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Sample records for spontaneous lung tumors

  1. Systems toxicology approaches enable mechanistic comparison of spontaneous and cigarette smoke-related lung tumor development in the A/J mouse model.

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    Luettich, Karsta; Xiang, Yang; Iskandar, Anita; Sewer, Alain; Martin, Florian; Talikka, Marja; Vanscheeuwijck, Patrick; Berges, An; Veljkovic, Emilija; Gonzalez-Suarez, Ignacio; Schlage, Walter; Hoeng, Julia; Peitsch, Manuel

    2014-06-01

    The A/J mouse is highly susceptible to lung tumor induction and has been widely used as a screening model in carcinogenicity testing and chemoprevention studies. However, the A/J mouse model has several disadvantages. Most notably, it develops lung tumors spontaneously. Moreover, there is a considerable gap in our understanding of the underlying mechanisms of pulmonary chemical carcinogenesis in the A/J mouse. Therefore, we examined the differences between spontaneous and cigarette smoke-related lung tumors in the A/J mouse model using mRNA and microRNA (miRNA) profiling. Male A/J mice were exposed whole-body to mainstream cigarette smoke (MS) for 18 months. Gene expression interaction term analysis of lung tumors and surrounding non-tumorous parenchyma samples from animals that were exposed to either 300 mg/m(3) MS or sham-exposed to fresh air indicated significant differential expression of 296 genes. Ingenuity Pathway Analysis(®) (IPA(®)) indicated an overall suppression of the humoral immune response, which was accompanied by a disruption of sphingolipid and glycosaminoglycan metabolism and a deregulation of potentially oncogenic miRNA in tumors of MS-exposed A/J mice. Thus, we propose that MS exposure leads to severe perturbations in pathways essential for tumor recognition by the immune system, thereby potentiating the ability of tumor cells to escape from immune surveillance. Further, exposure to MS appeared to affect expression of miRNA, which have previously been implicated in carcinogenesis and are thought to contribute to tumor progression. Finally, we identified a 50-gene expression signature and show its utility in distinguishing between cigarette smoke-related and spontaneous lung tumors.

  2. Systems toxicology approaches enable mechanistic comparison of spontaneous and cigarette smoke-related lung tumor development in the A/J mouse model

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    Luettich Karsta

    2014-06-01

    Full Text Available The A/J mouse is highly susceptible to lung tumor induction and has been widely used as a screening model in carcinogenicity testing and chemoprevention studies. However, the A/J mouse model has several disadvantages. Most notably, it develops lung tumors spontaneously. Moreover, there is a considerable gap in our understanding of the underlying mechanisms of pulmonary chemical carcinogenesis in the A/J mouse. Therefore, we examined the differences between spontaneous and cigarette smokerelated lung tumors in the A/J mouse model using mRNA and microRNA (miRNA profiling. Male A/J mice were exposed whole-body to mainstream cigarette smoke (MS for 18 months. Gene expression interaction term analysis of lung tumors and surrounding nontumorous parenchyma samples from animals that were exposed to either 300 mg/m3 MS or sham-exposed to fresh air indicated significant differential expression of 296 genes. Ingenuity Pathway Analysis® (IPA® indicated an overall suppression of the humoral immune response, which was accompanied by a disruption of sphingolipid and glycosaminoglycan metabolism and a deregulation of potentially oncogenic miRNA in tumors of MS-exposed A/J mice. Thus, we propose that MS exposure leads to severe perturbations in pathways essential for tumor recognition by the immune system, thereby potentiating the ability of tumor cells to escape from immune surveillance. Further, exposure to MS appeared to affect expression of miRNA, which have previously been implicated in carcinogenesis and are thought to contribute to tumor progression. Finally, we identified a 50-gene expression signature and show its utility in distinguishing between cigarette smoke-related and spontaneous lung tumors

  3. Spontaneous Tumor Lysis Syndrome

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    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  4. Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model.

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    Hershey, A E; Kurzman, I D; Forrest, L J; Bohling, C A; Stonerook, M; Placke, M E; Imondi, A R; Vail, D M

    1999-09-01

    This study represents part of an effort to determine the safety and efficacy of inhaled antineoplastic drugs, using pet dogs with spontaneously arising primary and metastatic lung cancers (including sarcoma, carcinoma, and malignant melanoma) as a model. Dogs received new formulations of either paclitaxel (PTX) or doxorubicin (DOX) by the inhalation route every 2 weeks using a specially designed aerosol device. Response was assessed radiographically using the indices of tumor nodule number and volume measurement of discrete pulmonary nodules. Dogs experiencing progressive disease after two consecutive treatments were crossed over to receive the alternate compound. In 24 dogs, 6 (25%) responses were noted including 5 partial responses (PR) and 1 complete response. These include 4 (22.2%) of 18 responses to DOX and 2 (13.3%) of 15 responses to PTX. Responses were noted with osteosarcoma (including three dogs with metastatic osteosarcoma that had failed prior systemic chemotherapy), liposarcoma, hemangiosarcoma, and undifferentiated sarcoma. One dog with mammary carcinoma experienced a 47% reduction in volume after PTX inhalation, just shy of PR criteria. One dog with liposarcoma is experiencing a long-term (>12 months) stabilization of disease on PTX. To date, no systemic toxicities have been observed with either PTX or DOX inhalations. Local (pulmonary) toxicity was not observed with PTX; however, changes consistent with pneumonitis/fibrosis were observed in some dogs receiving DOX. Only one of these dogs showed clinical signs, which were responsive to steroid and antitussive therapy. These data represent "proof of principle" for the avoidance of systemic toxicity while delivering efficacious local drug levels by the inhalation route.

  5. Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

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    Belinsky, S.A.; Baylin, S.B.; Issa, J.J. [Johns Hopkins Univ., Baltimore, MD (United States)

    1995-12-01

    CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 {sup INK4a} tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized.

  6. Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

    International Nuclear Information System (INIS)

    Belinsky, S.A.; Baylin, S.B.; Issa, J.J.

    1995-01-01

    CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 INK4a tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized

  7. P53 tumor suppressor gene and protein expression is altered in cell lines derived from spontaneous and alpha-radiation-induced canine lung tumors

    International Nuclear Information System (INIS)

    Tierney, L.A.; Johnson, N.F.; Lechner, J.F.

    1994-01-01

    Mutations in the p53 tumor suppressor gene are the most frequently occurring gene alterations in malignant human cancers, including lung cancer. In lung cancer, common point mutations within conserved exons of the p53 gene result in a stabilized form of mutant protein which is detectable in most cases by immunohistochemistry. In addition to point mutations, allelic loss, rearrangements, and deletions of the p53 gene have also been detected in both human and rodent tumors. It has been suggested that for at least some epithelial neoplasms, the loss of expression of wild-type p53 protein may be more important for malignant transformation than the acquisition of activating mutations. Mechanisms responsible for the loss of expression of wild-type protein include gene deletion or rearrangement, nonsense or stop mutations, mutations within introns or upstream regulatory regions of the gene, and accelerated rates of degradation of the protein by DNA viral oncoproteins

  8. Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

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    Leung, F.L.; Park, J.F.; Dagle, G.E.

    1993-06-01

    In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

  9. Neuroendocrine Tumors of the Lung

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    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  10. Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response.

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    Godet, Yann; Fabre, Elizabeth; Dosset, Magalie; Lamuraglia, Michele; Levionnois, Emeline; Ravel, Patrice; Benhamouda, Nadine; Cazes, Aurélie; Le Pimpec-Barthes, Françoise; Gaugler, Beatrice; Langlade-Demoyen, Pierre; Pivot, Xavier; Saas, Philippe; Maillère, Bernard; Tartour, Eric; Borg, Christophe; Adotévi, Olivier

    2012-05-15

    To investigate the presence and impact of spontaneous telomerase-specific CD4 T-cell responses in cancer patients. A multistep approach was used to design novel pan-HLA-DR-restricted peptides from telomerase. T-cell clones isolated from cancer patients were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T-cell response against telomerase was monitored in 84 metastatic non-small cell lung cancer (NSCLC) patients before first-line chemotherapy (CT) using IFN-γ ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase-specific CD4 T immunity on clinical outcome in patients according to their respective response to CT. We described four novel telomerase-derived CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to most commonly found human MHC class II alleles. UCP-specific CD4 T-cell repertoire is present in human and UCP-specific CD4 T-cell clones generated from cancer patients exhibited high avidity and are Th1 polarized. Significant frequency (38%) of naturally occurring UCP-specific T-cell responses were detected before CT in advanced NSCLC but not in healthy volunteers. This response was shown to significantly increase overall survival (OS) of patients responding to CT (Median OS: 53 vs. 40 weeks, P = 0.034). These results show for the first time a potential synergistic effect of telomerase-specific CD4 T-cell response with CT response in NSCLC and underline the potential role of tumor-specific CD4 T-cell response on the efficiency of conventional anticancer therapy. ©2012 AACR.

  11. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

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    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  12. Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

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    Pelosi, Giuseppe; Papotti, Mauro; Rindi, Guido; Scarpa, Aldo

    2014-06-01

    Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations

  13. Stereotactic Body Radiotherapy for Oligometastatic Lung Tumors

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    Norihisa, Yoshiki; Nagata, Yasushi; Takayama, Kenji; Matsuo, Yukinori; Sakamoto, Takashi; Sakamoto, Masato; Mizowaki, Takashi; Yano, Shinsuke; Hiraoka, Masahiro

    2008-01-01

    Purpose: Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term 'oligometastasis' is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors. Methods and Materials: A total of 34 patients with oligometastatic lung tumors were included in this study. The primary involved organs were the lung (n = 15), colorectum (n = 9), head and neck (n = 5), kidney (n = 3), breast (n = 1), and bone (n = 1). Five to seven, noncoplanar, static 6-MV photon beams were used to deliver 48 Gy (n = 18) or 60 Gy (n = 16) at the isocenter, with 12 Gy/fraction within 4-18 days (median, 12 days). Results: The overall survival rate, local relapse-free rate, and progression-free rate at 2 years was 84.3%, 90.0%, and 34.8%, respectively. No local progression was observed in tumors irradiated with 60 Gy. SBRT-related pulmonary toxicities were observed in 4 (12%) Grade 2 cases and 1 (3%) Grade 3 case. Patients with a longer disease-free interval had a greater overall survival rate. Conclusion: The clinical result of SBRT for oligometastatic lung tumors in our institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastases

  14. Experimental rat lung tumor model with intrabronchial tumor cell implantation.

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    Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

    2008-01-01

    The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

  15. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

    International Nuclear Information System (INIS)

    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B.; Gassmann, M.; Roos, M.

    2004-01-01

    Background and purpose: tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. Material and methods: tumor oxygen partial pressure (pO 2 ) measurements were performed with the eppendorf-pO 2 -Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO 2 was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). Results: 15/26 tumors had a pretreatment median pO 2 ≤ 10 mmHg. The pO 2 values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO 2 of initially hypoxic tumors (pretreatment median pO 2 ≤ 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO 2 decreased. Conclusion: hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were ≥ 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic. (orig.)

  16. Radiofrequency Ablation of Lung Tumors

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    ... out of this tunnel. Rotating around you, the x-ray tube and electronic x-ray detectors are located opposite ... to Cancer Therapy (Radiation Oncology) Radiation Dose in X-Ray and CT Exams Chest Tube Placement (Thoracostomy) and Pleurodesis Thoracentesis Lung Cancer Treatment ...

  17. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

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    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B. [Section of Diagnostic Imaging and Radiation Oncology, Veterinary School, Univ. of Zurich (Switzerland); Gassmann, M. [Inst. for Veterinary Physiology, Univ. of Zurich (Switzerland); Roos, M. [Inst. for Social and Preventive Medicine, Univ. of Zurich (Switzerland)

    2004-05-01

    Background and purpose: tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. Material and methods: tumor oxygen partial pressure (pO{sub 2}) measurements were performed with the eppendorf-pO{sub 2}-Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO{sub 2} was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). Results: 15/26 tumors had a pretreatment median pO{sub 2} {<=} 10 mmHg. The pO{sub 2} values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO{sub 2} of initially hypoxic tumors (pretreatment median pO{sub 2} {<=} 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO{sub 2} decreased. Conclusion: hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were {>=} 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic. (orig.)

  18. Thoracoscopic lung lobectomy for treatment of lung tumors in dogs.

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    Lansdowne, Jennifer L; Monnet, Eric; Twedt, David C; Dernell, William S

    2005-01-01

    To report use of thoracoscopic lung lobectomy (TLL) for treatment of lung tumors (LT) in dogs. Retrospective study. Nine dogs. Dogs that had TLL for tumor removal were included. Using general anesthesia and 1-lung ventilation, TLL was performed using a 30-60 mm endoscopic gastrointestinal anastomosis stapler. If the visual field was obscured, lobe resection was completed via thoracotomy. Metastatic and primary LT were resected by thoracoscopic lobectomy in 9 dogs (6 male, 3 female; mean (+/-SD) weight, 29+/-7 kg; mean age, 10.7+/-1.9 years). Six dogs had a solitary mass and 3 dogs had 2 masses within a single lobe. The left caudal lobe was removed in 3 dogs. In 5 dogs, TLL was used alone whereas conversion to thoracotomy was required in 4 dogs because of poor visibility. There were 7 metastatic LT and 2 primary LT. Mean duration of thoracoscopic surgery was 108.8+/-30.3 minutes compared with 150.75+/-55.4 minutes in dogs requiring conversion to thoracotomy. Mean hospitalization was 3.1+/-1.3 days. Provided the visual field is not obscured, TLL can be performed effectively in dogs. Dogs with metastatic or primary LTs should be considered for TLL, particularly for small masses positioned away from the hilus in the left caudal lung lobe.

  19. Tumor to tumor metastasis: Adenocarcinoma of lung metastatic to meningioma

    Directory of Open Access Journals (Sweden)

    A Talukdar

    2014-01-01

    Full Text Available Tumor-to-tumor metastasis (T2Tmets is an established entity but often overlooked and underdiagnosed. Merely 84 such cases are reported in literature till date. The authors here describe a 65-year-old man presenting with first episode of focal seizure and incidentally turned out to be a case of adenocarcinoma of lung metastatic to a meningioma. The diagnosis of T2Tmets was based solely on histopathological criteria. Recent advent of brain imaging revolutionized its diagnosis and it has moved from the realm of thologists to that of radiologists. In our case, diagnosis was also established by immunohistochemistry.

  20. Spontaneous malignant transformation of conventional giant cell tumor

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    Grote, H.J.; Pomjanski, N.; Boecking, A. [Institute of Cytopathology, Heinrich Heine University, Moorenstrasse 5, 40225, Duesseldorf (Germany); Braun, M. [Orthopedic Hospital Volmarstein, University of Witten/Herdecke, Hartmannstrasse 24, 58300, Wetter (Ruhr) (Germany); Kalinski, T.; Roessner, A. [Department of Pathology, Otto von Guericke University, Leipziger Strasse 44, 39120, Magdeburg (Germany); Back, W.; Bleyl, U. [Department of Pathology, Ruprecht Karls University Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer, 68167, Mannheim (Germany)

    2004-03-01

    Spontaneous malignant transformation of conventional giant cell tumor (GCT) of bone is exceedingly rare. We report on a case of GCT of the iliac crest in a 35-year-old woman with malignant change into a high-grade osteosarcoma 10 years after the first appearance of GCT on a radiograph. Since the patient refused therapy for personal reasons the tumor remained untreated until sarcomatous transformation occurred. Image cytometry showed DNA aneuploidy and a suspiciously high 2c deviation index (2cDI) in the primary bone lesion. A thorough review of the world literature revealed only seven fully documented cases of secondary malignant GCT which matched the definition of a ''sarcomatous growth that occurs at the site of a previously documented benign giant cell tumor'' and not treated by radiotherapy. These cases as well as the current one suggest that a spontaneous secondary malignant GCT presents as a frankly sarcomatous tumor in the form of an osteosarcoma or malignant fibrous histiocytoma. It usually appears at sites of typical GCTs - often without any recurrent intermediate state - and is diagnosed 3 or more years after the primary bone lesion. The prognosis is poor. (orig.)

  1. Oncogene expression in primary lung tumors in dogs that inhaled 239PuO2

    International Nuclear Information System (INIS)

    Kelly, G.; Kerkof, P.R.; Haley, P.J.

    1988-01-01

    Ten radiation-induced and three spontaneous lung tumors were analyzed for aberrant expression of known oncogenes. In 12 of 13 tumors tested, sequences hybridizing to the c-myc oncogene were expressed at levels 1.5 times higher than sequences hybridizing to β-actin. This level of oncogene expression was also observed in 9 of 13 tumors for 1 or more members of the ras family of oncogenes. Seven of thirteen tumors examined express sequences that hybridize with clones of v-ros or c-met. The ros and met clones both code for oncogenes whose normal homologues are transmembrane proteins related to the insulin receptor. (author)

  2. Characteristics of the spontaneous gastric endocrine tumor of mastomys

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    Modlin, I.M.; Zucker, K.A.; Zdon, M.J.; Sussman, J.; Adrian, T.E.

    1988-01-01

    Mastomys is a rodent which has been reported to develop spontaneous antral endocrine tumors with acid hypersecretion and duodenal ulceration. This study documents the establishment of a breeding colony and the characterization of the tumors and their possible secretagogues. Parietal cell secretory characteristics were studied using isolated gastric glands (IGG) of both normal (n = 5) and tumor-bearing animals. Tumors (n = 6) and control gastric tissue samples were examined by light transmission microscopy and immunohistochemistry. Gastrin was measured by radioimmunoassay in both plasma and tissue. IGG were prepared by collagenase dispersion and acid sequestration assessed by [ 14 C]AP accumulation. Secretory mechanisms of this species were identified by establishment of a histamine dose-response curve and use of 8-bromo-cAMP. Receptor and proton pump inhibitions were assessed using cimetidine (10(-5)M) and the H/K ATPase inhibitor omeprazole (10(-5]. Both reduced [ 14 C]AP accumulation significantly (P less than 0.05). 8-Bromo-cAMP and histamine significantly stimulated [ 14 C]AP accumulation (P less than 0.05). Although parietal cells were substantially increased in tumor animals as compared to controls, the physiological parameters of acid secretion appeared normal in both and were comparable to other species which have been studied. Tumors were Grimelius positive and contained diffuse electron-dense granules. Immunohistochemistry was negative for gastrin, bombesin, serotonin, neuron-specific enolase, calcitonin, and pancreatic polypeptide. Tumor histamine-like immunoreactivity was, however, positive. Normal stomach contained 1001 +/- 185 compared to less than 0.5 pmole/g gastrin in tumors. Plasma gastrin was normal in both groups (29 +/- 5) as compared to 26 +/- 8 pmole/liter

  3. Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60 Co γ rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from γ-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene. 36 refs., 2 figs., 2 tabs

  4. community acquired pneumonia or βhcg - Producing lung tumor

    African Journals Online (AJOL)

    She developed signs suggestive of βhCG-producing lung tumor with metastasis to the brain and succumbed to the illness before she could be referred for further evaluations and management. Key Words: Community acquired pneumonia, βhCG-producing lung tumor, Paraneoplastic Syndrome, Oculomotor Nerve Palsy.

