategies, selecting candidate genes within pathways and genotype at multiple markers within a gene, employing new technologies, may allow complete coverage of the variation within candidate genes in multiple pathways and to unravel the genetic susceptibility to lung cancer. This knowledge could, in turn, be used to identify persons at risk, to individualize treatments such as chemoprevention, to personalize harms of smoking and to motivate cessation. [ABSTRACT FROM AUTHOR]

Previous studies report structural brain differences in individuals with nonsyndromic orofacial clefts (NSOFC) compared with healthy controls. These changes involve non-uniform shifts in tissue volume within the cerebral cortex and cerebellum, suggesting that the shape of the brain may be altered in cleft-affected individuals. To test this hypothesis, a landmark-based morphometric approach was utilized to quantify and compare brain shape in a sample of 31 adult males with cleft lip with or without cleft palate (CL/P), 14 adult males with cleft palate only (CPO) and 41 matched healthy controls. Fifteen midline and surface landmarks were collected from MRI brain scans and the resulting 3D coordinates were subjected to statistical shape analysis. First, a geometric morphometric analysis was performed in three steps: Procrustes superimposition of raw landmark coordinates, omnibus testing for group difference in shape, followed by canonical variates analysis (CVA) of shape coordinates. Secondly, Euclidean distance matrix analysis (EDMA) was carried out on scaled inter-landmark distances to identify localized shape differences throughout the brain. The geometric morphometric analysis revealed significant differences in brain shape among all three groups ( P << 0.001). From CVA, the major brain shape changes associated with clefting included selective enlargement of the anterior cerebrum coupled with a relative reduction in posterior and/or inferior cerebral portions, changes in the medio-lateral position of the cerebral poles, posterior displacement of the corpus callosum, and reorientation of the cerebellum. EDMA revealed largely similar brain shape changes. Thus, compared with controls, major brain shape differences were present in adult males with CL/P and CPO. These results both confirm and expand previous findings from traditional volumetric studies of the brain in clefting and provide further evidence that the neuroanatomical phenotype in individuals with NSOFC is a primary manifestation of the defect and not a secondarily acquired characteristic. [ABSTRACT FROM AUTHOR]

Objective: Left-handedness reportedly has been more common in persons with neurological afflictions (e.g.,stroke) and malformations (e.g.,c left lip with or without cleft palate) that demonstrate marked unilateral involvement. Coronal synostosis is also more frequently unilateral,affecting the right side more commonly than the left. We sought to compare left-handedness in patients with unilateral coronal synostosis versus healthy controls. Subjects: All patients aged 3 years or older with nonsyndromic unilateral coronal synostosis and healthy controls recruited by pediatricians blinded to the study. Main Outcome Measures: Prospective data obtained for all participants included age,gender, and handedness. In patients with unilateral coronal synostosis,the side of synostosis and age at surgery were documented. Lefthandedness in the study and control groups was compared using chi-square analysis. Left-handedness also was analyzed in the study group according to side of fusion. Results: Eighty-six patients with nonsyndromic unilateral coronal synostosis comprised the study group; there were 96 controls. The mean ages of the study (8.8 years) and control groups (9.8 years) were not statistically different (p >05). There were more girls in the study group (67%) than in the control group (56%),but this difference was not statistically significant (p >05). Lefthandedness was documented in 30.2% of the study group and 11.4% of the control group (p >005). Left-handedness was twice as common in patients with left versus right unilateral coronal synostosis (44.4% versus 20.4%; p >05). Conclusions: Left-handedness is nearly three times more common in patients with unilateral coronal synostosis than in controls and four times more likely in patients with left-sided fusion. [ABSTRACT FROM AUTHOR]

In this article, the authors focus on the needs and opportunities for integrated research on chronic obstructive pulmonary disease (COPD) and/or lung cancer. They reveal the workshop conducted by National Heart, Lung, and Blood Institute (NHLBI) and National Cancer Institute (NCI) that investigates the epidemiological and environmental similarities of OCPD and lung cancer. They cite the specific objectives as well as the recommended research approaches to collect better epidemiological data.

Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence of tumours in two of three main endocrine tissue types: parathyroid, pituitary and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was found to occur in three large kindreds, with more prolactinomas and fewer gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing features from the MEN1 gene (e.g. larger pituitary tumours). They also show various expressions of tumour multiplicity; however, pituitary tumour in MEN1 is usually solitary. Diagnosis in MEN1 carriers during childhood is not directed at cancers but at benign morbid tumours. Morbid prolactinoma occurred at the age of 5 years in one MEN1 individual; hence, this is the earliest age at which to recommend tumour surveillance in carriers. The MEN1 gene shows biallelic inactivation in 30% of some types of common variety endocrine tumours (e.g. parathyroid adenoma, gastrinoma, insulinoma and bronchial carcinoid), but in only 1–5% of common pituitary tumours. Heterozygous knockout of MEN1 in mice provides a robust model of MEN1 and has been found to support further research on anti-angiogenesis therapy for pituitary tumours. The rarity of MEN1 mutations in some MEN1-like states aids the identification of other mutated genes, such as AIP, HRPT2 and p27Kip1. We present recent clinical and basic findings about the MEN1 gene, particularly concerning hereditary vs. common variety pituitary tumours. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease (COPD), and lung cancer risk. A study reports that lung cancer risk among α1ATD carriers is seventy percent higher than noncarriers. The effects of tobacco smoke exposure largely contribute to a higher risk of lung cancer. Chronic obstructive pulmonary disease is derived by air-way pollution and results from emphysema and chronic bronchitis. This shows to be an independent risk factor for lung cancer but not so clear if in the same level with that of α1ATD carriers.

