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Eosinophilia as Initial Presentation of Occult MalignancyMohammadi, Oranus, MD, Sinha, Alok, Bhat, Alina, Jaishankar, Devapiran 07 April 2022 (has links)
Eosinophilia is not an uncommon finding on a routine complete blood count (CBC) during a primary care visit. The differential diagnosis is varied including allergic/atopic disease, drug reaction, infection, inflammatory conditions, and malignancy.
An 80-year-old male was incidentally found to have leukocytosis on routine labs. White blood cell (WBC) was 27.5 K/ul with eosinophilia 4.3 K/ul (normal range 0-0.6 Kul) and Hemoglobin/Platelet counts were normal. Patient was asymptomatic. Denied history of medication change or allergy. Chest X-Ray (CXR) followed by Computed tomography (CT) showed 5 cm pulmonary mass with mediastinal lymphadenopathy. Patient developed progressively enlarging left neck mass, hoarseness, weight loss and decreased appetite in the next 3 weeks. WBC increased steeply to 65 K/ul with eosinophil count - 18.5 K/ul. CT neck revealed a large heterogeneous mass of the thyroid extending to the trachea, esophagus, and mediastinum. Patient decided not to proceed with further diagnostic workup and management given his age and comorbidities.
Eosinophilia can be asymptomatic or present with nonspecific symptoms like cough, fatigue, skin rash or neuropathy. Eosinophilia work up starts with a comprehensive history detailing travel history, exposure to well water/spring water, analysis of past medical history to include asthma, atopy and especially medication history. Physical exam with attention to atopy/eczema and skin rash is vital. Work up may include a CBC, peripheral blood smear, stool test (for ova and parasite), IgE/tryptase levels and evaluation for occult malignancy (CXR is an ideal first step). Further testing with Bone marrow biopsy and CT scans is a consideration if a clear diagnosis is not achieved. Life-threatening complications of untreated hyper-eosinophilia include thromboembolism, endomyocardial fibrosis, cognitive disturbances, and respiratory failure. Incidence of eosinophilia is 1% in malignant tumors. Malignancy encompasses hematological cancers (acute leukemia, chronic myeloid leukemia, systemic mastocytosis, lymphoid neoplasms) and solid tumors (lung, thyroid, breast and gastrointestinal tract cancers). Eosinophilia suggests advanced disease in solid tumors and portends poor prognosis.
Paraneoplastic eosinophilia has been reported in thyroid cancer (sclerosing muco-epidermoid) and lung cancer (squamous and adenocarcinoma). Pathophysiology of eosinophilia in solid tumors is related to bone marrow stimulation through cytokines (interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-2). Primary eosinophilia responds to steroids and hydroxyurea. Treating the underlying malignancy is the cornerstone of paraneoplastic eosinophilia management. We present a case of extreme progressive eosinophilia secondary to a malignancy which would be of interest to the primary care clinician.
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Vergleichende Mutationsanalyse des k-ras-Genes in zytologischen Untersuchungsmaterialien bei nichtkleinzelligen LungenkarzinomenMundt, Thomas 07 June 2012 (has links)
Die vorliegende Arbeit beschäftigte sich mit der Frage, inwieweit zytologische Untersuchungsmaterialien von Patienten mit nichtkleinzelligen Lungenkarzinomen geeignet sind, zur molekularbiologischen Analyse möglicher Mutationen des k-ras-Genes verwendet zu werden. Dafür wurden vier spezifische Polymerasekettenreaktionen mit anschließenden Restriktionsfragmentlängenpolymorphismus-Analysen kreiert und optimiert. In der Folge wurden die k-ras-Mutationen in den verschiedenen Codons nach einer Agarose-Gelelektrophorese unter der UV-Kamera detektiert. Es wurden vergleichende Untersuchungen mit Materialien tumorfreien Gewebes durchgeführt. Ebenso wurden, um die Eignung des zytologischen Materiales zur k-ras-Mutationsdiagnostik nachzuweisen, Mutationsanalysen in histologischem Material durchgeführt und dieses mit den zytologischen Proben derselben Patienten verglichen. Weiterhin wurden bestimmte Korrelationen des k-ras-Mutationsstatus der Patienten mit individuellen und klinischen Parametern analysiert und mit aus der Literatur bekannten Aussagen verglichen.