  5. Computed tomographic appearance of primary lung tumors in dogs.

    Science.gov (United States)

    Marolf, Angela J; Gibbons, Debra S; Podell, Brendan K; Park, Richard D

    2011-01-01

    Canine primary lung tumors typically appear radiographically as a well-circumscribed solitary mass in the periphery of a caudal lung lobe. Consolidated and diffuse forms of primary lung tumors have also been described. Nineteen dogs with computed tomographic (CT) images of the thorax and a histological diagnosis of primary lung tumor (17 primary carcinomas and two primary sarcomas) were evaluated retrospectively to characterize the CT findings. All primary lung tumors were bronchocentric in origin with internal air bronchograms. The bronchi were typically narrowed, displaced, and often obstructed by the tumor. Eighteen of 19 (95%) of the tumors were solitary and there was one pneumonic/alveolar form. Most solitary tumors were well circumscribed (17/18), located in the central to periphery of the lung (14/18), and in a cranial or caudal lobe (16/19). Most primary lung tumors (11/17) had mild to moderate heterogeneous contrast enhancement. Five of 19 dogs (26%) had evidence of pulmonary metastasis. Internal mineralization (3/19) and tracheobronchial lymphadenopathy (4/19) were also identified. On CT examination, solitary, well circumscribed, bronchocentric masses with internal air bronchograms are consistent with a primary pulmonary tumor in dogs. © 2010 Veterinary Radiology & Ultrasound.

  6. Pleural effusion resembling a lung tumor: phantom tumor of the lung

    Directory of Open Access Journals (Sweden)

    Soorih Shaikh

    2016-01-01

    Full Text Available 78-years- old female known case of Congestive Heart failure, with ejection fraction of 55% on recent echocardiograph, presented with complains of Shortness of breath, Cough and sputum without fever. She had stopped taking medications recently and examination showed patient in fluid overload. Conventional postero-anterior Chest radiograph revealed a mass like opacity in lower zone of the right lung while Lateral view radiograph showed cigar shaped opacity due to pleural effusion in oblique fissure of the right lung. Patient was given diuretics on the basis of clinical and radiographic findings and the rounded opacity disappeared on repeat radiograph. Thus the diagnosis of Phantom tumor of lung was made. It is therefore suggested to get a lateral chest radiograph and give a trial of diuretics in such cases before going for other investigations or surgical procedures.

  7. Molecular characterization of radon-induced rat lung tumors

    International Nuclear Information System (INIS)

    Guillet Bastide, K.

    2008-11-01

    The radon gas is a well known lung carcinogenic factor in human at high doses but the cancer risk at low doses is not established. Indeed, epidemiological studies at low doses are difficult to conduct because of the human exposure to other lung carcinogenic factors. These data underlined the necessity to conduct experiments on lung tumors developed on animal model. The aim of this work was to characterize rat lung tumors by working on a series of radon-induced tumors that included adenocarcinomas (A.C.), squamous cell carcinomas (S.C.C.) and adeno-squamous carcinomas (A.S.C.), that are mixed tumors with both A.C. and S.C.C. cellular components. A C.G.H. analysis of the three types of tumors allowed us to define chromosomal recurrent unbalances and to target candidate genes potentially implicated in lung carcinogenesis, as p16Ink4a, p19Arf, Rb1, K-Ras or c-Myc. A more precise analysis of the p16Ink4a/Cdk4/Rb1 and p19Arf/Mdm2/Tp53 pathways was performed and indicated that the Rb1 pathway was frequently inactivated through an absence of p16 Ink4a protein expression, indicating that it has a major role in rat lung carcinogenesis. Finally, a comparative transcriptomic analysis of the three types of tumors allowed us to show for the first time that the complex tumors A.S.C. have a transcriptomic profile in accordance with their mixed nature but that they also display their own expression profiles specificities. This work allowed us to find molecular characteristics common to murine and human lung tumors, indicating that the model of lung tumors in rat is pertinent to search for radiation-induced lung tumors specificities and to help for a better molecular identification of this type of tumors in human. (author)

  8. Dynamic modeling of lung tumor motion during respiration

    Energy Technology Data Exchange (ETDEWEB)

    Kyriakou, E; McKenzie, D R, E-mail: e.kyriakou@physics.usyd.edu.au, E-mail: d.mckenzie@physics.usyd.edu.au [School of Physics, University of Sydney, NSW 2006 (Australia)

    2011-05-21

    A dynamic finite element model of the lung that incorporates a simplified geometry with realistic lung material properties has been developed. Observations of lung motion from respiratory-gated computed tomography were used to provide a database against which the predictions of the model are assessed. Data from six patients presenting with lung tumors were processed to give sagittal sections of the lung containing the tumor as a function of the breathing phase. Statistical shape modeling was used to outline the diaphragm, the tumor volume and the thoracic wall at each breathing phase. The motion of the tumor in the superior-inferior direction was plotted against the diaphragm displacement. The finite element model employed a simplified geometry in which the lung material fills a rectangular volume enabling two-dimensional coordinates to be used. The diaphragm is represented as a piston, driving the motion. Plots of lung displacement against diaphragm displacement form hysteresis loops that are a sensitive indicator of the characteristics of the motion. The key parameters of lung material that determine the motion are the density and elastic properties of lung material and the airway permeability. The model predictions of the hysteresis behavior agreed well with observation only when lung material is modeled as viscoelastic. The key material parameters are suggested for use as prognostic indicators of the progression of disease and of changes arising from the response of the lung to radiation treatment.

  9. Estimation of lung tissue incompressibility variation throughout respiration for tumor targeting in lung radiotherapy

    Science.gov (United States)

    Shirzadi, Zahra; Samani, Abbas

    2013-03-01

    A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Lung tissue incompressibility variation stems from significant air content variation in the tissue throughout respiration. Estimating lung tissue incompressibility and its variation is critical for computer assisted tumor motion tracking. Continuous tumor motion during respiration is a major challenge in lung cancer treatment by external beam radiotherapy. If not accounted for, this motion leads to areas of radiation over dosage for the lung normal tissues. Since no effective imaging modality is available for real-time lung tumor tracking, computer based modeling which has the capability for accurate tissue deformation estimation can be a good alternative. Lung tissue deformation estimation can be made using the lung Finite Element (FE) model where its accuracy depends on input tissue biomechanical properties including incompressibility parameter. In this research, an optimization algorithm is proposed to estimate the incompressibility parameter function in terms of respiration cycle time. In this algorithm, the incompressibility parameter and lung pressure values are varied systematically until optimal values, which result in maximum similarity between acquired and simulated 4D CT images of the lung, are achieved for each respiration time point. The simulated images are constructed using a reference image in conjunction with the deformation field obtained from the lung's FE model in each respiration time increment. We demonstrated that utilizing the calculated function along with respiratory system FE modeling leads to accurate tumor targeting, hence potentially improving lung radiotherapy outcome.

  10. A Genomics-Based Classification of Human Lung Tumors

    NARCIS (Netherlands)

    Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Bogus, Magdalena; Buettner, Reinhard; Perner, Sven; Russell, Prudence; Thunnissen, Erik; Travis, William D.; Brambilla, Elisabeth; Soltermann, Alex; Moch, Holger; Brustugun, Odd Terje; Solberg, Steinar; Lund-Iversen, Marius; Helland, Aslaug; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A.; Chen, Yuan; Groen, Harry; Timens, Wim; Sietsma, Hannie; Clement, Joachim H.; Weder, Walter; Saenger, Joerg; Stoelben, Erich; Ludwig, Corinna; Engel-Riedel, Walburga; Smit, Egbert; Heideman, Danille A. M.; Snijders, Peter J. F.; Nogova, Lucia; Sos, Martin L.; Mattonet, Christian; Toepelt, Karin; Scheffler, Matthias; Goekkurt, Eray; Kappes, Rainer; Krueger, Stefan; Kambartel, Kato; Behringer, Dirk; Schulte, Wolfgang; Galetke, Wolfgang; Randerath, Winfried; Heldwein, Matthias; Schlesinger, Andreas; Serke, Monika; Hekmat, Khosro; Frank, Konrad F.; Schnell, Roland; Reiser, Marcel; Huenerlituerkoglu, Ali-Nuri; Schmitz, Stephan; Meffert, Lisa; Ko, Yon-Dschun; Litt-Lampe, Markus; Gerigk, Ulrich; Fricke, Rainer; Besse, Benjamin; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Moro-Sibilot, Denis; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John K.; Hyde, Russell; Validire, Pierre; Girard, Philippe; Muscarella, Lucia A.; Fazio, Vito M.; Hallek, Michael; Soria, Jean-Charles; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Achter, Viktor; Lang, Ulrich; Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Pao, William; Travis, William D.; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman K.

    2013-01-01

    We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

  11. Lung Tumor Segmentation Using Electric Flow Lines for Graph Cuts

    DEFF Research Database (Denmark)

    Hollensen, Christian; Cannon, George; Cannon, Donald

    2012-01-01

    Lung cancer is the most common cause of cancer-related death. A common treatment is radiotherapy where the lung tumors are irradiated with ionizing radiation. The treatment is typically fractionated, i.e. spread out over time, allowing healthy tissue to recover between treatments and allowing tum...

  12. Giant solitary fibrous tumor of the lung: A case report

    OpenAIRE

    Xiao, Ping; Sun, Linlin; Zhong, Diansheng; Lian, Linjuan; Xu, Dongbo

    2014-01-01

    A solitary fibrous tumor arising from the lung parenchyma is rarely described. Here, we present the clinical, imaging, and histological features of a case of a 54-year-old woman with an incidental lung mass of the right lower lobe on a chest radiograph.

  13. Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression

    International Nuclear Information System (INIS)

    Chen, M.-F.; Keng, Peter C.; Shau Hungyi; Wu, C.-T.; Hu, Y.-C.; Liao, S.-K.; Chen, W.-C.

    2006-01-01

    Purpose: In this study, we examined the role of peroxiredoxin I (Prx I) in lung cancer cell growth in vitro and in vivo and its influence on these tumor cells' sensitivity to radiotherapy. Methods and materials: We established stable transfectants of A549 (p53+) and H1299 (p53-) lung carcinoma cell lines with Prx I antisense to downregulate their Prx I protein. We then examined their in vitro biologic changes and used nude mice xenografts of these cell lines to compare tumor invasion, spontaneous metastatic capacity, and sensitivity to radiotherapy. Results: The Prx I antisense transfectants of both cell lines showed a significant reduction in Prx I protein production. Prx I antisense transfectants grew more slowly than did the wild type. As xenografts in mice, A549 Prx I antisense transfectants showed a threefold delay in the generation of palpable tumors. The incidence of spontaneous metastasis of Prx I antisense transfectants was significantly less than that of the wild-type cells. Furthermore, irradiation of Prx I antisense transfectants caused more than twice the growth delay compared with the wild type. Conclusion: The results of these studies suggest that inactivation of Prx I may be a promising approach to improve the treatment outcome of patients with lung cancer

  14. P53 MUTATIONS IN HUMAN LUNG-TUMORS

    NARCIS (Netherlands)

    MILLER, CW; ASLO, A; KOK, K; YOKOTA, J; BUYS, CHCM; TERADA, M; KOEFFLER, HP; Simon, K.

    1992-01-01

    Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in

  15. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Spontaneous rupture of renal pelvis secondary to ureteral obstruction by urothelial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Daniel Alvarenga; Palma, Ana Laura Gatti; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago Jose; Caserta, Nelson Marcio Gomes, E-mail: daniel_alvafer@yahoo.com.br, E-mail: daniel_alvafer@icloud.com [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Medicina. Dept. de Radiologia

    2014-09-15

    Partial spontaneous rupture of the upper urinary tract is rare and usually associated with nephrolithiasis. Other reported causes, apart from instrumentation and trauma, involve obstructive ureteral tumor in the pelvic cavity, retroperitoneal fibrosis, fluid overload, and pregnancy. We report a case of spontaneous rupture of renal pelvis secondary to ureteral obstruction caused by urothelial tumor, clinically suspected and evaluated by CT scans and MRIs, discussing the relevant findings for diagnosis.(author)

  17. Spontaneous rupture of renal pelvis secondary to ureteral obstruction by urothelial tumor

    International Nuclear Information System (INIS)

    Fernandes, Daniel Alvarenga; Palma, Ana Laura Gatti; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago Jose; Caserta, Nelson Marcio Gomes

    2014-01-01

    Partial spontaneous rupture of the upper urinary tract is rare and usually associated with nephrolithiasis. Other reported causes, apart from instrumentation and trauma, involve obstructive ureteral tumor in the pelvic cavity, retroperitoneal fibrosis, fluid overload, and pregnancy. We report a case of spontaneous rupture of renal pelvis secondary to ureteral obstruction caused by urothelial tumor, clinically suspected and evaluated by CT scans and MRIs, discussing the relevant findings for diagnosis.(author)

  18. [Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

    Science.gov (United States)

    Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

    2017-10-20

    Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

  19. Influence of pretreatment polarographically measured oxygenation levels in spontaneous canine tumors treated with radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bley, C.R.; Ohlerth, S.; Wergin, M.; Achermann, R.; Kaser-Hotz, B. [Section of Diagnostic Imaging and Radiation Oncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Roos, M. [Biostatistics, ISPM, Univ. of Zurich (Switzerland)

    2006-09-15

    Background and purpose: the level of hypoxia in primary tumors has been described to influence response to treatment. The aim of the present study was to investigate the impact of pretreatment oxygen level measurements in spontaneous canine tumors on treatment outcome. Material and methods: data of pretreatment tumor oxygenation status and local tumor response after primary radiation therapy in a group of spontaneously occurring tumors in dogs (n = 52) was collected. Radiation therapy was given with curative (14-17 x 3-3.5 Gy) or palliative intent (3 x 8 Gy or 4-5 x 6 Gy). Progression-free interval and overall survival were correlated to polarographically measured tumor oxygenation status. Results: in the curatively irradiated group, tumors with median p0{sub 2} values {<=} 10 mmHg tended to have shorter median progression-free interval compared to better oxygenated tumors (246 vs. 739 days). The same trend could be shown for overall survival (330 vs. 745 days), indicating a cutoff value in this region. In the group treated with lower doses of radiation, the level of oxygen was no longer found to be of prognostic value; however, in this group hemoglobin had a significant impact on outcome. Conclusion: in curatively irradiated spontaneous canine tumors, tumor hypoxia was found to be a prognostic indicator, independent of tumor histologies and volume. (orig.)

  20. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

    DEFF Research Database (Denmark)

    Knudsen, Mie Grunnet; Sorensen, J B

    2012-01-01

    The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those....... Interestingly, an overweight of low stage (stage I-II) disease and adenocarcinoma (AC) patients were observed in this group. The remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with squamous carcinoma (SQ). One study found evidence for that a tumor marker index (TMI), based...

  1. meta-analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xianfeng LU

    2010-12-01

    Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

  2. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Chapman, Christopher [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of Michigan School of Medicine, Ann Arbor, MI (United States); Rao, Aarti [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Davis, School of Medicine, Davis, CA (United States); Shen, John [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Irvine, School of Medicine, Irvine, CA (United States); Quinlan-Davidson, Sean [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Filion, Edith J. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Departement de Medecine, Service de Radio-Oncologie, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Wakelee, Heather A.; Colevas, A. Dimitrios [Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); Whyte, Richard I. [Department of Cardiothoracic Surgery, Division of General Thoracic Surgery, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); and others

    2012-09-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume {>=}12 mL) received multifraction regimens with BED {>=}100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  3. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    International Nuclear Information System (INIS)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy; Chapman, Christopher; Rao, Aarti; Shen, John; Quinlan-Davidson, Sean; Filion, Edith J.; Wakelee, Heather A.; Colevas, A. Dimitrios; Whyte, Richard I.

    2012-01-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18–25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50–60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  4. Tumors of the lungs and bronchi

    International Nuclear Information System (INIS)

    Juhl, J.H.

    1987-01-01

    There has been an absolute as well as a relative increase in the incidence of carcinoma of the lung in the past 40 years, reflected in the mortality rate. In white male smokers, the reported incidence of cancer of the lung is 15 to 30 times higher than in nonsmokers. Of all carcinomas, bronchogenic carcinoma carries the highest mortality rate, but it may have reached a plateau in males. The incidence and mortality rate in females is now rising, with one study showing a drop in male:female ratio from 15 to 1 in the years 1955 to 1959 to 6 to 1 in the years 1968 to 1971 - a trend that appears to be related to an increase in female smokers. An increase in all cell types of lung cancer occurs in cigarette smoker. There also appears to be an increase in lung cancer in workers exposed to asbestos, arsenic, beryllium, chromate, nickel, vinyl chloride, radon gas, atomic radiation, and bis-chloromethyl ether (BCME). The number of workers studied does not allow a final conclusion about the cell type predominance in these groups

  5. Unusual case of pancreatic inflammatory myofibroblastic tumor associated with spontaneous splenic rupture

    Directory of Open Access Journals (Sweden)

    Hassan Fadi K

    2010-11-01

    Full Text Available Abstract Background Spontaneous splenic rupture considered a relatively rare but life threatening. The three commonest causes of spontaneous splenic rupture are malignant hematological diseases, viral infections and local inflammatory and neoplastic disorders. We describe a unique and unusual case of inflammatory myofibroblastic tumor of the tail of pancreas presented with massively enlarged spleen and spontaneous splenic rupture. Case presentation A 19 years old male patient with no significant past medical history presented to emergency room with abdominal pain and fatigue. Massively enlarged spleen was detected. Hypotension and rapid reduction of hemoglobin level necessitated urgent laparatomy. About 1.75 liters of blood were found in abdominal cavity. A large tumor arising from the tail of pancreas and local rupture of an enlarged spleen adjacent to the tumor were detected. Distal pancreatectomy and splenectomy were performed. To our knowledge, we report the first case of massively enlarged spleen that was complicated with spontaneous splenic rupture as a result of splenic congestion due to mechanical obstruction caused by an inflammatory myofibroblastic tumor of the tail of pancreas. A review of the literature is also presented. Conclusion Inflammatory myofibroblastic tumor of the tail of pancreas should be included in the differential diagnosis of the etiological causes of massively enlarged spleen and spontaneous splenic rupture.