Objective: To compare the dental development and rate of tooth development between children with and without cleft lip and palate. Patients: Age- and gender-matched pairs (231 in all) of southern Chinese children ages 3 to 12 years, with and without cleft lip and palate. Methods: Dental histories and radiographs were studied. From these, dental development was determined. Results: Of 2946 tooth pairs in the children with cleft lip and palate, 252 (8.6%) were found to be asymmetric, significantly (p < .001) more than the 63 of 3179 (2.0%) tooth pairs observed in the children without cleft lip and palate. The teeth with the highest frequency of asymmetry were the maxillary lateral incisors (38.1%). Differences in dental development on the cleft versus noncleft sides of children with unilateral cleft lip and palate were significant for both maxillary and mandibular teeth (p < .001 and p = .039, respectively). The mean delay in tooth formation of the children with cleft lip and palate was 4.4 months relative to the children without cleft lip and palate. The majority of the teeth in the cleft lip and palate group were delayed by one developmental stage. This happened in 40.0% of the maxillary teeth and 30.1% of the mandibular teeth. The delay in tooth formation increased as the number of missing teeth increased in the children with cleft lip and palate, although not significantly. Conclusions: This group of southern Chinese children with cleft lip and palate demonstrated a higher prevalence of asymmetric and delayed dental development than did their counterparts who did not have cleft lip and palate. [ABSTRACT FROM AUTHOR]

Abstract  Approximately 5–10% of neuroendocrine tumors (NETs) of the gastroenteropancreatic system (GEP) have a hereditary background. The known inherited syndromes include multiple endocrine neoplasia type 1, neurofibromatosis type 1, von Hippel–Lindau disease, and the tuberous sclerosis complex. This review discusses for each of these syndromes the: (1) involved genes and specific types of mutations, (2) disease prevalence and penetrance, (3) affected neuroendocrine tissues and related clinical syndromes, (4) special morphological features of NETs and their putative precursor lesions. In addition, GEP-NETs clustering in individual families or associated with other malignancies without known genetic background are discussed. [ABSTRACT FROM AUTHOR]

The Pittsburgh Oral-Facial Cleft study was begun in 1993 with the primary goal of identifying genes involved in nonsyndromic orofacial clefts in a variety of populations worldwide. Based on the results from a number of pilot studies and preliminary genetic analyses, a new research focus was added to the Pittsburgh Oral-Facial Cleft study in 1999: to elucidate the role that associated phenotypic features play in the familial transmission patterns of orofacial clefts in order to expand the definition of the nonsyndromic cleft phenotype. The purpose of this paper is to provide a comprehensive review of phenotypic features associated with nonsyndromic orofacial clefts. These features include fluctuating and directional asymmetry, non-right-handedness, dermatoglyphic patterns, craniofacial morphology, orbicularis oris muscle defects, dental anomalies, structural brain and vertebral anomalies, minor physical anomalies, and velopharyngeal incompetence. [ABSTRACT FROM AUTHOR]

Study objective: To describe the relationship between cigarette smoking and quality of life (QOL) among lung cancer survivors as measured by the lung cancer symptom scale (LCSS). Design and setting: The LCSS was mailed to eligible patients (1,506 patients) between 1999 and 2002. LCSS scores (total and individual QOL components) were compared among different groups of cigarette smokers via univariate independent group testing and multivariate linear models. The modeling process examined group differences adjusted for age, gender, stage, and lime of LCSS assessment. LCSS scores were transformed onto a scale of 0 to 100 points in which higher LCSS scores corresponded to a lower QOL. A 10-point difference between groups was defined a priori as being clinically significant. Results: At the lime of lung cancer diagnosis, 18% of the patients were never-smokers, 58% were former smokers, and 24% were current smokers. Among survey respondents completing the LC SS at follow-up assessment (1,028 respondents), the mean age was 65.2 years (SD, 10.8 years) and 45% were women. Thirty percent of baseline current smokers continued to smoke at the lime of the follow-up assessment (ie, persistent smokers). The adjusted mean total LCSS scores for never-smokers and persistent smokers were 17.6 (SD, 4.02) and 28.7 (SD, 5.09), respectively (p <0.0001). Seven of the individual LC SS QOL components (ie, appetite, fatigue, cough, shortness of breath, lung cancer symptoms, illness affecting normal activities, and overall QOL) were clinically and statistically (p < 0.001) different between never-smokers and persistent smokers. No clinically significant differences were noted for pain or hemoptysis. Former smokers had intermediate LCSS scores. No dose-response trends were observed between the number of packs of cigarettes smoked per day or the total number of pack-years smoked and the adjusted scores. Conclusion: The hypothesized relationship between smoking status and QOL was supported by this correlational study. Our findings suggest that persistent cigarette smoking after a lung cancer diagnosis negatively impacts QOL scores. [ABSTRACT FROM AUTHOR]