Es ist bekannt, dass k-ras-Mutationen im Tumor bei Patienten mit fortgeschrittenen nichtkleinzelligen Lungenkarzinomen negative Prädiktoren für einen möglichen Erfolg einer Rezeptortyrosinkinaseinhibitor-Therapie darstellen und die Prognose der Erkrankung verschlechtern. Neuartige Therapiekonzepte scheinen aber auch eine Möglichkeit zu bieten, Patienten mit nachgewiesener k-ras-Mutation eine Therapiealternative ermöglichen zu können. Die vorliegende Arbeit liefert einen wichtigen Beitrag um eine einfache Methode zur Analyse von k-ras-Mutationen bei Patienten mit nichtkleinzelligen Lungenkarzinomen zu finden und damit eine Entscheidung über etwaige weitere Therapieoptionen zu erleichtern.
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HSPA12B: A Novel Facilitator of Lung Tumor GrowthMa, He, Lu, Ting, Zhang, Xiaojin, Li, Chuanfu, Xiong, Jingwei, Huang, Lei, Liu, Ping, Li, Yuehua, Liu, Li, Ding, Zhengnian 01 January 2015 (has links)
Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B (HSPA12B) is a recently identified regulator of expression of proangiogenic factors. However, whether HSPA12B plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing HSPA12B (Tg) and wildtype littermates (WT) were implanted with Lewis lung cancer cells to induce lung tumorigenesis. Tg mice showed significantly higher number and bigger size of tumors than WT mice. Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT tumors. Interestingly, a significantly enhanced upregulation of Cox-2 was detected in Tg tumors than in WT tumors. Also, Tg tumors demonstrated upregulation of VEGF and angiopoietin-1, downregulation of AKAP12, and increased eNOS phosphorylation compared with WT tumors. Celecoxib, a selective Cox-2 inhibitor, suppressed the HSPA12B-induced increase in lung tumor burden. Moreover, celecoxib decreased angiogenesis and proliferation whereas increased apoptosis in Tg tumors. Additionally, celecoxib reduced angiopoietin-1 expression and eNOS phosphorylation but increased AKAP12 levels in Tg tumors. Our results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.
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Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung CarcinomaWang, Ling, Sparks-Wallace, Ayrianna, Casteel, Jared L., Howell, Mary E.A., Ning, Shunbin 31 March 2021 (has links)
Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), with a considerable contribution from its promoter methylation rather than its gene mutations. The Limd1 gene undergoes mutation only at a low rate in NSCLC (0.712%). We have further identified LIMD1-associated molecular signatures in NSCLC, including its natural antisense long non-coding RNA LIMD1-AS1 and a pool of membrane trafficking regulators. We have also identified a subgroup of tumor-infiltrating lymphocytes, especially neutrophils, whose tumor infiltration levels significantly correlate with LIMD1 level in both LUAD and LUSC. However, a significant correlation of LIMD1 with a subset of immune regulatory molecules, such as IL6R and TAP1, was only found in LUAD. Regarding the clinical outcomes, LIMD1 expression level only significantly correlates with the survival of LUAD (p0.1) patients. These findings indicate that LIMD1 plays a survival role in LUAD patients at least by acting as an immune regulatory protein. To further understand the mechanisms underlying the tumor-suppressing function of LIMD1 in NSCLC, we show that LIMD1 downregulation remarkably correlates with the deregulation of multiple pathways that play decisive roles in the oncogenesis of NSCLC, especially those mediated by EGFR, KRAS, PIK3CA, Keap1, and p63, in both LUAD and LUSC, and those mediated by p53 and CDKN2A only in LUAD. This study has disclosed that LIMD1 can serve as a survival prognostic marker for LUAD patients and provides mechanistic insights into the interaction of LIMD1 with NSCLC, which provide valuable information for clinical applications.