  6. Pancoast tumor or lung tumor upper groove . Case report and literature review

    Directory of Open Access Journals (Sweden)

    R. Puma

    2015-04-01

    Full Text Available Lung cancer is the leading cause of cancer mortality in the world, both men and women. A 75% of patients at diagnosis have some degree of cough, hemoptysis and dyspnea as initial symptoms. Pancoast tumor or superior pulmonary sulcus tumor represents less than 5% of all bronchogenic carcinomas. They are located at the apex of the lung and is mainly characterized by invasion by contiguity of thoracic outlet structures and different from the usual signosintomatología: shoulder pain and / or the ipsilateral arm. We present the case of a male patient of 63 years after attend different services (such as orthopedics, neurology, and speech therapy was diagnosed with Pancoast tumor biopsy of cervical lymphadenopathy. The diagnosis of Pancoast tumor should be suspected at the persistence painful shoulder syndrome in patients over 60 years with a history of smoking. The usual clinical presentation of this type of lung cancer unnecessarily delaying diagnosis and correct treatment.

  7. Lung Tumor Radiofrequency Ablation: Where Do We Stand?

    International Nuclear Information System (INIS)

    Baère, Thierry de

    2011-01-01

    Today, radiofrequency ablation (RFA) of primary and metastatic lung tumor is increasingly used. Because RFA is most often used with curative intent, preablation workup must be a preoperative workup. General anesthesia provides higher feasibility than conscious sedation. The electrode positioning must be performed under computed tomography for sake of accuracy. The delivery of RFA must be adapted to tumor location, with different impedances used when treating tumors with or without pleural contact. The estimated rate of incomplete local treatment at 18 months was 7% (95% confidence interval, 3–14) per tumor, with incomplete treatment depicted at 4 months (n = 1), 6 months (n = 2), 9 months (n = 2), and 12 months (n = 2). Overall survival and lung disease-free survival at 18 months were, respectively, 71 and 34%. Size is a key point for tumor selection because large size is predictive of incomplete local treatment and poor survival. The ratio of ablation volume relative to tumor volume is predictive of complete ablation. Follow-up computed tomography that relies on the size of the ablation zone demonstrates the presence of incomplete ablation. Positron emission tomography might be an interesting option. Chest tube placement for pneumothorax is reported in 8 to 12%. Alveolar hemorrhage and postprocedure hemoptysis occurred in approximately 10% of procedures and rarely required specific treatment. Death was mostly related to single-lung patients and hilar tumors. No modification of forced expiratory volume in the first second between pre- and post-RFA at 2 months was found. RFA in the lung provides a high local efficacy rate. The use of RFA as a palliative tool in combination with chemotherapy remains to be explored.

  8. Radiographic characterization of primary lung tumors in 74 dogs.

    Science.gov (United States)

    Barrett, Laura E; Pollard, Rachel E; Zwingenberger, Allison; Zierenberg-Ripoll, Alexandra; Skorupski, Katherine A

    2014-01-01

    Primary pulmonary neoplasia is well recognized in dogs and prognosis depends upon the tumor type. The purpose of this retrospective study was to characterize the radiographic appearance of different primary lung tumors with the goal of establishing imaging criteria to separate the different types. Three-view thoracic radiographs of 74 dogs with histologically confirmed pulmonary anaplastic carcinoma (n = 2), adenocarcinoma (n = 31), bronchioalveolar carcinoma (n = 19), histiocytic sarcoma (n = 21), and squamous cell carcinoma (n = 1) were evaluated. Radiographs were assessed for tumor volume, affected lobe, location within lobe, overall pulmonary pattern, presence of cavitation, mineralization, air bronchograms, lymphadenomegaly, and pleural fluid. Histiocytic sarcomas were significantly larger than other tumor types (271 cm(3); P = 0.009) and most likely to be found in the left cranial (38%; 8/21) and right middle (43%; 9/21) lung lobes, whereas adenocarcinomas were most likely to be found in the left caudal (29%; 9/31) lung lobe. Fifty-seven percent (12/21) of histiocytic sarcomas had an internal air bronchogram. Findings indicate that a large mass in the periphery or affecting the whole lobe of the right middle or left cranial lung lobe with an internal air bronchogram is likely to be an histiocytic sarcoma. © 2014 American College of Veterinary Radiology.

  9. Capnocytophaga Lung Abscess in a Patient with Metastatic Neuroendocrine Tumor

    OpenAIRE

    Thirumala, Raghu; Rappo, Urania; Babady, N. Esther; Kamboj, Mini; Chawla, Mohit

    2012-01-01

    Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor.

  10. Capnocytophaga lung abscess in a patient with metastatic neuroendocrine tumor.

    Science.gov (United States)

    Thirumala, Raghu; Rappo, Urania; Babady, N Esther; Kamboj, Mini; Chawla, Mohit

    2012-01-01

    Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor.

  11. Combined treatment of syngeneic murine tumors and xenotransplanted human lung cancer by immunotherapy and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Terashima, H.; Yasumoto, K.; Yanagawa, E.; Takayama, K. (Kyushu Cancer Center, Fukuoka (Japan)); Nomoto, K.

    1981-06-01

    The synergistic effect of nonspecific immunotherapy with cell-wall skeleton of BCG on radiotherapy against two syngeneic murine tumors, a methylcho-lanthrene-induced tumor (MCA) and a spontaneous well-differentiated mammary adenocarcinoma (Br-1), was studied in (+/+) BALB/c mice and (nu/nu) mice of BALB/c background. Single irradiation of tumors with a dose of 2000 rad induced complete shrinkage in about 18% of MCA and Br-1 tumors in (+/+) mice. Single irradiation did not induce complete shrinkage of tumors in (nu/nu) mice. When immunotherapy was combined with radiotherapy, the rates of complete shrinkage of MCA and Br-1 tumors increased to 82 and 61%, respectively. In contrast, such a strong synergistic effect was not observed in (nu/nu) mice. Moreover, human lung cancers (two squamous cell carcinomas and two small cell carcinomas) xenotransplanted to nude mice were treated with the combined therapy. The effect was stronger on squamous cell carcinomas than on small cell carcinomas.

  12. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    an immunoglobulin G (IgG)-immune complex to trigger the more efficient FcgR-mediated antigen A B C D E Figure 7. APC-like Hybrid Neutrophils Are Able...CD14+CD86+CD206+CCR7+) (Fig1. B- D ). TCM collected from digested tumors where we did not find hybrid TANs was used to differentiate immature BMN into...ili ty d ye (F V D 6 60 ) none +TCM PBNs and BMNs survival 100 101 102 103 104 100 101 102 103 104 0 5.7 940 none CD15 PBNs day 3 PBNs day

  13. Spontaneous Retroperitoneal Hemorrhage in a Mediastinal Tumor in a Patient With Polymyositis: A Case Report

    Directory of Open Access Journals (Sweden)

    Tzu-Jung Fang

    2008-08-01

    Full Text Available Spontaneous retroperitoneal hemorrhage is a lethal cause of acute abdomen that is most frequently related to drugs, coagulopathy and intra-abdominal tumors. In patients with polymyositis and dermatomyositis, acute abdomen is attributed to intestinal vasculitis causing ischemia, ulceration or perforation. Spontaneous retroperitoneal hemorrhage, however, has rarely been reported in patients with polymyositis. We report the case of a 65-year-old woman with newly diagnosed polymyositis and suspected thymoma who suffered from spontaneous retroperitoneal hemorrhage. She experienced two massive retroperitoneal hemorrhage episodes within 24 hours, which resulted in shock and required emergent angiographic embolization. There was no evidence of tumor, vasculitis or aneurysm from abdominal angiography and computed tomography.

  14. Language in individuals with left hemisphere tumors: Is spontaneous speech analysis comparable to formal testing?

    Science.gov (United States)

    Rofes, Adrià; Talacchi, Andrea; Santini, Barbara; Pinna, Giampietro; Nickels, Lyndsey; Bastiaanse, Roelien; Miceli, Gabriele

    2018-01-31

    The relationship between spontaneous speech and formal language testing in people with brain tumors (gliomas) has been rarely studied. In clinical practice, formal testing is typically used, while spontaneous speech is less often evaluated quantitatively. However, spontaneous speech is quicker to sample and may be less prone to test/retest effects, making it a potential candidate for assessing language impairments when there is restricted time or when the patient is unable to undertake prolonged testing. To assess whether quantitative spontaneous speech analysis and formal testing detect comparable language impairments in people with gliomas. Specifically, we addressed (a) whether both measures detected comparable language impairments in our patient sample; and (b) which language levels, assessment times, and spontaneous speech variables were more often impaired in this subject group. Five people with left perisylvian gliomas performed a spontaneous speech task and a formal language assessment. Tests were administered before surgery, within a week after surgery, and seven months after surgery. Performance on spontaneous speech was compared with that of 15 healthy speakers. Language impairments were detected more often with both measures than with either measure independently. Lexical-semantic impairments were more common than phonological and grammatical impairments, and performance was equally impaired across assessment time points. Incomplete sentences and phonological paraphasias were the most common error types. In our sample both spontaneous speech analysis and formal testing detected comparable language impairments. Currently, we suggest that formal testing remains overall the better option, except for cases in which there are restrictions on testing time or the patient is too tired to undergo formal testing. In these cases, spontaneous speech may provide a viable alternative, particularly if automated analysis of spontaneous speech becomes more readily

  15. Pulmonar collision tumor: Metastatic adenoid cystic carcinoma and lung adenocarcinoma

    OpenAIRE

    M. Blanco; E. García-Fontán; J. Ríos; J.E. Rivo; R. Fernández-Martín; M.A. Cañizares

    2012-01-01

    Summary: We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Resumo: Descreve...

  16. The relationship between tumor markers and pulmonary embolism in lung cancer.

    Science.gov (United States)

    Xiong, Wei; Zhao, Yunfeng; Xu, Mei; Guo, Jian; Pudasaini, Bigyan; Wu, Xueling; Liu, Jinming

    2017-06-20

    Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend tumor markers, TMs panel (OR5.98, P Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

  17. Phyllodes tumor of the breast with lung metastasis

    International Nuclear Information System (INIS)

    Arias Beaton, Ernesto; Oca Santiago, Pedro Montes de; Arias Beaton, Martha Beatriz

    2012-01-01

    The case report of a 63-year-old patient is described, who was admitted to 'Dr. Juan Bruno Zayas Alfonso' Teaching General Hospital of Santiago de Cuba due to persistent dry cough, little expectoration (sometimes yellowish), asthenia and loss of weight. On physical examination a tumor was palpated in the right breast, which was confirmed through sonography and mammogram. The results of the fine-needle biopsy were positive for neoplastic cells, consistent with carcinoma. Chest radiography and computerized axial tomography revealed the presence of lung metastatic images, reason why tumor excision with a safety margin of 2 cm was performed. The presence of phyllodes tumor was confirmed by means of the histopathologic study, so that it was necessary to indicate 3 cycles of chemotherapy (CISCYVADACT scheme), of which only two were administered as the old woman had an unfavorable course and she died 3 months later

  18. 4D Proton treatment planning strategy for mobile lung tumors

    International Nuclear Information System (INIS)

    Kang Yixiu; Zhang Xiaodong; Chang, Joe Y.; Wang He; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Balter, Peter A.; Liu, Helen; Zhu, X. Ronald; Mohan, Radhe; Dong Lei

    2007-01-01

    Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE R IGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE R IGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE R IGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors

  19. Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease.

    Science.gov (United States)

    Van Dyken, Steven J; Liang, Hong-Erh; Naikawadi, Ram P; Woodruff, Prescott G; Wolters, Paul J; Erle, David J; Locksley, Richard M

    2017-04-20

    The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. (Department of Biology, Indiana University-Purdue University, Indianapolis (United States))

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  1. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    International Nuclear Information System (INIS)

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W.

    1991-01-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication

  2. Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.

    Directory of Open Access Journals (Sweden)

    Scott J Goldman

    2011-03-01

    Full Text Available In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for

  3. Association between Congenital Lung Malformations and Lung Tumors in Children and Adults: A Systematic Review.

    Science.gov (United States)

    Casagrande, Arianna; Pederiva, Federica

    2016-11-01

    The appropriate management of asymptomatic congenital pulmonary malformations (CPMs) remains controversial. Prophylactic surgery is recommended to avoid the risk for development of pulmonary infections and to prevent the highly debated development of malignancy. However, the true risk for development of malignancy remains unknown. A systematic review analyzed all cases in which lung tumors associated with CPMs in both the pediatric and adult populations were described. A comprehensive literature search was carried out; it included all the cases in which an association between CPMs and malignant pulmonary lesions was reported. In all, 134 publications were eligible for inclusion. In 168 patients CPM was found associated with lung tumor. The diagnosis was made in 76 children at a mean age of 3.68 ± 3.4, whereas in the adult population (n = 92) it was made at a mean age of 44.62 ± 16.09. Cough was the most frequent presenting symptom both in children and in adults. Most of the patients underwent lobectomy. The tumor most often associated with CPM was pleuropulmonary bastoma in children (n = 31) and adenocarcinoma (n = 20) or bronchioloalveolar carcinoma (n = 20) in adults. The CPM most frequenty associated with tumors in children was congenital cystic adenomatoid malformation (n = 37), especially type 1 (n = 21), whereas in adults it was bronchogenic cyst (n = 25), followed by congenital cystic adenomatoid malformation (n = 21). CPMs should be followed up and never underestimated because they may conceal a tumor. Apparently, there is no age limit for malignant progression of CPMs and no limit of the interval between first detection of the CPM and appearance of the associated tumor. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  4. Assessment of tumors of the lung apex by imaging techniques

    International Nuclear Information System (INIS)

    Rueda, J.; Serrano, F.; Pain, M.I.; Rodriguez, F.

    1996-01-01

    The purpose of this study was to analyze the value of MR in the preoperative staging of tumors of the lung apex and detection of local invasion of adjacent structures to determine its influence on the therapeutic approach. We obtained plain X-ray images in two planes, as well as CT and Mr images, in 12 patients with Pan coast tumor in whom there was surgical (n=8) or clinical (n=4) evidence of invasion. The objective was to assess local infiltration of brain stem and chest wall soft tissue, enveloping of the subclavian artery, substantial involvement of the brachial plexus and destruction of the vertebral body. In our series, MR was superior to the other imaging techniques in predicting the involvement of the structures surrounding the tumor. In conclusion, MR should be performed in a patient diagnosed by plain radiography as having an apical tumors to assess local tumor extension, while CT should be done to detect mediastinal lymph node involvement and distant metastases. 19 refs

  5. On the influence of ultraviolet radiation on spontaneous tumors in NMRI mice

    International Nuclear Information System (INIS)

    Koenigsmann, G.; Kinkel, H.J.; Bocionek, P.; Wolff, F.

    1981-01-01

    During a period of 12 and 15 months respectively, female NMRI mice were irradiated twelve hours per day with specific parts of the ultraviolet spectrum (three groups, each comprising 100 animals: non-irradiated control group, animals irradiated with B units, animals irradiated with A/B units). No considerable influence of the chronic exposure to ultraviolet radiation could be demonstrated with regard to the development of the body weight and the hematologic condition. Group B had the same rate of spontaneous tumors of the respiratory tract as the control group; this rate was higher in group A/B. As to the development of spontaneous tumors in the lymphatic tissues, there seems to be a dependence on radiation: the animals of group B presented a slightly higher, those of group A/B a higher development than the animals of the nonirradiated control group. It cannot be definitely clarified yet to what extent this increased tumor rate was additionally induced by the higher environmental temperature or other influences involved by experiment. Harding-Passey melanomas were inoculated in NMRI mice and, 48 hours later, they were exposed to defined emission spectra within the natural ultraviolet spectrum. The exposed animals showed a slower growth of the transplanted tumors than the non-exposed animals, and especially the animals exposed to UVB radiation had a longer survival time. This chronic irradiation test was carried out in order to examine the influence of defined emission spectra on autochthonous tumors in NMRI mice and on their spontaneous tumor rate and blood count. (orig.) [de

  6. Pulmonar collision tumor: metastatic adenoid cystic carcinoma and lung adenocarcinoma.

    Science.gov (United States)

    Blanco, M; García-Fontán, E; Ríos, J; Rivo, J E; Fernández-Martín, R; Cañizares, M A

    2012-01-01

    We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  7. Tumor specific lung cancer diagnostics with multiplexed FRET immunoassays

    Science.gov (United States)

    Geißler, D.; Hill, D.; Löhmannsröben, H.-G.; Thomas, E.; Lavigne, A.; Darbouret, B.; Bois, E.; Charbonnière, L. J.; Ziessel, R. F.; Hildebrandt, N.

    2010-02-01

    An optical multiplexed homogeneous (liquid phase) immunoassay based on FRET from a terbium complex to eight different fluorescent dyes is presented. We achieved highly sensitive parallel detection of four different lung cancer specific tumor markers (CEA, NSE, SCC and CYFRA21-1) within a single assay and show a proof-of-principle for 5- fold multiplexing. The method is well suited for fast and low-cost miniaturized point-of-care testing as well as for highthroughput screening in a broad range of in-vitro diagnostic applications.

  8. In vivo BNCT in experimental and spontaneous tumors at RA-1 reactor

    International Nuclear Information System (INIS)

    Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Schwint, Amanda E.; Nigg, David W.