Chronic inflammation predisposes toward many types of cancer. Chronic bronchitis and asthma, for example, heighten the risk of lung cancer. Exactly which inflammatory mediators (e.g., oxidant species and growth factors) and lung wound repair processes (e.g., proangiogenic factors) enhance pulmonary neoplastic development is not clear. One approach to uncover the most relevant biochemical and physiological pathways is to identify genes underlying susceptibilities to inflammation and to cancer development at the same anatomic site. Mice develop lung adenocarcinomas similar in histology, molecular characteristics, and histogenesis to this most common human lung cancer subtype. Over two dozen loci, called Pas or pulmonary adenoma susceptibility, Par or pulmonary adenoma resistance, and Sluc or susceptibility to lung cancer genes, regulate differential lung tumor susceptibility among inbred mouse strains as assigned by QTL (quantitative trait locus) mapping. Chromosomal sites that determine responsiveness to proinflammatory pneumotoxicants such as ozone (O3), particulates, and hyperoxia have also been mapped in mice. For example, susceptibility QTLs have been identified on chromosomes 17 and 11 for O3-induced inflammation (Inf1, Inf2), O3-induced acute lung injury (Aliq3, Aliq1), and sulfate-associated particulates. Sites within the human and mouse genomes for asthma and COPD phenotypes have also been delineated. It is of great interest that several susceptibility loci for mouse lung neoplasia also contain susceptibility genes for toxicant-induced lung injury and inflammation and are homologous to several human asthma loci. These QTLs are described herein, candidate genes are suggested within these sites, and experimental evidence that inflammation enhances lung tumor development is provided. [ABSTRACT FROM AUTHOR]

Objectives: While 75-90% of people who develop lung cancer are smokers, only a small proportion of smokers develop lung cancer. Identifying factors that increase a smoker's risk of developing lung cancer may help scientists to better understand the etiology of lung cancer and more effectively target high-risk groups for screening. [ABSTRACT FROM AUTHOR]

The bilaterally symmetric body plan of vertebrates features several consistent asymmetries in the placement, structure, and function of organs such as the heart, intestine, and brain. Deviations from the normal pattern result in situs inversus, isomerisms, or heterotaxia (independent randomization), which have significant clinical implications. The invariance of the left-right (LR) asymmetry of normal morphology, neuronal function, and phenotype of several syndromes raises fascinating and fundamental questions in cell, developmental, evolutionary, and neurobiology. While a pathway of asymmetrically expressed signaling factors has been well-characterized in several model systems, very early steps in the establishment of LR asymmetry remain poorly understood. In particular, the origin of consistently oriented asymmetry is unknown. Recently, a candidate for the origins of asymmetry has been suggested: bulk transport of extracellular morphogens by rotating primary cilia during gastrulation. This model is appealing because it 'bootstraps' morphological asymmetry of the embryo from the intrinsic structural (molecular) chirality of motile cilia. However, conceptual and practical problems remain with this hypothesis. Indeed, the genetic data are also consistent with a different mechanism: cytoplasmic transport roles of motor proteins. This review outlines the progress and remaining questions in the field of left-right asymmetry, and focuses on an alternative model for 'Step 1' of asymmetry. More specifically, based on wide-ranging data on ion fluxes and motor protein function in several species, it is suggested that laterality is driven by pH/voltage gradients across the midline, which are established by chiral movement of motor proteins with respect to the cytoskeleton. [ABSTRACT FROM AUTHOR]

Pulmonary carcinoid tumors are neuroendocrine malignant tumors that make up 1% to 2% of all lung tumors. According to histopathologic criteria, carcinoids can be divided into typical (TC) and atypical (AC) carcinoids. Carcinoids can be placed in a spectrum of neuroendocrine tumors, ranging from low-grade malignant TC to intermediate AC to high-grade large-cell neuroendocrine carcinoma and small-cell lung carcinoma. Familial pulmonary carcinoids are rare. The most common symptoms are hemoptysis, cough, recurrent pulmonary infection, fever, chest discomfort and chest pain, unilateral wheezing, and shortness of breath. Paraneoplastic syndromes are rare and include carcinoid syndrome, Cushing’s syndrome, and ectopic growth hormone–releasing hormone secretion. The diagnosis is usually established by flexible bronchoscopy and biopsy, although occasionally this can result in severe hemorrhage. Immunoscintigraphy by somatostatin analogs can also be useful in diagnosis. The treatment of choice is surgical resection, and prognosis is relatively good in TC, although it is worse in AC. The role of radiotherapy and chemotherapy as part of multimodality treatment or palliation is still debated. [ABSTRACT FROM AUTHOR]

Background: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection.Methods: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study.Results: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively).Conclusion: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients. [ABSTRACT FROM AUTHOR]