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Lung Cancer in WomenGraham, Pamela D., Thigpen, S. Calvin, Geraci, Stephen A. 01 October 2013 (has links)
Lung cancer is the deadliest cancer in women. In the last decade, the first measurable decline in disease-related mortality has occurred and in the last 5 years, the first decline in lung cancer incidence in women in the United States has been reported. Five-year survival rates are much higher in early-stage disease, making effective screening a priority. Data on screening with low-dose computed tomography are controversial; existing guidelines are not sex specific and recommend testing only for patients at high risk for the disease. Although cigarette smoking remains the predisposing factor that is most often associated with tumor development, the advent of molecularly targeted therapy and the growing evidence that susceptible targets are more prevalent in never-smoking women have brought more attention to this particular subpopulation. Studies of both surgery and systemic therapy suggest that not only never-smoking women but also women overall experience better outcomes than men. Identifying all of the factors contributing to these sex differences presents us with an opportunity to identify potentially a distinct tumor biology in women who would warrant a distinct personalized treatment approach.
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Lung Cancer in WomenGraham, Pamela D., Thigpen, S. Calvin, Geraci, Stephen A. 01 October 2013 (has links)
Lung cancer is the deadliest cancer in women. In the last decade, the first measurable decline in disease-related mortality has occurred and in the last 5 years, the first decline in lung cancer incidence in women in the United States has been reported. Five-year survival rates are much higher in early-stage disease, making effective screening a priority. Data on screening with low-dose computed tomography are controversial; existing guidelines are not sex specific and recommend testing only for patients at high risk for the disease. Although cigarette smoking remains the predisposing factor that is most often associated with tumor development, the advent of molecularly targeted therapy and the growing evidence that susceptible targets are more prevalent in never-smoking women have brought more attention to this particular subpopulation. Studies of both surgery and systemic therapy suggest that not only never-smoking women but also women overall experience better outcomes than men. Identifying all of the factors contributing to these sex differences presents us with an opportunity to identify potentially a distinct tumor biology in women who would warrant a distinct personalized treatment approach.
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Association of Education & Amp; Lifestyle Factors With the Perception of Genetic Knowledge on the Development of Lung CancerWang, Liang, Wang, Kesheng, Liu, Xuefeng, He, Yi 01 May 2016 (has links)
Background & objectives: The perception of genetic knowledge is useful for improving the heath behaviour change against developing cancers. However, no studies have investigated the perception of genetic knowledge on the development of lung cancer. The aim of this study was to examine demographic and lifestyle factors of the perception of genetic knowledge on the development of lung cancer. Methods: Data on 2,295 US adults (739 had the perception of genetic knowledge) were taken from the 2003 Health Information National Trends Survey. Multiple logistic regression models were used to evaluate potential factors of the perception of genetic knowledge of lung cancer. Results: Participants aged ≥65 yr were more likely to have the perception of genetic knowledge than those aged 18-44 yr (OR=1.77, 95% CI=1.27-2.46). Higher education was associated with a greater perception of genetic knowledge (OR=1.47, 95% CI=1.16-1.87). Subjects with correct smoking attitude were more than three times more likely to have the perception of genetic knowledge (OR=3.15, 95% CI=2.10-4.72). Subjects with exercise were at an increased likelihood of having the perception of genetic knowledge than those without exercise (OR=1.63, 95% CI=1.24-2.13). Interpretation & conclusions: Positive associations were observed between education and lifestyle factors and the perception of genetic knowledge on the development of lung cancer among US adults. Strategies developed to improve the perception of genetic knowledge of lung cancer may target on individuals who are young, less educated, and lack correct smoking attitude or exercise.