    2003-01-01

    Within the search for new applications of Boron Neutron Capture Therapy (BNCT) and the basic research oriented towards the study of BNCT radiobiology to optimize its therapeutic gain, we previously proposed and validated the hamster cheek pouch oral cancer model and showed, for the first time, the success of BNCT to treat oral cancer in an experimental model. The staff of the Ra-1 Reactor (Constituyentes Atomic Center) adapted the thermal beam and physical set-up to perform in vivo BNCT of superficial tumors in small animals. We preformed a preliminary characterization of the thermal beam, performed beam only irradiation of normal and tumor bearing hamsters and in vivo BNCT of experimental oral squamous cell carcinomas in hamsters mediated by boron phenylalanine (BPA) and GB-10 (Na 2 10 B 10 H 10 ). Having demonstrated the absence of radio toxic effects in healthy tissue and a therapeutic effect of in vivo BNCT in hamster cheek pouch tumors employing the Ra-1 thermal beam, we performed a feasibility study of the treatment by BNCT of 3 terminal cases of spontaneous head and neck squamous cell carcinoma in cats following the corresponding biodistribution studies. This was the first treatment of spontaneous tumors by BNCT in our country and the first treatment by BNCT in cats worldwide. This preclinical study in terminal cases showed significant tumor control by BNCT with no damage to normal tissue. (author)

  9. Expression of the p16{sup INK4a} tumor suppressor gene in rodent lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Swafford, D.S.; Tesfaigzi, J.; Belinsky, S.A.

    1995-12-01

    Aberrations on the short arm of chromosome 9 are among the earliest genetic changes in human cancer. p16{sup INK4a} is a candidate tumor suppressor gene that lies within human 9p21, a chromosome region associated with frequent loss of heterozygosity in human lung tumors. The p16{sup INK4a} protein functions as an inhibitor of cyclin D{sub 1}-dependent kinases that phosphorylate the retinoblastoma (Rb) tumor suppressor gene product enabling cell-cycle progression. Thus, overexpression of cyclin D{sub 1}, mutation of cyclin-dependent kinase genes, or loss of p16{sup INK4a} function, can all result in functional inactivation of Rb. Inactivation of Rb by mutation or deletion can result in an increase in p16{sup INK4a} transcription, suggesting that an increased p16{sup INK4a} expression in a tumor cell signals dysfunction of the pathway. The p16{sup (INK4a)} gene, unlike some tumor suppressor genes, is rarely inactivated by mutation. Instead, the expression of this gene is suppressed in some human cancers by hypermethylation of the CpG island within the first exon or by homozygous deletion: 686. Chromosome losses have been observed at 9p21 syntenic loci in tumors of the mouse and rat, two species often used as animal models for pulmonary carcinogenesis. Expression of p16{sup INK4a} is lost in some mouse tumor cell lines, often due to homozygous deletion. These observations indicate that p16{sup INK4a} dysfunction may play a role in the development of neoplasia in rodents as well as humans. The purpose of the current investigation was to define the extent to which p16{sup INK4a} dysfunction contributes to the development of rodent lung tumors and to determine the mechanism of inactivation of the gene. There is no evidence to suggest a loss of function of the p16{sup INK4a} tumor suppressor gene in these primary murine lung tumors by mutation, deletion, or methylation.

  10. Promoter methylation is not associated with FLCN irregulation in lung cyst lesions of primary spontaneous pneumothorax.

    Science.gov (United States)

    Ding, Yibing; Zou, Wei; Zhu, Chengchu; Min, Haiyan; Ma, Dehua; Chen, Baofu; Ye, Minhua; Pan, Yanqing; Cao, Lei; Wan, Yueming; Zhu, Qiuxiang; Xia, Haizhen; Zhang, Wenwen; Feng, Ying; Gao, Qian; Yi, Long

    2015-11-01

    Germline mutations in FLCN are responsible for ~10% of patients with primary spontaneous pneumothorax (PSP), characterized by multiple lung cysts in the middle/lower lobes and recurrent pneumothorax. These clinical features are also observed in a substantial portion of patients with sporadic PSP exhibiting no FLCN coding mutations. To assess the potential underlying mechanisms, 71 patients with PSP were selected, including 69 sporadic and 2 familial cases, who bared FLCN mutation‑like lung cysts, however, harbored no FLCN protein‑altering mutations. Notably, in a significant proportion of the patients, FLCN irregulation was observed at the transcript and protein levels. Genetic analyses of the cis‑regulatory region of FLCN were performed by sequencing and multiplex ligation‑dependent probe amplification assay. No inheritable DNA defect was detected, with the exception of a heterozygous deletion spanning the FLCN promoter, which was identified in a family with PSP. This mutation caused a reduction in the expression of FLCN in the lung cysts. Pedigree analysis demonstrated that haploinsufficiency of FLCN was pathogenic. To determine whether epigenetic mechanisms may be involved in the irregulation of FLCN, the promoter methylation status was measured in the remainder of the patients. No evidence of FLCN promoter methylation was demonstrated. The present study suggested that FLCN irregulation in lung cysts of PSP is not associated with promoter methylation.

  11. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer.

    Science.gov (United States)

    Grunnet, M; Sorensen, J B

    2012-05-01

    The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA serum level as a prognostic marker in NSCLC was investigated in 23 studies and the use of CEA plasma level in two. In 18 (17 serum, 1 plasma) of these studies CEA was found to be a useful prognostic marker for either OS, recurrence after surgery or/and progression free survival (PFS) in NSCLC patients. Interestingly, an overweight of low stage (stage I-II) disease and adenocarcinoma (AC) patients were observed in this group. The remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with squamous carcinoma (SQ). One study found evidence for that a tumor marker index (TMI), based on preoperative CEA and CYFRA21-1 serum levels, is useful as a prognostic marker for OS in NSCLC. Six studies evaluated the use of CEA as a predictive marker for risk of recurrence and risk of death in NSCLC patients. Four of these studies found, that CEA was useful as a predictive marker for risk of recurrence and risk of death measured over time. No studies found CEA levels useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of CEA measured in tumor tissue in

  12. Tumor-Induced CD8+ T-Cell Dysfunction in Lung Cancer Patients

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    Heriberto Prado-Garcia

    2012-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating lymphocytes (TILs and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer.

  13. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

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    David Fecher

    Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

  14. Quantitative study on lung volume and lung perfusion using SPECT and CT in thoracal tumors

    International Nuclear Information System (INIS)

    Beyer-Enke, S.A.; Goerich, J.; Strauss, L.G.

    1988-01-01

    22 patients with space occupying lesions in the thoracal region were investigated by computer tomography and by perfusion scintigraphy using SPECT. In order to evaluate the CT images quantitatively, the lung volume was determined using approximation method and compared with the perfusion in the SPECT study. For this, anatomically equivalent transaxial SPECT slices had been coordinated to the CT slices. Between the determined lung volumes and the activity in the ocrresponding layers, a statistically significant correlation was found. It could be shown that the stronger perfusion, frequently observed at the right side of the healthy lung, may be explained by an higher volume of the right pulmonary lobe. Whereas in benign displacing processes the relation activity to volume was similar to the one of the healthy lung, a strongly reduced perfusion together with inconspicuous lung volumes became apparent with malignant tumors. In addition to the great morphological evidence of CT and SPECT studies, additional informations regarding the dignity of displacing processes may be derived from the quantitative evaluation of both methods. (orig.) [de

  15. Pulmonar collision tumor: Metastatic adenoid cystic carcinoma and lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    M. Blanco

    2012-01-01

    Full Text Available Summary: We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Resumo: Descrevemos um caso único de tumor de colisão constituído por um adenocarcinoma de pulmão e uma metástase dum carcinoma adenóide cístico em um homem de 56 anos de idade. Ao doente foi diagnosticado um nódulo pulmonar 11 anos após o tratamento de um carcinoma adenóide cístico do seio maxilar direito. O carcinoma de pulmão de não pequenas células foi observado no momento da realização de uma biópsia transbrônquica. O outro componente do nódulo foi diagnosticado depois do exame histológico do material ressecado. Keywords: Bronchogenic carcinoma, Collision tumor, Adenoid cystic carcinoma, Palavras-chave: Carcinoma broncogénico, Tumor de colisão, Carcinoma adenóide cístico

  16. Tumor-size-based morphological features of metastatic lymph node tumors from primary lung adenocarcinoma.

    Science.gov (United States)

    Yamada, Eiji; Ishii, Genichiro; Aramaki, Nao; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Kojima, Motohiro; Nagai, Kanji; Ochiai, Atsushi

    2014-12-01

    Most primary lung adenocarcinomas show histological diversity, however, histological diversity in the metastatic lymph node tumors (LNT) is not well defined. The aim of this study was to explore the histological characteristics of the metastatic LNT based on their sizes. We analyzed 163 primary tumors and 509 metastatic LNTs. When the primary tumor showed papillary-predominant subtype, the most frequent histological subtype in the metastatic LNT that were ≤2 mm in diameter was solid subtype (49%), followed by papillary subtype (35%); on the other hand, in the metastatic LNT measuring >2 mm in size, the frequency of tumors showing papillary-predominant subtype increased significantly to 52% (P = 0.04). When the primary tumor showed acinar-predominant subtype, the most predominant subtype in the ≤2 mm metastatic LN tumors was acinar subtype (55%), followed by solid subtype (40%), with the frequency of acinar subtype increasing significantly to 76% in the metastatic LNT that were >2 mm in diameter (P = 0.04). These results indicate that solid subtype is the characteristic histological subtype in the early phase of the LN metastatic process, and that as the metastatic LNT grow larger, they develop morphological features resembling those in the primary tumor. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  17. Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-08-15

    A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

  18. Detection of lung tumor movement in real-time tumor-tracking radiotherapy

    International Nuclear Information System (INIS)

    Shimizu, Shinichi; Shirato, Hiroki; Ogura, Shigeaki; Akita-Dosaka, Hirotoshi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Nishimura, Masaji; Miyasaka, Kazuo

    2001-01-01

    Purpose: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. Methods and Materials: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined 'permitted dislocation'. The value was set at ±1 to ±3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. Results: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p=0.007), y (p=0.025), and z (p=0.002) coordinates, respectively. Conclusion: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the 'permitted dislocation' zone from the planned position

  19. Video-Assisted Thoracoscopic Surgery in Patients With Clinically Resectable Lung Tumors

    Directory of Open Access Journals (Sweden)

    H. Sakai

    1996-01-01

    Full Text Available To investigate the feasibility of thoracoscopic resection, a pilot study was performed in patients with clinically resectable lung tumors. In 40 patients, Video-assisted thoracic surgery (VATS was performed because of suspicion of malignancy. There were 29 men and 11 women with a median age of 54.8 years (range 18 to 78. Preoperative indications were suspected lung cancer and tumor in 27 patients, assessment of tumor resectability in 7 patients, and probability of metastatic tumors in 6 patients. The final diagnoses in the 27 patients with suspected lung cancer were 12 primary lung cancers, 6 lung metastases, and 9 benign lesions. The success rates for VATS (no conversion to thoracotomy were 1 of 12 (8.3% for resectable stage I lung cancer, 8 of 12 (66.7% for metastatic tumors, and 9 of 9 (100% for benign tumors. With VATS, 6 of 7 patients (85.7%, possible stage III non-small cell lung cancer, an explorative thoracotomy with was avoided, significantly reducing morbidity. The reasons for conversion to thoracotomy were 1 oncological (N2 lymph node dissection and prevention of tumor spillage and 2 technical (inability to locate the nodule, central localization, no anatomical fissure, or poor lung function requiring full lung ventilation. The ultimate diagnoses were 19 lung cancers, 12 metastatic lung tumors, and 9 benign lung tumors. Our data show the limitations of VATS for malignant tumors in general use. These findings, together with the fact that experience in performing thoracoscopic procedures demonstrates a learning curve, may limit the use of thoracoscopic resection as a routine surgical procedure, especially when strict oncological rules are respected.

  20. Photodynamic therapy on spontaneous tumors of dogs and cats: a ten-year study

    Science.gov (United States)

    Fonda, Diego

    1992-06-01

    Since 1981, more than fifty spontaneous tumors of dogs and cats were treated by photodynamic therapy with hematoporphyrins in the surgery department of the University of Milan. Therapeutic results proved to be successful and promising in certain forms of cancer and will be compared in the future with the effectiveness of other photosensitizer drugs like phatolocyanines derivatives. Applied hematoporphyrins phototherapy methods included: (1) injection of hematoporphyrins derivative (HpD) and irradiation with laser light at 631 nanometers, using a Rhodamine B dye laser; (2) injection of the active component of hematoporphyrin derivative (DHE) and irradiation with a Rhodamine B dye laser; and (3) injection of DHE and irradiation with laser light at 628 nanometers using a gold vapor laser. More frequently treated tumor sites were oral and nasal cavities. Other localizations were mucous membranes of the glans and stomach. Nineteen histological types were diagnosed in treated tumors.

  1. SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation

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    Wang, Jia-lei [Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Lu, Fan-zhen [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Shen, Xiao-Yong, E-mail: shengxiaoyong_sh@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Wu, Yun, E-mail: WuYun_hd@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Zhao, Li-ting [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China)

    2014-12-12

    Highlights: • SAMHD1 expression level is down regulated in lung adenocarcinoma. • The promoter of SAMHD1 is methylated in lung adenocarcinoma. • Over expression of SAMHD1 inhibits the proliferation of lung cancer cells. - Abstract: The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells.

  2. Three-dimensional ultrashort echo time MRI and Short T2 images generated from subtraction for determination of tumor burden in lung cancer: Preclinical investigation in transgenic mice.

    Science.gov (United States)

    Müller, Andreas; Jagoda, Philippe; Fries, Peter; Gräber, Stefan; Bals, Robert; Buecker, Arno; Jungnickel, Christopher; Beisswenger, Christoph

    2018-02-01

    To investigate the potential of 3D ultrashort echo time MRI and short T 2 images generated by subtraction for determination of total tumor burden in lung cancer. As an animal model of spontaneously developing non-small cell lung cancer, the K-rasLA1 transgenic mouse was used. Three-dimensional MR imaging was performed with radial k-space acquisition and echo times of 20 µs and 1 ms. For investigation of the short T 2 component in the recorded signal, subtraction images were generated from these data sets and used for consensus identification of tumors. Next, manual segmentation was performed on all MR images by two independent investigators. MRI data were compared with the results from histologic investigations and among the investigators. Tumor number and total tumor burden from imaging experiments correlated strongly with the results of histologic investigations. Intra- and interuser comparison showed highest correlations between the individual measurements for ultra-short TE MRI. Three-dimensional MRI protocols facilitate accurate tumor identification in mice harboring lung tumors. Ultrashort TE MRI is the superior imaging strategy when investigating lung tumors of miscellaneous size with 3D MR imaging strategies. Magn Reson Med 79:1052-1060, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  3. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    International Nuclear Information System (INIS)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

    2010-01-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  4. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  5. Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

    International Nuclear Information System (INIS)

    Yu, Lunyin; Hales, Charles A

    2011-01-01

    Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

  6. Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Jason M. Fritz

    2014-11-01

    Full Text Available Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2 had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression.

  7. Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

    International Nuclear Information System (INIS)

    Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

    1988-01-01

    Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

  8. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model.

    Science.gov (United States)

    MacDiarmid, Jennifer A; Langova, Veronika; Bailey, Dale; Pattison, Scott T; Pattison, Stacey L; Christensen, Neil; Armstrong, Luke R; Brahmbhatt, Vatsala N; Smolarczyk, Katarzyna; Harrison, Matthew T; Costa, Marylia; Mugridge, Nancy B; Sedliarou, Ilya; Grimes, Nicholas A; Kiss, Debra L; Stillman, Bruce; Hann, Christine L; Gallia, Gary L; Graham, Robert M; Brahmbhatt, Himanshu

    2016-01-01

    Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR

  9. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model.

    Directory of Open Access Journals (Sweden)

    Jennifer A MacDiarmid

    Full Text Available Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers.EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT and magnetic resonance imaging (MRI. Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973. No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs.Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of

  10. Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Binkley, Michael S. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Shrager, Joseph B. [Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Leung, Ann N. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Popat, Rita [Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California (United States); Trakul, Nicholas [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Atwood, Todd F.; Chaudhuri, Aadel [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Maxim, Peter G. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2014-09-01

    Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across

  11. Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

    International Nuclear Information System (INIS)

    Yang, Jie; Li, Jun-Wen; Wang, Lu; Chen, Zhaoli; Shen, Zhi-Qiang; Jin, Min; Wang, Xin-Wei; Zheng, Yufei; Qiu, Zhi-Gang; Wang, Jing-feng

    2008-01-01

    Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies. In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking. Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed. We conclude that VE might prevent lung tumor induced by smoking in Swiss mice

  12. Spontaneous chylothorax complicating small cell lung cancer – Review of aetiology and diagnosis

    Directory of Open Access Journals (Sweden)

    S. Hanina

    2015-01-01

    Full Text Available We report the first case of spontaneous chylothorax complicating small cell lung cancer. A 52 year old female presented with exertional dyspnoea, left-sided chest and neck pain, and dysphagia. The chest X-ray on admission revealed a large left-sided pleural effusion. A subsequent CT chest showed a large anterior mediastinal mass with a left brachiocephalic and jugular vein thrombosis. The patient underwent medical thoracoscopy with chest drain insertion, which drained pleural fluid high in triglycerides, consistent with a chylothorax. Due to its uncommon nature, the management of chylothorax is not well defined. Alongside the case report, we provide a review of aetiology, mechanism and diagnosis with a brief summary of treatment options.

  13. Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM...derive a prognostic classifier. 15. SUBJECT TERMS NSCLC; tumor evolution ; whole exome sequencing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  14. Acute and late reactions following boron neutron capture epithermal-neutron therapy in dogs with spontaneous brain tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; DeHaan, C.E.; Kraft, S.L.; Moore, M.P.; Wendling, L.R.; Dorn, R.V. III.

    1992-01-01

    Dogs have a relatively high incidence of primary tumors of the central nervous system and have proven to be good models for new therapeutic investigation. The pharmacokinetics of borocaptate sodium have been well documented in the dog. Preliminary investigations of the normal tissue tolerance and was designed to ensure a therapeutic margin was present for the dogs with spontaneous tumors; i.e., a measurable effect could be had on the tumor at doses considered safe for the normal tissues

  15. Diagnosis significance of combined determination of 3 tumor markers in serum in patients with lung cancer

    International Nuclear Information System (INIS)

    Zuo Zhitong; Ling Chunhua; Zheng Shiying; Liu Hao

    2005-01-01

    Objective: To investigate the value of 3 tumor markers in serum for diagnosis in patients with lung cancer. Methods: The level of TSGF, CYFRA21-1 and NSE in serum was measured in patients with lung cancer and benign lung disease by using Chromatometry of Biochemistry and Chemiluminoimmunoassay methods respectively. Results: The level of all 3 tumor markers measured in serum was much higher in lung cancer group than that in benign lung disease group (P<0.01 or P<0.05). The sensibitity and specificity of TSGF were 84.8% and 86.1%. CYFRA21-1 and NSE increased in different degrees among the patients classified in accordence with various pathological categories. Conclusions: The measurement of the tumor markers in serum contributes to the diagnosis, pathological classification evaluation of lung cancer. TSGF is a satisfactory screening marker of health examination. (authors)

  16. Detection of five tumor markers in lung cancer by trypsin digestion of sputum method

    International Nuclear Information System (INIS)

    Lin Min; Nong Tianlei; Liu Daying

    2011-01-01

    To explore the detection of five tumor markers by trypsin digestion of sputum in the diagnosis of lung cancer, the samples of sputum in patients with lung cancer and benign lung disease were digested by trypsin and used to measure five tumor markers. The results showed that the sputum were well digested by 6% trypsin at pH8 and no affect on the determination of tumor markers. The CEA, CA125, CA153, CA211 and NSE levels in lung cancer group were significantly higher than that of in benign group (P<0.05). The sputum CEA and CA125 levels were significantly higher than that of the serum levels (P<0.05). The detection of sputum CEA, CA125, CA153, CA211 and NSE levels have clinical value in the diagnosis of lung cancer. When combined with other diagnostic methods,it might be helpful for further diagnosis in non confirmed lung cancer patients. (authors)

  17. Prognostic value of PET/CT in lung cancer. Study of survival and tumor metabolic characterization

    International Nuclear Information System (INIS)

    Ladron de Guevara, David; Fuentes Anibal; Farina, Ciro; Corral, Camilo; Pefaur, Raul

    2013-01-01

    PET/CT (Positron emission tomography/computed tomography) is a hybrid image modality widely used in oncology, for staging, therapy evaluation or follow up. Aim: To evaluate the prognostic value of PET/CT in lung cancer. Material and Methods: Retrospective review of PET/CT records, selecting 51 patients with a lung malignancy, mass or nodule referred for PET/CT between December 2008 and December 2010. All had pathological confirmation of malignancy and had not been treated previously. Age, gender, body mass index, radiological features of lung tumor and metastases, and lung tumor 18 F-fluoro-2-deoxy-d-glucose uptake using the SUV (Standardized uptake value) index were recorded. Survival was analyzed using Kaplan-Meier curves and a Cox proportional regression analysis. Results: Pathology confirmed the presence of lung cancer in 47 patients aged 30 to 88 years. Four patients (7.8%) had other type of tumors such as carcinoid or lymphoma. Fifty percent of lung cancer patients died during a mean observation lapse of 18 months (range: 2-34 months). Patients with metastases, local lymph node involvement, a lung tumor size ≥ 3 cm and high tumor uptake (SUVmax > 6) had significantly lower survival. Occurrence of metastases was the only independent prognostic factor in the Cox regression. A lung lesion with a SUVmax ≥ 12 was always associated to hilar/mediastinal lymph node involvement. Conclusions: PET/CT imaging gives important prognostic information in lung cancer patients

  18. Density overwrites of internal tumor volumes in intensity modulated proton therapy plans for mobile lung tumors

    Science.gov (United States)

    Botas, Pablo; Grassberger, Clemens; Sharp, Gregory; Paganetti, Harald

    2018-02-01

    The purpose of this study was to investigate internal tumor volume density overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan degradation of mobile lung tumors. Four planning paradigms were compared for nine lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical target volume (ICTV) structures were defined encompassing their respective volumes in every 4DCT phase. The paradigms use different planning CT (pCT) created from the average intensity projection (AIP) of the 4DCT, overwriting the density within the IGTV to account for movement. The density overwrites were: (a) constant filling with 100 HU (C100) or (b) 50 HU (C50), (c) maximum intensity projection (MIP) across phases, and (d) water equivalent path length (WEPL) consideration from beam’s-eye-view. Plans were created optimizing dose-influence matrices calculated with fast GPU Monte Carlo (MC) simulations in each pCT. Plans were evaluated with MC on the 4DCTs using a model of the beam delivery time structure. Dose accumulation was performed using deformable image registration. Interplay effect was addressed applying 10 times rescanning. Significantly less DVH metrics degradation occurred when using MIP and WEPL approaches. Target coverage (D99≥slant 70 Gy(RBE)) was fulfilled in most cases with MIP and WEPL (D{{99}WEPL}=69.2+/- 4.0 Gy (RBE)), keeping dose heterogeneity low (D5-D{{95}WEPL}=3.9+/- 2.0 Gy(RBE)). The mean lung dose was kept lowest by the WEPL strategy, as well as the maximum dose to organs at risk (OARs). The impact on dose levels in the heart, spinal cord and esophagus were patient specific. Overall, the WEPL strategy gives the best performance and should be preferred when using a 3D static geometry for lung cancer IMPT treatment planning. Newly available fast MC methods make it possible to handle long simulations based on 4D data sets to perform studies with high accuracy and efficiency, even prior to individual treatment planning.

  19. Radiographically determined growth kinetics of primary lung tumors in the dog

    International Nuclear Information System (INIS)

    Perry, R.E.; Weller, R.E.; Buschbom, R.L.; Dagle, G.E.; Park, J.F.

    1989-10-01

    Tumor growth rate patterns especially tumor doubling time (TDT), have been extensively evaluated in man. Studies involving the determination of TDT in humans are limited, however, by the number of cases, time consistent radiographic tumor measurements, and inability to perform experimental procedures. In animals similar constraints do not exist. Lifespan animal models lend themselves well to tumor growth pattern analysis. Experimental studies have been designed to evaluate both the biological effects and growth patterns of induced and spontaneous tumors. The purpose of this study was to calculate the tumor volume doubling times (TCDT) for radiation-induced and spontaneous primary pulmonary neoplasms in dogs to see if differences existed due to etiology, sex or histologic cell type, and to determine if the time of tumor onset could be extrapolated from the TVDT. 3 refs

  20. Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

    International Nuclear Information System (INIS)

    Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori; Narabayashi, Masaru; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    2009-01-01

    Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using one display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.

  1. Spontaneous breathing or mechanical ventilation alters lung compliance and tissue association of exogenous surfactant in preterm newborn rabbits.

    Science.gov (United States)

    Bohlin, Kajsa; Bouhafs, Rabea K L; Jarstrand, Connie; Curstedt, Tore; Blennow, Mats; Robertson, Bengt

    2005-05-01

    In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant (14C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 +/- 10% (mean +/- SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml x cm H2O(-1) x kg(-1), respectively; p mechanically ventilated animals (p mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation.

  2. A comparison of tumor motion characteristics between early stage and locally advanced stage lung cancers

    International Nuclear Information System (INIS)

    Yu, Z. Henry; Lin, Steven H.; Balter, Peter; Zhang Lifei; Dong Lei

    2012-01-01

    Purpose: With the increasing use of conformal radiation therapy methods for non-small cell lung cancer (NSCLC), it is necessary to accurately determine respiratory-induced tumor motion. The purpose of this study is to analyze and compare the motion characteristics of early and locally advanced stage NSCLC tumors in a large population and correlate tumor motion with position, volume, and diaphragm motion. Methods and materials: A total of 191 (94 early stage, 97 locally advanced) non-small cell lung tumors were analyzed for this study. Each patient received a four-dimensional CT scan prior to receiving radiation treatment. A soft-tissue-based rigid registration algorithm was used to track the tumor motion. Tumor volumes were determined based on the gross tumor volume delineated by physicians in the end of expiration phase. Tumor motion characteristics were correlated with their standardized tumor locations, lobe location, and clinical staging. Diaphragm motion was calculated by subtracting the diaphragm location between the expiration and the inspiration phases. Results: Median, max, and 95th percentile of tumor motion for early stage tumors were 5.9 mm, 31.0 mm, and 20.0 mm, which were 1.2 mm, 12 mm, and 7 mm more than those in locally advanced NSCLC, respectively. The range of motion at 95th percentile is more than 50% larger in early stage lung cancer group than in the locally advanced lung cancer group. Early stage tumors in the lower lobe showed the largest motion with a median motion of 9.2 mm, while upper/mid-lobe tumors exhibited a median motion of 3.3 mm. Tumor volumes were not correlated with motion. Conclusion: The range of tumor motion differs depending on tumor location and staging of NSCLC. Early stage tumors are more mobile than locally advanced stage NSCLC. These factors should be considered for general motion management strategies when 4D simulation is not performed on individual basis.

  3. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    International Nuclear Information System (INIS)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

    2014-01-01

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

  4. The role of neutrophil myeloperoxidase in models of lung tumor development.

    Science.gov (United States)

    Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  5. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  6. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Directory of Open Access Journals (Sweden)

    Amy L. Rymaszewski

    2014-05-01

    Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  7. Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue

    Energy Technology Data Exchange (ETDEWEB)

    Waelti, Stephan L.; Garel, Laurent; Rypens, Francoise; Dubois, Josee [University of Montreal, Department of Medical Imaging, Sainte-Justine Hospital, Quebec (Canada); Dal Soglio, Dorothee [University of Montreal, Department of Pathology, Sainte-Justine Hospital, Quebec (Canada); Messerli, Michael [University Hospital Zurich, University of Zurich, Department of Nuclear Medicine, Zurich (Switzerland)

    2017-12-15

    The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10 years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible. (orig.)

  8. Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue

    International Nuclear Information System (INIS)

    Waelti, Stephan L.; Garel, Laurent; Rypens, Francoise; Dubois, Josee; Dal Soglio, Dorothee; Messerli, Michael

    2017-01-01

    The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10 years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible. (orig.)

  9. Audiovisual Biofeedback Improves Cine–Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Danny [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Greer, Peter B. [School of Mathematical and Physical Sciences, The University of Newcastle, Newcastle, NSW (Australia); Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Ludbrook, Joanna; Arm, Jameen; Hunter, Perry [Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Pollock, Sean; Makhija, Kuldeep; O' brien, Ricky T. [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Kim, Taeho [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Keall, Paul, E-mail: paul.keall@sydney.edu.au [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia)

    2016-03-01

    Purpose: To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients. Methods and Materials: Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio. Results: Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001). Conclusions: These results demonstrated that AV biofeedback significantly improved intra- and interfraction lung tumor motion consistency for lung cancer patients. These results demonstrate that AV biofeedback can facilitate consistent tumor motion, which is advantageous toward achieving more accurate medical imaging and radiation therapy procedures.

  10. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  11. Imaging Matrix Metalloproteases in Spontaneous Colon Tumors: Validation by Correlation with Histopathology.

    Science.gov (United States)

    Hensley, Harvey; Cooper, Harry S; Chang, Wen-Chi L; Clapper, Margie L

    2017-01-01

    The use of fluorescent probes in conjunction with white-light colonoscopy is a promising strategy for improving the detection of precancerous colorectal lesions, in particular flat (sessile) lesions that do not protrude into the lumen of the colon. We describe a method for determining the sensitivity and specificity of an enzymatically activated near-infrared probe (MMPSense680) for the detection of colon lesions in a mouse model (APC +/Min-FCCC ) of spontaneous colorectal cancer. Fluorescence intensity correlates directly with the activity of matrix metalloproteinases (MMPs). Overexpression of MMPs is an early event in the development of colorectal lesions. Although the probe employed serves as a reporter of the activity of MMPs, our method can be applied to any fluorescent probe that targets an early molecular event in the development of colorectal tumors.

  12. Analytical dosimetry for spontaneous tumor dogs receiving boron neutron capture therapy

    International Nuclear Information System (INIS)

    Wheeler, F.J.; Atkinson, C.A.; Gavin, P.R.

    1992-01-01

    The dog irradiation project of the Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program is administered by Washington State University (WSU) with analytical and physical dosimetry provided by the Idaho National Engineering Laboratory (INEL). One subtask of this project includes BNCT safety studies for dogs with spontaneously-occurring brain tumors. The boron compound (Na 2 B 12 H 11 SH or BSH) was administered and single irradiations performed using the epithermal-neutron beam at the Brookhaven Medical Research Reactor (BMRR). The main goal of the study was not to provide therapy, but to determine tumorcidal effect while administering a subtolerance dose to healthy tissue. Irradiation times were based on delivery of 19 Gy peak physical dose to the blood

  13. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer.

    OpenAIRE

    Faget, Julien; Groeneveld, Svenja; Boivin, Gael; Sankar, Martial; Zangger, Nadine; Garcia, Miguel; Guex, Nicolas; Zlobec, Inti; Steiner, Loïc; Piersigilli, Alessandra; Xenarios, Ioannis; Meylan, Etienne

    2017-01-01

    Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung c...

  14. Advances in the study of serum tumor markers of lung cancer

    OpenAIRE

    Wenjie Qi; Xuechang Li; Jingbo Kang

    2014-01-01

    Lung cancer is among the most prevalently occurring carcinomas worldwide, and reducing lung cancer mortality depends on early detection, diagnosis, and treatment. Given the rapid development of molecular biology and modern techniques for diagnosis and treatment, the study of serum tumor markers has gained extensive application in early diagnosis, treatment effect monitoring, and prognosis evaluation. Serum tumor markers possess the advantages of easy detection, noninvasive operation, and cost...

  15. Gene expression profiles of progestin-induced canine mammary hyperplasia and spontaneous mammary tumors.

    Science.gov (United States)

    Rao, N A S; van Wolferen, M E; Gracanin, A; Bhatti, S F M; Krol, M; Holstege, F C; Mol, J A

    2009-05-01

    Spontaneous mammary tumors are the most prevalent type of neoplasms in women as well as in female dogs. Although ovarian hormones estrogen and progesterone are known to play a key role in mammary tumorigenesis, conflicting reports have been obtained from in vivo and in vitro studies concerning the role of especially progesterone in mammary tumorigenesis. Prolonged exposure to high concentrations of progesterone during the unusually long luteal phase of the estrous cycle is suspected to be the key event in canine mammary tumorigenesis. Accordingly, previous studies have shown the development of mammary hyperplasia in dogs upon prolonged progestin administration. In this study, a dog-specific cDNA microarray was used to identify oncogenic determinants in progestin-induced canine hyperplasia (CMH) and spontaneous mammary tumors (CMC) by comparing expression profiles to those obtained from mammary glands of healthy dogs. The CMH profile showed elevated expression of genes involved in cell proliferation such as PCNA, NPY, RAN and also alterations in expression of transcription factors and cell adhesion molecules. Whereas in CMC, major alterations to the expression of genes involved in cell motility, cytoskeletal organization and extra cellular matrix production was evident besides differential expression of cell proliferation inducing genes. The overall gene expression profile of CMH was related to cell proliferation where as that of CMC was associated with both cell proliferation as well as neoplastic transformation. In conclusion, our findings support a strong cell proliferation inducing potential of progestins in the canine mammary gland. Moreover, deregulated genes identified in CMC are potentially involved in their malignant and may serve as prospective therapeutic targets.

  16. Flow cytometric applications of tumor biology: prospects and pitfalls. [Applications in study of spontaneous dog tumors and in drug and radiation effects on cultured V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.; Johnson, T.S.; Tokita, N.; Gillette, E.L.

    1979-01-01

    A brief review of cytometry instrumentation and its potential applications in tumor biology is presented using our recent data. Age-distribution measurements of cells from spontaneous dog tumors and cultured cells after exposure to x rays, alpha particles, or adriamycin are shown. The data show that DNA fluorescence measurements have application in the study of cell kinetics after either radiation or drug treatment. Extensive and careful experimentation is needed to utilize the sophisticated developments in flow cytometry instrumentation.

  17. Audiovisual biofeedback guided breath-hold improves lung tumor position reproducibility and volume consistency

    Directory of Open Access Journals (Sweden)

    Danny Lee, PhD

    2017-07-01

    Conclusions: This study demonstrated that audiovisual biofeedback can be used to improve the reproducibility and consistency of breath-hold lung tumor position and volume, respectively. These results may provide a pathway to achieve more accurate lung cancer radiation treatment in addition to improving various medical imaging and treatments by using breath-hold procedures.

  18. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  19. Neuroendocrine tumor in the lung of a captive black spider monkey (Ateles paniscus).

    Science.gov (United States)

    Cho, Ho-Seong; Kim, Yeong-Seob; Choi, Chan; Lee, Jae-Hyuk; Kurkure, Nitin V; Subramanian, Madhan; Park, Nam-Yong

    2007-07-01

    This paper describes a neuroendocrine (NE) tumor of the lung that was observed during the necropsy of a 14-year-old female black spider monkey (Ateles paniscus) with sudden death. Grossly, multifocal firm and coalescing nodular masses were observed in the lung. The histological examination showed the tumor to be an typical NE tumor with polygonal cells grouped in small solid aggregates, with regularly sized, spherical, centrally placed nuclei with modest, lightly granular cytoplasm suspended in a fibrovascular stroma. The immunohistochemical examination revealed the tumor to be positive for cytokeratin, chromogranin A and synaptophysin, and negative for CD56. To the best of our knowledge, this is the first report of NE tumor in the lung of the black spider monkey.

  20. Detection of circulating tumor cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Annkathrin eHanssen

    2015-09-01

    Full Text Available Lung Cancer is the most common cause of cancer related deaths that frequently metastasizes prior to disease diagnosis. Circulating tumor cells (CTCs are found in many different types of epithelial tumors and are of great clinical interest in terms of prognosis and therapy intervention. Here, we present and discuss EpCAM-dependent and -independent capture of CTCs in non-small cell lung cancer (NSCLC and the clinical relevance of CTC detection and characterization. Taking blood samples and analyzing CTCs as liquid biopsy might be a far less invasive diagnostic strategy than biopsies of lung tumors or metastases. Moreover, sequential blood sampling allows to study the dynamic changes of tumor cells during therapy, in particular the development of resistant tumor cell clones.