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Depression May Mediate the Relationship Between Sense of Coherence and Quality of Life in Lung Cancer PatientsFloyd, Andrea, Dedert, Eric, Ghate, Sameer, Salmon, Paul, Weissbecker, Inka, Studts, Jamie L., Stetson, Barbara, Sephton, Sandra E. 01 March 2011 (has links)
Lung cancer patients generally experience high levels of physical and psychological distress and decreased quality of life (QOL). Sense of coherence (SOC) has been conceptualized as a personality orientation reflecting the degree to which an individual perceives their world as comprehensible, manageable and meaningful. The present study investigated the associations of SOC with QOL in lung cancer. It also examined potential psychological mediators by which SOC may exert its influences on QOL. Fifty-six participants with non-small cell lung cancer were administered self-report assessments of SOC, QOL and psychological distress. Results revealed that SOC was positively associated with QOL and this relationship may be mediated by depressive symptoms. The current study supports the notion that SOC may be a protective factor with regard to psychological adjustment and QOL in cancer survivors.
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The Role of NOTCH1 in Lung CancerSinicropi-Yao, Sara Lu-Ming 27 July 2018 (has links)
No description available.
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Rôle de l'exposition professionnelle aux agents biologiques dans les cancers broncho-pulmonaires : Analyse de l'étude cas-témoins Icare / Role of Occupational Exposure to Biological Agents in Lung Cancers : Results of the Case-Control Study ICAREBen khedher, Soumaya 06 November 2017 (has links)
Contexte : Le cancer du poumon est le cancer le plus associé aux expositions professionnelles. Bien que l’amiante soit sans doute le facteur étiologique professionnel le plus connu, plusieurs éléments suggèrent également l’implication de facteurs modifiables d’origine environnementale ou professionnelle, beaucoup plus rarement étudiés, parmi lesquels les agents biologiques. Si les endotoxines - toxines situées dans la membrane externe des bacilles Gram négatif - sont fréquemment associées à une réduction du risque de cancer du poumon, les infections à papillomavirus humains sont suspectées d’augmenter ce risque. Les résultats des études épidémiologiques sur le sujet sont divergents et sont régulièrement limités par de nombreuses faiblesses méthodologiques incluant entre autres la non prise en compte du tabagisme et de l’exposition à l’amiante.Objectifs : L’objectif de cette thèse est d’étudier le rôle des agents biologiques présents sur les lieux de travail dans la survenue des cancers broncho-pulmonaires. Plus spécifiquement, les objectifs de ce travail sont : (1) d’étudier le rôle de l’exposition professionnelle aux endotoxines sur le risque de cancer du poumon, d’évaluer les aspects de la relation dose-effet ainsi que les interactions possibles avec les antécédents des maladies respiratoires; (2) de s’intéresser plus particulièrement à l’industrie textile, source de fortes expositions aux endotoxines, en étudiant le risque de cancer du poumon associé à l’exposition professionnelle aux poussières textiles ; (3) d’étudier le risque de cancer du poumon dans l’industrie de la viande en testant, notamment l’hypothèse d’une exposition à un agent viral.Population et méthodes : Ce travail s’est appuyé sur les données de l’étude cas-témoins en population générale ICARE. Les cas de cancer du poumon ont été identifiés dans 10 départements français abritant un registre général de cancer. Au total, 2276 cas de cancer du poumon et 2780 témoins hommes ont été inclus ainsi que 650 cas de cancers du poumon et 775 témoins femmes. Les descriptions détaillées de l’histoire professionnelle complète recueillies par des questionnaires standardisés ont permis de coder les professions et les secteurs d’activités de chaque emploi selon les classifications CITP 1968 et NAF 2000.Résultats : Nous avons trouvé une association inverse entre les expositions professionnelles aux endotoxines et le risque de cancer du poumon particulièrement plus marquée chez les travailleurs de l’élevage (tous types) et de la collecte et traitements des déchets. Les odds ratios de cancer du poumon diminuent avec la durée et l’indice cumulé d’exposition aux endotoxines. Nos résultats