  1. Spontaneous Formation of Tumorigenic Hybrids between Breast Cancer and Multipotent Stromal Cells Is a Source of Tumor Heterogeneity

    OpenAIRE

    Rappa, Germana; Mercapide, Javier; Lorico, Aurelio

    2012-01-01

    Breast cancer progression involves cancer cell heterogeneity, with generation of invasive/metastatic breast cancer cells within populations of nonmetastatic cells of the primary tumor. Sequential genetic mutations, epithelial-to-mesenchymal transition, interaction with local stroma, and formation of hybrids between cancer cells and normal bone marrow–derived cells have been advocated as tumor progression mechanisms. We report herein the spontaneous in vitro formation of heterotypic hybrids be...

  2. A preclinical study of boron neutron capture therapy (BNCT) of spontaneous tumors in cats at RA-6 in Argentina

    International Nuclear Information System (INIS)

    Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Schwint, Amanda E.; Calzetta, Osvaldo A.; Blaumann, Hernan R.; Longhino, J.; Rao, Monica; Cantarelli, Maria de los A.

    2005-01-01

    BNCT is a binary treatment modality that combines irradiation with a thermal or epithermal neutron beam with tumor-seeking, boron containing drugs to produce selective irradiation of tumor tissue. Having demonstrated that BNCT mediated by boronophenylalanine (BPA) induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of RA-1. Having demonstrated partial tumor control with no radio toxic effects, the aim of the present study was to evaluate the effect of BPA-BNCT on tumor and normal tissue in 3 cases of spontaneous SCC in feline patients employing a higher neutron fluence than in the previous study. The present study was performed at RA-6 with the thermalized epithermal neutron beam. All three irradiations were successful. Except for an initial, moderate and reversible mucositis, no significant radio toxic effects were observed in terms of clinical follow-up, histological examination, biochemical analysis and assessment of autopsy material. Partial tumor control was evidenced in terms of growth inhibition and partial necrosis and improvement in the quality of life during the survival period. Optimization of the therapeutic efficacy of BNCT would require improvement in boron tumor targeting and strategies to increase in-depth dose in large tumors. (author)

  3. Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients

    International Nuclear Information System (INIS)

    Krawczyk, Natalia; Fehm, Tanja; Hartkopf, Andreas; Banys, Malgorzata; Meier-Stiegen, Franziska; Staebler, Annette; Wallwiener, Markus; Röhm, Carmen; Hoffmann, Juergen; Hahn, Markus

    2014-01-01

    An imbalance between cell proliferation and programmed cell death can result in tumor growth. Although most systemic cytotoxic agents induce apoptosis in tumor cells, a high apoptotic rate in primary breast cancer correlates with poor prognosis. The aim of this study was to investigate the incidence and the prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients who either underwent primary surgery or primary systemic chemotherapy (PST). A total of 383 primary breast cancer patients with viable DTC in the BM were included into this study. Eighty-five patients were initially treated with primary systemic chemotherapy whereas 298 patients underwent surgery first. Detection of apoptotic DTC were performed by immunocytochemistry using the M30 antibody which detects a neo-epitope expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The median follow up was 44 months (range 10–88 months). Eighty-two of 298 (27%) primary operated patients and 41 of 85 (48%) patients treated with primary systemic systemic therapy had additional apoptotic DTC (M30 positive). In the neoadjuvant group M30-positive patients were less likely to suffer relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). In contrast, the detection of apoptotic DTC in patients treated by primary surgery was significantly associated with poor overall survival (5% vs. 12% of the events, p = 0.008). Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in patients with PST may be induced by the cytotoxic agents. Thus, both spontaneous and chemotherapy-induced apoptosis may have different prognostic significance

  4. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

    Directory of Open Access Journals (Sweden)

    Ferrone Soldano

    2007-06-01

    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  5. Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

    Directory of Open Access Journals (Sweden)

    Chang Thomas

    2007-10-01

    Full Text Available Abstract Background Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. Methods Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5 were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. Results Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. Conclusion Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

  6. Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

    International Nuclear Information System (INIS)

    Collins, Brian T; Levy, Elliot; Chang, Thomas; Jamis-Dow, Carlos; Banovac, Filip; Anderson, Eric D; Erickson, Kelly; Reichner, Cristina A; Collins, Sean P; Gagnon, Gregory J; Dieterich, Sonja; McRae, Don A; Zhang, Ying; Yousefi, Shadi

    2007-01-01

    Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors

  7. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

    Science.gov (United States)

    Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

  8. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    International Nuclear Information System (INIS)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-01-01

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

  9. Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer.

    Science.gov (United States)

    Okamura, Kyoko; Takayama, Koichi; Izumi, Miiru; Harada, Taishi; Furuyama, Kazuto; Nakanishi, Yoichi

    2013-04-01

    Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2 ng/mL CEA and 3.5 ng/mL CYFRA 21-1 and twice these respective levels (6.4 ng/mL and 7.0 ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes' theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%], and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1, or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should

  10. Integrating the molecular background of targeted therapy and immunotherapy in lung cancer: a way to explore the impact of mutational landscape on tumor immunogenicity.

    Science.gov (United States)

    Pilotto, Sara; Molina-Vila, Miguel Angel; Karachaliou, Niki; Carbognin, Luisa; Viteri, Santiago; González-Cao, Maria; Bria, Emilio; Tortora, Giampaolo; Rosell, Rafael

    2015-12-01

    The results of randomized clinical trials employing immune checkpoint inhibitors for pre-treated advanced non-small-cell lung cancer (NSCLC) have recently revolutionised the standard available option for this disease setting. Nevertheless, the validation of reliable predictive biomarkers, able to define that proportion of patients most likely to benefit from immunotherapy, represents a crucial and still unsolved issue. This intensive research aimed at selecting potentially predictive biomarkers for immunotherapy is developed together with a wide range of analyses investigating the molecular profiling of lung cancer, leading to the spontaneous question of how these two parallel aspects of the same disease may coexist and influence one another. The potential impact of the mutational landscape of lung cancer on tumor immunogenicity (in both oncogene-addicted and molecularly unselected disease) will be explored and discussed in this review in order to begin to answer the unsolved questions.

  11. Calorie restriction reduces the incidence of radiation-induced myeloid leukemia and spontaneous tumor

    International Nuclear Information System (INIS)

    Yoshida, Kazuko

    1999-01-01

    The host-defense mechanisms against cancers are known to be modulated by changing the environmental factor(s). The spontaneous incidence of myeloid leukemia is about 1% in C3H/He mice, and the incidence increases up to 23.3% when a single dose of radiation, 3 Gy X-ray, is exposed to a whole-body. Since calorie restriction was known to reduce the incidence of spontaneous tumors, a question as to whether such radiation induced-increase of myeloid leukemia would be also decreased by calorie restriction, was aimed to answer to elucidate possible mechanism of radiation-induced myeloid leukemia. By the calorie restriction, the incidence of myeloid leukemia was significantly decreased; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the latent period of the myeloid leukemia in the groups for calorie restriction was significantly extended at a greater extent as compared with the control diet groups. Number of hematopoietic stem cells, the possible target cells for radiation-induced leukemias, in the groups for the calorie restriction demonstrated a significant decrease, especially in the spleen, as compared with that in the control, when the evaluation was made at the time of radiation exposure. Then, we examined whether the decreased number of target cells at the time of exposure is caused by the reduction of radiation-induced myeloid leukemia with caloric restriction. The third restricted groups were fed 65 kcal diet (restricted diet) for the first 4 weeks i.e. from 6 weeks to 10 weeks old, then, the mice were fed with control diet after radiation. The incidence of myeloid leukemia in this group was slightly decreased but did not show statistically significance. Therefore, the caloric restriction seems to be more effective in the promotion stage than the initiation stage on radiation-induced leukemogenesis. It is well known that C3H/He mice develop hepatoma spontaneously

  12. Calorie restriction reduces the incidence of radiation-induced myeloid leukemia and spontaneous tumor

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Kazuko [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    The host-defense mechanisms against cancers are known to be modulated by changing the environmental factor(s). The spontaneous incidence of myeloid leukemia is about 1% in C3H/He mice, and the incidence increases up to 23.3% when a single dose of radiation, 3 Gy X-ray, is exposed to a whole-body. Since calorie restriction was known to reduce the incidence of spontaneous tumors, a question as to whether such radiation induced-increase of myeloid leukemia would be also decreased by calorie restriction, was aimed to answer to elucidate possible mechanism of radiation-induced myeloid leukemia. By the calorie restriction, the incidence of myeloid leukemia was significantly decreased; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the latent period of the myeloid leukemia in the groups for calorie restriction was significantly extended at a greater extent as compared with the control diet groups. Number of hematopoietic stem cells, the possible target cells for radiation-induced leukemias, in the groups for the calorie restriction demonstrated a significant decrease, especially in the spleen, as compared with that in the control, when the evaluation was made at the time of radiation exposure. Then, we examined whether the decreased number of target cells at the time of exposure is caused by the reduction of radiation-induced myeloid leukemia with caloric restriction. The third restricted groups were fed 65 kcal diet (restricted diet) for the first 4 weeks i.e. from 6 weeks to 10 weeks old, then, the mice were fed with control diet after radiation. The incidence of myeloid leukemia in this group was slightly decreased but did not show statistically significance. Therefore, the caloric restriction seems to be more effective in the promotion stage than the initiation stage on radiation-induced leukemogenesis. It is well known that C3H/He mice develop hepatoma spontaneously

  13. Laser-induced thermotherapy of lung metastases and primary lung tumors; Laserinduzierte Thermotherapie von Lungenmetastasen und primaeren Lungentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J. (Institut fuer Diagnostische und Interventionelle Radiologie, Klinikum der J.-W.-Goethe-Universitaet Frankfurt; Institut fuer Diagnostische und Interventionelle Radiologie, Klinikum der J.-W.-Goethe-Universitaet, Theodor-Stern-Kai 7, 60590, Frankfurt); Fieguth, H.G. (Klinik fuer Thorax-, Herz- und thorakale Gefaesschirurgie, Klinikum der J.-W.-Goethe-Universitaet Frankfurt); Eichler, K.; Straub, R.; Lehnert, T.; Zangos, S.; Mack, M. (Institut fuer Diagnostische und Interventionelle Radiologie, Klinikum der J.-W.-Goethe-Universitaet Frankfurt)

    2004-07-01

    We present laser-induced thermotherapy (LITT) of primary and secondary lung tumors analysing indications and technical concepts. Thirty patients with lung metastases of different primary tumors (n=24) as well as localized lung tumors (n=6) were prospectively treated in 41 sessions using laser-induced thermotherapy (LITT). An MR-compatible puncture system was used with direct puncture technique. The puncture was performed via CT guidance in care vision technique. Eight patients were thermoablated using MR tomographical monitoring, 22 patients using CT monitoring. Local therapy effects, tumor control rate, side effects, complications, and survival were evaluated. In 74% of cases (28/38 lesions) of 24 patients with lung metastases and in all cases of the 6 patients with lung carcinoma a complete local ablation could be achieved. The complication rate (pneumothorax) was 9,8%. One patient with bronchial carcinoma had to be thoracotomized and resected. 93% of the patients are still alive. Percutaneous LITT of lung tumors permits a complete ablation of lung metastases and lung carcinomas with a low complication rate. Indications for the procedure were defined for patients with no more than 5 metastases up to 3 cm in size. (orig.) [German] Wir stellen nachfolgend die Ergebnisse der laserinduzierten Thermotherapie (LITT) primaerer und sekundaerer Lungentumoren vor und analysieren die Indikationsstellung und die Interventionstechnik. Dreissig Patienten mit Lungenmetastasen unterschiedlicher Primaertumoren (n=24) sowie lokalisierten Bronchialkarzinomen (n=6) wurden prospektiv in 41 Sitzungen mittels MR-gesteuerter LITT therapiert. Zum Einsatz kam ein MR-kompatibles Punktionssystem in direkter Punktionstechnik; die Punktion erfolgte jeweils unter CT-Steuerung in Care-vision-Technik. Acht Patienten wurden mittels MR-tomographischem Monitoring thermoablatiert, 22 Patienten mittels CT-Monitoring. Evaluiert wurden die lokalen Therapieeffekte, Tumorkontrollrate, und die Frage von

  14. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Eric D. Johnson

    2016-12-01

    Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

  15. Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer.

    Science.gov (United States)

    Ma, Yunxia; Chen, Yuan; Li, Yong; Grün, Katja; Berndt, Alexander; Zhou, Zhongwei; Petersen, Iver

    2018-03-06

    Cystatin A ( CSTA ), belonging to type 1 cystatin super-family, is expressed primarily in epithelial and lymphoid tissues for protecting cells from proteolysis of cytoplasmic and cytoskeletal proteins by cathepsins B, H and L. CSTA acts as a tumor suppressor in esophageal cancer, however, its role in lung cancer has not yet been elucidated. Here we found that CSTA was down-regulated in all lung cancer cell lines compared to normal lung epithelial cells. CSTA was restored in most lung cancer cell lines after treatment with demethylation agent 5-aza-2-deoxycytidine and deacetylation agent Trichostatin. Bisulfite sequencing revealed that CSTA was partially methylated in the promoter and exon 1. In primary lung tumors, squamous cell carcinoma (SCC) significantly expressed more CSTA compared to adenocarcinoma (pgrade (ptransition (MET) and prevented the TGF-β1-induced epithelial to mesenchymal transition (EMT) through inhibiting the ERK/MAPK pathway. In conclusion, our date indicate 1) epigenetic regulation is associated with CSTA gene silencing; 2) CSTA exerts tumor suppressive function through inhibiting MAPK and AKT pathways; 3) Overexpression of CSTA leads to MET and prevents TGF-β1-induced EMT by modulating the MAPK pathway; 4) CSTA may be a potential biomarker for lung SCC and tumor differentiation.

  16. SU-E-J-267: Change in Mean CT Intensity of Lung Tumors During Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Mahon, R; Tennyson, N; Weiss, E; Hugo, G [Virginia Commonwealth University, Richmond, VA (United States)

    2015-06-15

    Purpose: To evaluate CT intensity change of lung tumors during radiation therapy. Methods: Repeated 4D CT images were acquired on a CT simulator during the course of therapy for 27 lung cancer patients on IRB approved protocols. All subjects received definitive radiation treatment ± chemotherapy. CT scans were completed prior to treatment, and 2–7 times during the treatment course. Primary tumor was delineated by an experienced Radiation Oncologist. Contours were thresholded between −100 HU and 200 HU to remove airways and bone. Correlations between the change in the mean tumor intensity and initial tumor intensity, SUVmax, and tumor volume change rate were investigated. Reproducibility was assessed by evaluating the variation in mean intensity over all phases in 4DCT, for a subgroup of 19 subjects. Results: Reproducibility of tumor intensity between phases as characterized by the root mean square of standard deviation across 19 subjects was 1.8 HU. Subjects had a mean initial tumor intensity of 16.5 ± 11.6 HU and an overall reduction in HU by 10.3 ± 8.5 HU. Evaluation of the changes in tumor intensity during treatment showed a decrease of 0.3 ± 0.3 HU/day for all subjects, except three. No significant correlation was found between change in HU/day and initial HU intensity (p=0.53), initial PET SUVmax (p=0.69), or initial tumor volume (p=0.70). The rate of tumor volume change was weakly correlated (R{sup 2}=0.05) with HU change (p=0.01). Conclusion: Most lung cancer subjects showed a marked trend of decreasing mean tumor CT intensity throughout radiotherapy, including early in the treatment course. Change in HU/day is not correlated with other potential early predictors for response, such as SUV and tumor volume change. This Result supports future studies to evaluate change in tumor intensity on CT as an early predictor of response.

  17. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Nitrilase 1 modulates lung tumor progression in vitro and in vivo.

    Science.gov (United States)

    Wang, Yong Antican; Sun, Yunguang; Le Blanc, Justin M; Solomides, Charalambos; Zhan, Tingting; Lu, Bo

    2016-04-19

    Uncovering novel growth modulators for non-small cell lung cancer (NSCLC) may lead to new therapies for these patients. Previous studies suggest Nit1 suppresses chemically induced carcinogenesis of the foregut in a mouse model. In this study we aimed to determine the role of Nit1 in a transgenic mouse lung cancer model driven by a G12D Kras mutation. Nit1 knockout mice (Nit1-/-) were crossed with KrasG12D/+ mice to investigate whether a G12D Kras mutation and Nit1 inactivation interact to promote or inhibit the development of NSCLC. We found that lung tumorigenesis was suppressed in the Nit1-null background (Nit1-/-:KrasG12D/+). Micro-CT scans and gross tumor measurements demonstrated a 5-fold reduction in total tumor volumes compared to Nit1+/+KrasG12D/+ (p<0.01). Furthermore, we found that Nit1 is highly expressed in human lung cancer tissues and cell lines and use of siRNA against Nit1 decreased overall cell survival of lung cancer cells in culture. In addition, cisplatin response was enhanced in human lung cancer cells when Nit1 was knocked down and Nit1-/-:KrasG12D/+ tumors showed increased sensitivity to cisplatin in vivo. Together, our data indicate that Nit1 may play a supportive role in the modulation of lung tumorigenesis and represent a novel target for NSCLCs treatment.

  19. The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Linjie Liu

    2017-01-01

    Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

  20. Acute aortic occlusion due to tumor embolism in a patient with lung malignancy

    Directory of Open Access Journals (Sweden)

    Stella Lioudaki

    2017-07-01

    Full Text Available Objectives: Acute lower limb ischemia caused by tumor embolization is rare, despite the fact that cancer is a common cause of hypercoagulability predisposing to venous thrombosis. Arterial embolization is mostly associated with intracardiac tumors while lung malignancies are the second most common cause of tumor embolism. Methods: In this report, we present a male patient who developed acute bilateral lower limb ischemia in the immediate postoperative period after a thoracotomy for attempted left upper lobe resection for lung cancer. Results: The patient was treated with a subclavian-bifemoral bypass, since an initial attempted embolectomy was unsuccessful. Histopathological characteristics of thrombus obtained during embolectomy were consistent with the histopathology of the primary tumor. Conclusion: Acute ischemia is an emergency that should be diagnosed and treated immediately. Interestingly, in this case, the presence of epidural anesthesia masked the initial symptoms and delayed diagnosis. Preoperative assessment with transesophageal echocardiography may reveal patients at high risk for tumor embolism.