ne soutiennent pas l'existence d'une forte association entre l'exposition professionnelle aux poussières textiles et le cancer du poumon, néanmoins, ils montrent une diminution significative de 30% du risque de cancer du poumon chez les travailleurs du coton avec OR= 0,7 ; IC 95% [0,5-0,9]. Par ailleurs, nous observons une association positive significative avec le risque de cancer du poumon chez les travailleurs de l’industrie de la viande (OR= 1,46 [1,0-2,1]). Cependant, les antécédents de verrues de la main ne semblent pas avoir d’effet modificateur dans l’association entre le travail dans l’industrie de la viande et le risque de cancer du poumon.Conclusion : Nos résultats soutiennent le rôle important des expositions professionnelles comme déterminants du risque de cancer du poumon. Ils confirment les associations inverses entre les expositions aux endotoxines et le risque de cancer du poumon suggérant fortement l’hypothèse d’un effet anti-tumoral des endotoxines vis-à-vis du poumon. Par ailleurs, ils semblent indiquer que le travail dans l’industrie de la viande est une situation d’exposition à risque de cancer du poumon sans toutefois conclure formellement quant à l’implication des infections à papillomavirus humains. / Background: Lung cancer is the most common cancer associated with occupational exposures. Although asbestos is the best known occupational etiologic factor, several hypotheses suggest the involvement of some environmental or occupational modifiable factors, much more rarely studied, including biological agents. Endotoxins-toxins being part of the outer membrane of Gram-negative bacilli- are commonly associated with reduced risk of lung cancer, while human papillomavirus infections are suspected of increasing the risk. However, the majority of published studies had small numbers of cases and some methodological issues such as inadequate adjustment for tobacco smoking and occupational exposure to asbestos.Objectives: The aim of the present work is to study the role of biological agents found in the workplace on lung cancer risk and more specifically: (1) to investigate the role of occupational exposure to endotoxins on lung cancer risk, to assess dose-response relationship aspects and possible interactions with history of respiratory disease; (2) to focus on the textile industry, which is a source of high exposure to endotoxins, by examining the risk of lung cancer associated with occupational exposure to textile dust; (3) to study the risk of lung cancer in the meat industry by testing the hypothesis of an exposure to a viral agent.Population and methods: This work was based on a large population-based case-control study, ICARE. Cases and controls were recruited from 10 French departments. Incident cases were identified through French cancer registries. A total of 2,926 lung cancer cases (2,276 men and 650 women) and 3,555 controls (2,780 men and 775 women) were included. Detailed information on lifetime occupation was collected through standardized questionnaires. Jobs and sectors were coded according to the ISCO 1968 and the NAF 2000 classifications.Results: Our results showed an inverse association between exposure to endotoxins and lung cancer risk particularly among livestock (all types) and waste collection and treatment workers. Negative trends were shown with duration and cumulative exposure. Furthermore, our findings do not the existence of strong association between occupational exposure to textile dust and lung cancer. A decreased risk was suggested for distant exposures and for work with cotton fibres (OR = 0.7; 95% CI [0.5-0.9]). On the other hand, we observe a significantly increased risk among meat workers OR = 1.46 [1.1-2.1]). However, the history of hand warts does not seem to have any modifying effect on the association between work in the meat industry and the risk of lung cancer.Conclusion: Our findings support the important role of occupational exposures as a determinant of lung cancer risk. This confirms the inverse associations between endotoxin exposures and the risk of lung cancer strongly suggesting an anti-tumor effect of endotoxins towards the lung. This also seems to indicate that working in the meat industry is a risky situation for lung cancer without, however, formally concluding about the involvement of human papillomavirus infections.
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