  1. Nicotine promotes tumor growth and metastasis in mouse models of lung cancer.

    Directory of Open Access Journals (Sweden)

    Rebecca Davis

    2009-10-01

    Full Text Available Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p. injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7% as compared to the vehicle treated mice (19.5%. Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7 nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT in cultured lung, breast and pancreatic cancer cells. This study

  2. An artificial neural network (ANN)-based lung-tumor motion predictor for intrafractional MR tumor tracking.

    Science.gov (United States)

    Yun, Jihyun; Mackenzie, Marc; Rathee, Satyapal; Robinson, Don; Fallone, B G

    2012-07-01

    To address practical issues of implementing artificial neural networks (ANN) for lung-tumor motion prediction in MRI-based intrafractional lung-tumor tracking. A feedforward four-layered ANN structure is used to predict future tumor positions. A back-propagation algorithm is used for ANN learning. Adaptive learning is incorporated by continuously updating weights and learning rate during prediction. An ANN training scheme specific for MRI-based tracking is developed. A multiple-ANN structure is developed to reduce tracking failures caused by the lower imaging rates of MRI. We used particle swarm optimization to optimize the ANN structure and initial weights (IW) for each patient and treatment fraction. Prediction accuracy is evaluated using the 1D superior-inferior lung-tumor motions of 29 lung cancer patients for system delays of 120-520 ms, in increments of 80 ms. The result is compared with four different scenarios: (1), (2) ANN structure optimization + with∕without IW optimization, and (3), (4) no ANN structure optimization + with∕without IW optimization, respectively. An additional simulation is performed to assess the value of optimizing the ANN structure for each treatment fraction. For 120-520 ms system delays, mean RMSE values (ranges 0.0-2.8 mm from 29 patients) of 0.5-0.9 mm are observed, respectively. Using patient specific ANN structures, a 30%-60% decrease in mean RMSE values is observed as a result of IW optimization, alone. No significant advantages in prediction performance are observed, however, by optimizing for each fraction. A new ANN-based lung-tumor motion predictor is developed for MRI-based intrafractional tumor tracking. The prediction accuracy of our predictor is evaluated using a realistic simulated MR imaging rate and system delays. For 120-520 ms system delays, mean RMSE values of 0.5-0.9 mm (ranges 0.0-2.8 mm from 29 patients) are achieved. Further, the advantage of patient specific ANN structure and IW in lung-tumor motion

  3. Imaging of tumor viability in lung cancer. Initial results using 23Na-MRI

    International Nuclear Information System (INIS)

    Henzler, T.; Apfaltrer, P.; Haneder, S.; Schoenberg, S.O.; Fink, C.; Konstandin, S.; Schad, L.; Schmid-Bindert, G.; Manegold, C.; Wenz, F.

    2012-01-01

    23 Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23 Na-MRI in patients with lung cancer. Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23 Na-MRI images was proven by comparison and fusion of 23 Na-MRI with 1 H-MR, CT and FDG-PET-CT images. 23 Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). All 23 Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23 Na-MRI images with 1 H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 x 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 x 103 and 1.10, respectively. 23 Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response. (orig.)

  4. The let-7 microRNA reduces tumor growth in mouse models of lung cancer.

    Science.gov (United States)

    Esquela-Kerscher, Aurora; Trang, Phong; Wiggins, Jason F; Patrawala, Lubna; Cheng, Angie; Ford, Lance; Weidhaas, Joanne B; Brown, David; Bader, Andreas G; Slack, Frank J

    2008-03-15

    MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.

  5. WE-AB-303-08: Direct Lung Tumor Tracking Using Short Imaging Arcs

    International Nuclear Information System (INIS)

    Shieh, C; Huang, C; Keall, P; Feain, I

    2015-01-01

    Purpose: Most current tumor tracking technologies rely on implanted markers, which suffer from potential toxicity of marker placement and mis-targeting due to marker migration. Several markerless tracking methods have been proposed: these are either indirect methods or have difficulties tracking lung tumors in most clinical cases due to overlapping anatomies in 2D projection images. We propose a direct lung tumor tracking algorithm robust to overlapping anatomies using short imaging arcs. Methods: The proposed algorithm tracks the tumor based on kV projections acquired within the latest six-degree imaging arc. To account for respiratory motion, an external motion surrogate is used to select projections of the same phase within the latest arc. For each arc, the pre-treatment 4D cone-beam CT (CBCT) with tumor contours are used to estimate and remove the contribution to the integral attenuation from surrounding anatomies. The position of the tumor model extracted from 4D CBCT of the same phase is then optimized to match the processed projections using the conjugate gradient method. The algorithm was retrospectively validated on two kV scans of a lung cancer patient with implanted fiducial markers. This patient was selected as the tumor is attached to the mediastinum, representing a challenging case for markerless tracking methods. The tracking results were converted to expected marker positions and compared with marker trajectories obtained via direct marker segmentation (ground truth). Results: The root-mean-squared-errors of tracking were 0.8 mm and 0.9 mm in the superior-inferior direction for the two scans. Tracking error was found to be below 2 and 3 mm for 90% and 98% of the time, respectively. Conclusions: A direct lung tumor tracking algorithm robust to overlapping anatomies was proposed and validated on two scans of a lung cancer patient. Sub-millimeter tracking accuracy was observed, indicating the potential of this algorithm for real-time guidance

  6. The level of serum tumor makers and bone metastases of lung cancer correlation

    International Nuclear Information System (INIS)

    Li Li; Jin Jianhua

    2014-01-01

    Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. 99m Tc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ 2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by 99m Tc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of 99m Tc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence of

  7. Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Xia, Jingen; Zhang, Heng; Sun, Bing; Yang, Rui; He, Hangyong; Zhan, Qingyuan

    2014-06-01

    It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

  8. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  9. Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration

    International Nuclear Information System (INIS)

    Barnes, Elizabeth A.; Murray, Brad R.; Robinson, Donald M.; Underwood, Lori J.; Hanson, John; Roa, Wilson H.Y.

    2001-01-01

    Purpose:To examine the dosimetric benefit of self-gated radiotherapy at deep-inspiration breath hold (DIBH) in the treatment of patients with non-small-cell lung cancer (NSCLC). The relative contributions of tumor immobilization at breath hold (BH) and increased lung volume at deep inspiration (DI) in sparing high-dose lung irradiation (≥20 Gy) were examined. Methods and Materials:Ten consecutive patients undergoing radiotherapy for Stage I-IIIB NSCLC who met the screening criteria were entered on this study. Patients were instructed to BH at DI without the use of external monitors or breath-holding devices (self-gating). Computed tomography (CT) scans of the thorax were performed during free breathing (FB) and DIBH. Fluoroscopy screened for reproducible tumor position throughout DIBH, and determined the maximum superior-inferior (SI) tumor motion during both FB and DIBH. Margins used to define the planning target volume (PTV) from the clinical target volume included 1 cm for setup error and organ motion, plus an additional SI margin for tumor motion, as determined from fluoroscopy. Three conformal treatment plans were then generated for each patient, one from the FB scan with FB PTV margins, a second from the DIBH scan with FB PTV margins, and a third from the DIBH scan with DIBH PTV margins. The percent of total lung volume receiving ≥20 Gy (using a prescription dose of 70.9 Gy to isocenter) was determined for each plan. Results:Self-gating at DIBH was possible for 8 of the 10 patients; 2 patients were excluded, because they were not able to perform a reproducible DIBH. For these 8 patients, the median BH time was 23 (range, 19-52) s. The mean percent of total lung volume receiving ≥20 Gy under FB conditions (FB scan with FB PTV margins) was 12.8%. With increased lung volume alone (DIBH scan with FB PTV margins), this was reduced to 11.0%, tending toward a significant decrease in lung irradiation over FB (p=0.086). With both increased lung volume and tumor

  10. Cyclin D expression in plutonium-induced lung tumors in F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.; Kelly, G. [SouthWest Scientific Resources, Inc., Albuquerque, NM (United States)

    1995-12-01

    The genetic mechanisms responsible for {alpha}-radiation-induced lung cancer in rats following inhalation of {sup 239}Pu is an ongoing area of research in our laboratory. Previous studies have examined the status of the p53 gene by immunohistochemistry. Only two tumors (2/26 squamous cell carcinomas) exhibited detectable levels of p53 products. Both were the result of mutations in codons 280 and 283. More recent studies of X-ray-induced lung tumors in rats showed a similar lack of involvement of p53. In conclusion, we found that {alpha}-radiation-induced rat lung tumors have a high incidence (31 of 39) of cyclin D{sub 1} overexpression.

  11. Failure of the cultivated mushroom (Agaricus bisporus) to induce tumors in the A/J mouse lung tumor model

    DEFF Research Database (Denmark)

    Pilegaard, Kirsten; Kristiansen, E.; Meyer, Otto A.

    1997-01-01

    We studied whether the cultivated mushroom (Agaricus bisporus) or 4-(carboxy)phenylhydrazine (CP) induce lung adenomas in the A/J mouse lung tumor model. For 26 weeks female mice were fed a semisynthetic diet where 11 or 22% of the diet was replaced by freeze-dried mushrooms. The intake...... of the mushroom diets was equivalent to an intake of agaritine, the major phenylhydrazine derivative occurring in the mushroom, of 92 or 166 mg/kg body weight per day. The intake of CP was 106 mg/kg body weight per day. Neither the;freeze-dried mushroom nor CP induced statistically significant increased numbers...

  12. Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

    Science.gov (United States)

    Güldner, Andreas; Kiss, Thomas; Bluth, Thomas; Uhlig, Christopher; Braune, Anja; Carvalho, Nadja; Quast, Theresa; Rentzsch, Ines; Huhle, Robert; Spieth, Peter; Richter, Torsten; Saddy, Felipe; Rocco, Patricia R M; Kasper, Michael; Koch, Thea; Pelosi, Paolo; de Abreu, Marcelo Gama

    2015-03-01

    To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

  13. Therapy monitoring using dynamic MRI: Analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Plathow, Christian [Eberhard-Karls University Tuebingen, Department of Diagnostic Radiology, Tuebingen (Germany); German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Hof, Holger; Kuhn, Sabine [University of Heidelberg, Department of Radiation Therapy, Clinic for Thoracic Diseases, Heidelberg (Germany); Puderbach, Michael; Ley, Sebastian; Biederer, Juergen; Kauczor, Hans-Ulrich [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Claussen, Claus D.; Schaefer, Juergen [Eberhard-Karls University Tuebingen, Department of Diagnostic Radiology, Tuebingen (Germany); Huber, Peter E. [University of Heidelberg, Department of Radiation Therapy, Clinic for Thoracic Diseases, Heidelberg (Germany); German Cancer Research Center, Department of Radiation Oncology, Heidelberg (Germany); Tuengerthal, Siegfried [University of Heidelberg, Department of Radiology, Heidelberg (Germany)

    2006-09-15

    A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2{+-}0.9 cm if the tumor was located in the lower LR (middle LR: 5.5{+-}0.8 cm; upper LR: 6.0{+-}0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P<0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5{+-}0.6 vs. 2.0{+-}0.3 cm (middle LR; P<0.05) vs. 0.7{+-}0.2 cm (upper LR; P<0.01). After RT, tumor mobility was significantly reduced in the lower LR (P<0.01) and in T2 tumor patients (P<0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter. (orig.)

  14. Therapy monitoring using dynamic MRI: Analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy

    International Nuclear Information System (INIS)

    Plathow, Christian; Hof, Holger; Kuhn, Sabine; Puderbach, Michael; Ley, Sebastian; Biederer, Juergen; Kauczor, Hans-Ulrich; Claussen, Claus D.; Schaefer, Juergen; Huber, Peter E.; Tuengerthal, Siegfried

    2006-01-01

    A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2±0.9 cm if the tumor was located in the lower LR (middle LR: 5.5±0.8 cm; upper LR: 6.0±0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P<0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5±0.6 vs. 2.0±0.3 cm (middle LR; P<0.05) vs. 0.7±0.2 cm (upper LR; P<0.01). After RT, tumor mobility was significantly reduced in the lower LR (P<0.01) and in T2 tumor patients (P<0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter. (orig.)

  15. Fuzzy logic-based tumor-marker profiles improved sensitivity in the diagnosis of lung cancer.

    Science.gov (United States)

    Schneider, Joachim; Bitterlich, Norman; Velcovsky, Hans-Georg; Morr, Harald; Katz, Norbert; Eigenbrodt, Erich

    2002-06-01

    The aim of this study was to improve the diagnostic efficiency of tumor markers in the diagnosis of lung cancer, by the mathematical evaluation of a tumor marker profile employing fuzzy logic modelling. A panel of four tumor markers, i.e., carcinoembryonic antigen (CEA), cytokeratin 19 antibody (CYFRA 21-1), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC) and, additionally, C-reactive protein (CRP), was measured in 175 newly diagnosed lung cancer patients with different histological types and stages. Results were compared with those in 120 control subjects, including 27 with chronic obstructive pulmonary diseases (COPD), 65 with pneumoconiosis, and 11 persons with acute inflammatory lung diseases. A classificator was developed using a fuzzy-logic rule-based system. Application of the fuzzy-logic rule-based system to the tumor marker values of CYFRA 21-1, NSE, and CRP yielded an increase in sensitivity of approximately 20%, i.e., 92%, compared with that of the best single marker, CYFRA 21-1(sensitivity, 72%). The corresponding specificity was 95%. The fuzzy classificator significantly improved the sensitivity of the tumor marker panel in stages I and IIIa for non-small-cell lung cancer, as well as in "limited disease" status for small-cell lung cancer. Also, the diagnosis of other stages of lung cancer was enhanced. Fuzzy-logic analysis was proven to be more powerful than the measurement of single markers alone or combinations using multiple logistic regression analysis of all markers. Therefore, fuzzy logic offers a promising diagnostic tool to improve tumor marker efficiency.

  16. Safety of Simultaneous Bilateral Pulmonary Resection for Metastatic Lung Tumors.

    Science.gov (United States)

    Matsubara, Taichi; Toyokawa, Gouji; Kinoshita, Fumihiko; Haratake, Naoki; Kozuma, Yuka; Akamine, Takaki; Takamori, Shinkichi; Hirai, Fumihiko; Tagawa, Tetsuzo; Okamoto, Tatsuro; Maehara, Yoshihiko

    2018-03-01

    We investigated the safety of simultaneous bilateral lung resection for lung metastases. We retrospectively analyzed 185 patients with pulmonary metastases who underwent unilateral or bilateral pulmonary resection from August 2009 to December 2016 at a single institution. Single-stage bilateral lung resection was undertaken in 19 patients, and the other 166 patients underwent unilateral pulmonary resection, including 20 patients who underwent repeated resections for synchronous or metachronous metastases. Operative time and drainage days in the bilateral group were significantly longer than those in the unilateral group (220±20 vs. 152±6.9 min: ppulmonary metastasectomy appears to be safe as long as only wedge resection is performed on at least one side. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. On using an adaptive neural network to predict lung tumor motion during respiration for radiotherapy applications

    International Nuclear Information System (INIS)

    Isaksson, Marcus; Jalden, Joakim; Murphy, Martin J.

    2005-01-01

    In this study we address the problem of predicting the position of a moving lung tumor during respiration on the basis of external breathing signals--a technique used for beam gating, tracking, and other dynamic motion management techniques in radiation therapy. We demonstrate the use of neural network filters to correlate tumor position with external surrogate markers while simultaneously predicting the motion ahead in time, for situations in which neither the breathing pattern nor the correlation between moving anatomical elements is constant in time. One pancreatic cancer patient and two lung cancer patients with mid/upper lobe tumors were fluoroscopically imaged to observe tumor motion synchronously with the movement of external chest markers during free breathing. The external marker position was provided as input to a feed-forward neural network that correlated the marker and tumor movement to predict the tumor position up to 800 ms in advance. The predicted tumor position was compared to its observed position to establish the accuracy with which the filter could dynamically track tumor motion under nonstationary conditions. These results were compared to simplified linear versions of the filter. The two lung cancer patients exhibited complex respiratory behavior in which the correlation between surrogate marker and tumor position changed with each cycle of breathing. By automatically and continuously adjusting its parameters to the observations, the neural network achieved better tracking accuracy than the fixed and adaptive linear filters. Variability and instability in human respiration complicate the task of predicting tumor position from surrogate breathing signals. Our results show that adaptive signal-processing filters can provide more accurate tumor position estimates than simpler stationary filters when presented with nonstationary breathing motion

  18. Real-time tumor tracking in the lung using an electromagnetic tracking system.

    Science.gov (United States)

    Shah, Amish P; Kupelian, Patrick A; Waghorn, Benjamin J; Willoughby, Twyla R; Rineer, Justin M; Mañon, Rafael R; Vollenweider, Mark A; Meeks, Sanford L

    2013-07-01

    To describe the first use of the commercially available Calypso 4D Localization System in the lung. Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R(2)) were tabulated for all 42 tracks. For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual

  19. Prognosis in patients with non-small cell lung cancer and satellite tumors.

    Science.gov (United States)

    Kocaturk, C I; Gunluoglu, M Z; Cansever, L; Dincer, I S; Bedirhan, M A

    2011-09-01

    Aim of the study was to identify factors affecting survival in patients with lung cancer and satellite tumors (ST). Between 2001 and 2008, there were 102 patients with synchronous multiple lung cancers among the 1355 lung resections performed in lung cancer patients. Satellite tumors were found to be near the primary lung cancer (PLC) in 29 patients. Complete resection was achieved in all patients, and the 5-year survival rate was 52 %. The independent "T" stages of the PLCs and STs did not affect survival ( P = 0.98 and P = 0.54, respectively). A distance between the PLC and ST longer or shorter than 2, 3, or 4 cm also did not affect survival ( P = 0.78, P = 0.57, and P = 0.62, respectively). The survival of patients treated with adjuvant therapy was significantly higher than that of patients who did not receive adjuvant therapy ( P = 0.0043). Satisfactory survival was achieved after surgical therapy for non-small cell lung cancer associated with ST. While the PLC and ST characteristics and the distance between tumors did not affect survival rates, the introduction of adjuvant chemotherapy with/without radiotherapy positively affected survival. © Georg Thieme Verlag KG Stuttgart · New York.

  20. The effectiveness of breath-holding to stabilize lung and pancreas tumors during radiosurgery

    International Nuclear Information System (INIS)

    Murphy, Martin J.; Martin, David; Whyte, Richard; Hai, Jenny; Ozhasoglu, Cihat; Le, Quynh-Thu

    2002-01-01

    Purpose: To evaluate the effect of breath-holding on the short-term reproducibility and long-term variability of tumor position during image-guided radiosurgery. Method: Thirteen patients have undergone single-fraction radiosurgery treatments during which the tumor was repeatedly imaged radiographically to observe its position. The imaging data were used to monitor the efficacy of breath-holding and to periodically readjust the alignment of the treatment beam with the tumor. These measurements have allowed the effects of breathing, heartbeat, patient movement, and instrumental uncertainties to be separately identified in the record of tumor position. Results: During inspiration breath-holding, the lung tumor position was reproducible to within 1 mm, on average, in the direction of maximum displacement during regular breathing, and to within 1.8 mm in three dimensions overall. The pancreas tumor position in three dimensions was reproducible to within 2.5 mm on average. Some patients showed a slow, steady drift of tumor position during the extended sequence of breath-holds, which was compensated by periodic retargeting of the treatment beam. Conclusion: Breath-holding can allow the reduction of tumor motion dosimetry margins to 2 mm or less for lung cancer treatments, provided that the treatment system can detect and adapt to long-term variations in the mean tumor position during a lengthy treatment fraction

  1. Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Peng Fang; Wang Jin; Zou Yi; Bao Yong; Huang Wenlin; Chen Guangming; Luo Xianrong; Chen Ming

    2011-01-01

    Objective: To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods: Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results: Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. (authors)

  2. Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice.

    Science.gov (United States)

    Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

    2010-02-01

    Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

  3. Automatic Lung Tumor Segmentation on PET/CT Images Using Fuzzy Markov Random Field Model

    Directory of Open Access Journals (Sweden)

    Yu Guo

    2014-01-01

    Full Text Available The combination of positron emission tomography (PET and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice’s similarity coefficient (DSC was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.

  4. The Potential Biomarkers and Immunological Effects of Tumor-Derived Exosomes in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shamila D. Alipoor

    2018-04-01

    Full Text Available Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite considerable achievements in lung cancer diagnosis and treatment, the global control of the disease remains problematic. In this respect, greater understanding of the disease pathology is crucially needed for earlier diagnosis and more successful treatment to be achieved. Exosomes are nano-sized particles secreted from most cells, which allow cross talk between cells and their surrounding environment via transferring their cargo. Tumor cells, just like normal cells, also secrete exosomes that are termed Tumor-Derived Exosome or tumor-derived exosome (TEX. TEXs have gained attention for their immuno-modulatory activities, which strongly affect the tumor microenvironment and antitumor immune responses. The immunological activity of TEX influences both the innate and adaptive immune systems including natural killer cell activity and regulatory T-cell maturation as well as numerous anti-inflammatory responses. In the context of lung cancer, TEXs have been studied in order to better understand the mechanisms underlying tumor metastasis and progression. As such, TEX has the potential to act both as a biomarker for lung cancer diagnosis as well as the response to therapy.

  5. Anti-tumor effects of gene therapy with GALV membrane fusion glycoprotein in lung adenocarcinoma.

    Science.gov (United States)

    Zhu, Bing; Yang, Jian-ru; Fu, Xin-ping; Jiang, Yue-quan

    2014-07-01

    This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus). Recombinant HSV-I plasmid carrying target transgene was constructed, and recombinant viral vector was generated in Vero cells using Lipofectamine transfection. Viral vector was introduced into lung adenocarcinoma A549 cells or human fetal fibroblast HFL-I GNHu 5 cells, or inoculated into human lung adenocarcinoma xenografts in nude mice. The anti-tumor and cytotoxic effects of GALV-FMG, the transgene, were examined in these cell and animal models. Expression of GALV-FMG in xenographs achieved 100 % tumorigenicity. Recombinant HSV-I viral vector also exhibited significant tumor cell killing effect in vitro. Relative survival rates of tumor cells treated with GALV-FMG or control vectors were, respectively, 20 and 70 %. GALV.fus has a potent anti-tumor effect against lung cancer both in vitro and in vivo. This anti-tumor potential provides foundation for further studies with this vector.

  6. Malignant ameloblastoma (metastatic ameloblastoma) in the lung: 3 cases of misdiagnosis as primary lung tumor with a unique growth pattern.

    Science.gov (United States)

    Bi, Rui; Shen, Lei; Zhu, Xiongzeng; Xu, Xiaoli

    2015-07-25

    Malignant ameloblastoma (metastatic ameloblastoma, MA) is currently defined as a distinct pathologic entity, MA, despite its histologically benign appearance. According to the new criteria, the histological and clinical features of MA are more homogenous. Here, we report three cases of histologically confirmed pulmonary MA. Two of the three patients complained of chest pain as the primary symptom, and the other case was detected upon the evaluation of pulmonary nodules found during a health examination after a local recurrence of mandible ameloblastoma. All three patients were female with an average age of 48 years. The intervals between the primary ameloblastoma and metastasis to the lung were 14 years, 19 years and 10 years, averaging 14.3 years. Prior to metastasis to the lung, only one patient experienced local recurrences, at 5 and 19 years after the primary tumor resection, while the other two patients both remained disease-free. Computed tomography (CT) or X-ray evaluation demonstrated multiple bilateral lung nodules ranging in size from several millimeters up to 2 cm. Histologically, the pulmonary metastatic tumors showed a unique growth pattern: the tumor cells grew among the interstitial alveoli but did not appear to destructively infiltrate the surrounding tissue. Immunohistochemically, the MA cells expressed squamous differentiation markers, such as CK10/13 and p63, while the alveolar epithelial cells stained for TTF1 and PE10. In this paper, we discuss the clinical behavior, differential diagnosis and unique growth pattern of pulmonary MA.

  7. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer.

    Science.gov (United States)

    Faget, Julien; Groeneveld, Svenja; Boivin, Gael; Sankar, Martial; Zangger, Nadine; Garcia, Miguel; Guex, Nicolas; Zlobec, Inti; Steiner, Loïc; Piersigilli, Alessandra; Xenarios, Ioannis; Meylan, Etienne

    2017-12-12

    Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1 + neutrophils to disease progression. Depletion experiments showed that Gr1 + cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration. Cxcl2 was produced mainly by neutrophils themselves in response to a factor secreted by Snail-expressing tumor cells. We therefore propose a vicious cycle encompassing neutrophils and Snail to maintain a deleterious tumor microenvironment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Julien Faget

    2017-12-01

    Full Text Available Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1 favor tumor growth, (2 reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3 alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration. Cxcl2 was produced mainly by neutrophils themselves in response to a factor secreted by Snail-expressing tumor cells. We therefore propose a vicious cycle encompassing neutrophils and Snail to maintain a deleterious tumor microenvironment.

  9. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    Science.gov (United States)

    1984-10-01

    intercellular attachments. After evaluation of a number of enzymes and enzyme mixtures including Protease I (Sigma), collagenase (Worthington), thermolysin ...in HPBS. At this time, the lung lobes are removed, minced and stirred with soybean trypsin inhibitor (1 mg/mL, Sigma) in the cold for an additional 30

  10. Anti-Tumor Effect of Cactus Polysaccharides on Lung Squamous ...

    African Journals Online (AJOL)

    Abbreviations: PTEN :phosphatase and tension homolog deleted on chromosome ten; NSCLC: Non-small-cell lung cancer; FBS :Phosphate buffered saline; MTT:3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PBS: Phosphate buffered saline; DMSO:Dimethyl sulfoxide; PI: Propidium iodide.

  11. SU-E-J-29: Audiovisual Biofeedback Improves Tumor Motion Consistency for Lung Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D; Pollock, S; Makhija, K; Keall, P [The University of Sydney, Camperdown, NSW (Australia); Greer, P [The University of Newcastle, Newcastle, NSW (Australia); Calvary Mater Newcastle Hospital, Newcastle, NSW (Australia); Arm, J; Hunter, P [Calvary Mater Newcastle Hospital, Newcastle, NSW (Australia); Kim, T [The University of Sydney, Camperdown, NSW (Australia); University of Virginia Health System, Charlottesville, VA (United States)

    2014-06-01

    Purpose: To investigate whether the breathing-guidance system: audiovisual (AV) biofeedback improves tumor motion consistency for lung cancer patients. This will minimize respiratory-induced tumor motion variations across cancer imaging and radiotherapy procedues. This is the first study to investigate the impact of respiratory guidance on tumor motion. Methods: Tumor motion consistency was investigated with five lung cancer patients (age: 55 to 64), who underwent a training session to get familiarized with AV biofeedback, followed by two MRI sessions across different dates (pre and mid treatment). During the training session in a CT room, two patient specific breathing patterns were obtained before (Breathing-Pattern-1) and after (Breathing-Pattern-2) training with AV biofeedback. In each MRI session, four MRI scans were performed to obtain 2D coronal and sagittal image datasets in free breathing (FB), and with AV biofeedback utilizing Breathing-Pattern-2. Image pixel values of 2D images after the normalization of 2D images per dataset and Gaussian filter per image were used to extract tumor motion using image pixel values. The tumor motion consistency of the superior-inferior (SI) direction was evaluated in terms of an average tumor motion range and period. Results: Audiovisual biofeedback improved tumor motion consistency by 60% (p value = 0.019) from 1.0±0.6 mm (FB) to 0.4±0.4 mm (AV) in SI motion range, and by 86% (p value < 0.001) from 0.7±0.6 s (FB) to 0.1±0.2 s (AV) in period. Conclusion: This study demonstrated that audiovisual biofeedback improves both breathing pattern and tumor motion consistency for lung cancer patients. These results suggest that AV biofeedback has the potential for facilitating reproducible tumor motion towards achieving more accurate medical imaging and radiation therapy procedures.

  12. Sublingual Vaccination Induces Mucosal and Systemic Adaptive Immunity for Protection against Lung Tumor Challenge

    OpenAIRE

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S.; Anthony, Scott M.; Sastry, K. Jagannadha

    2014-01-01

    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge...

  13. Real-time computed tomography fluoroscopy-guided solitary lung tumor model in a rabbit.

    Science.gov (United States)

    Choi, Byeong Hyeon; Young, Hwan Seok; Quan, Yu Hua; Rho, Ji Yun; Eo, Jae Seon; Han, Kook Nam; Choi, Young Ho; Kim, Hyun Koo

    2017-01-01

    Preclinical studies of lung cancer require suitable large-animal models to allow evaluation and development of surgical and interventional techniques. We assessed the feasibility and safety of a novel rabbit lung cancer model of solitary tumors, in which real-time computed tomography fluoroscopy is used to guide inoculation of VX2 carcinoma single-cell suspensions. Thirty-eight rabbits were divided into four groups according to the volume of the VX2 tissue or cell suspension, the volume of lipiodol, the volume of Matrigel, and the injection needle size. The mixtures were percutaneously injected into rabbit lungs under real-time computed tomography fluoroscopy guidance. Two weeks later, VX2 lung carcinomas were confirmed via positron emission tomography/computed tomography, necropsy, and histology. Real-time computed tomography fluoroscopy allowed the precise inoculation of the tumor cell suspensions containing lipiodol, while the use of Matrigel and a small needle prevented leakage of the suspensions into the lung parenchyma. Solitary lung tumors were successfully established in rabbits (n = 22) inoculated with single-cell suspensions (150 μL), lipiodol (150 μL), and Matrigel (150 μL) using a 26-gauge needle. This combination was determined to be optimal. Pneumothorax was observed in only two of the 38 rabbits (5.3%), both of which survived to the end of the study without any intervention. Real-time computed tomography fluoroscopy-guided inoculation of VX2 single-cell suspensions with lipiodol and Matrigel using a small needle is an easy and safe method to establish solitary lung tumors in rabbits.

  14. Feasibility of cell-free circulating tumor DNA testing for lung cancer.

    Science.gov (United States)

    Santarpia, Mariacarmela; Karachaliou, Niki; González-Cao, Maria; Altavilla, Giuseppe; Giovannetti, Elisa; Rosell, Rafael

    2016-01-01

    Tumor tissue genotyping is used routinely for lung cancer to identify specific targetable oncogenic alterations, including EGFR mutations and ALK rearrangements. However, tumor tissue from a single biopsy is often insufficient for molecular testing, may offer a limited evaluation because of tumor heterogeneity and can be difficult to obtain. Cell-free circulating tumor DNA has been widely investigated as a potential surrogate for tissue biopsy for noninvasive assessment of tumor-related genomic alterations. New techniques have improved EGFR mutations detection in ctDNA, thus supporting the use of this liquid biopsy for predicting response to EGFR tyrosine kinase inhibitors (TKIs) and monitoring the emergence of resistance. The serial evaluation of ctDNA during treatment is feasible and can be used to track tumor changes in real time and for a wide range of clinically useful applications.

  15. Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung.

    Science.gov (United States)

    Lugo, Roberto; Gabasa, Marta; Andriani, Francesca; Puig, Marta; Facchinetti, Federica; Ramírez, Josep; Gómez-Caro, Abel; Pastorino, Ugo; Fuster, Gemma; Almendros, Isaac; Gascón, Pere; Davalos, Albert; Reguart, Noemí; Roz, Luca; Alcaraz, Jordi

    2016-12-13

    Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype-specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors.

  16. Tumor Suppressors and Cell-Cycle Proteins in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alfonso Baldi

    2011-01-01

    Full Text Available The cell cycle is the cascade of events that allows a growing cell to duplicate all its components and split into two daughter cells. Cell cycle progression is mediated by the activation of a highly conserved family of protein kinases, the cyclin-dependent kinases (CDKs. CDKs are also regulated by related proteins called cdk inhibitors grouped into two families: the INK4 inhibitors (p16, p15, p19, and p18 and the Cip/Kip inhibitors (p21, p27, and p53. Several studies report the importance of cell-cycle proteins in the pathogenesis and the prognosis of lung cancer. This paper will review the most recent data from the literature about the regulation of cell cycle. Finally, based essentially on the data generated in our laboratory, the expression, the diagnostic, and prognostic significance of cell-cycle molecules in lung cancer will be examined.

  17. Incidentally diagnosed simultaneous second primary tumor of the sphenoid sinus in a patient with lung cancer

    DEFF Research Database (Denmark)

    Yigit, Ozgur; Taskin, Umit; Demir, Ahmet

    2009-01-01

    was made to proceed with chemotherapy and radiotherapy treatment regimens for the sphenoid sinus lesion, and right lobectomy was performed for the lung lesion. Asymptomatic simultaneous, synchronous, or metastatic tumors must always be kept in mind, and histopathologic diagnosis should be done for both...

  18. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, M.M.; Meijer, C.; de Bock, G.H.; Boersma-van Ek, W.; Terstappen, Leonardus Wendelinus Mathias Marie; Groen, H.J.M.; Timens, W.; Kruyt, F.A.E.; Hiltermann, T.N.J.

    2016-01-01

    Background Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and

  19. Circulating tumor cells in small-cell lung cancer : a predictive and prognostic factor

    NARCIS (Netherlands)

    Hiltermann, T J N; Pore, M M; van den Berg, Anke; Timens, W; Boezen, H M; Liesker, J J W; Schouwink, J H; Wijnands, W J A; Kerner, G S M A; Kruyt, F A E; Tissing, H; Tibbe, A G J; Terstappen, L W M M; Groen, H J M

    2012-01-01

    BACKGROUND: Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to

  20. Pulmonary vein tumor thrombosis and left atrial extension in lung carcinoma.

    Science.gov (United States)

    Koo, B C; Woldenberg, L S; Kim, K T

    1984-10-01

    A case of lung carcinoma extending into left atrium through a pulmonary vein and mimicking left atrial myxoma is presented. The localized enlargement of a pulmonary vein is seen as a possible CT sign of pulmonary vein tumor thrombosis. Computed tomography (CT) and echocardiography are complementary in the correct diagnosis of this condition.

  1. Inter-Fraction Tumor Volume Response during Lung Stereotactic Body Radiation Therapy Correlated to Patient Variables.

    Directory of Open Access Journals (Sweden)

    Samer Salamekh

    Full Text Available Analyze inter-fraction volumetric changes of lung tumors treated with stereotactic body radiation therapy (SBRT and determine if the volume changes during treatment can be predicted and thus considered in treatment planning.Kilo-voltage cone-beam CT (kV-CBCT images obtained immediately prior to each fraction were used to monitor inter-fraction volumetric changes of 15 consecutive patients (18 lung nodules treated with lung SBRT at our institution (45-54 Gy in 3-5 fractions in the year of 2011-2012. Spearman's (ρ correlation and Spearman's partial correlation analysis was performed with respect to patient/tumor and treatment characteristics. Multiple hypothesis correction was performed using False Discovery Rate (FDR and q-values were reported.All tumors studied experienced volume change during treatment. Tumor increased in volume by an average of 15% and regressed by an average of 11%. The overall volume increase during treatment is contained within the planning target volume (PTV for all tumors. Larger tumors increased in volume more than smaller tumors during treatment (q = 0.0029. The volume increase on CBCT was correlated to the treatment planning gross target volume (GTV as well as internal target volumes (ITV (q = 0.0085 and q = 0.0039 respectively and could be predicted for tumors with a GTV less than 22 mL. The volume increase was correlated to the integral dose (ID in the ITV at every fraction (q = 0.0049. The peak inter-fraction volume occurred at an earlier fraction in younger patients (q = 0.0122.We introduced a new analysis method to follow inter-fraction tumor volume changes and determined that the observed changes during lung SBRT treatment are correlated to the initial tumor volume, integral dose (ID, and patient age. Furthermore, the volume increase during treatment of tumors less than 22mL can be predicted during treatment planning. The volume increase remained significantly less than the overall PTV expansion, and radiation

  2. Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer

    Directory of Open Access Journals (Sweden)

    Shojaei Farbod

    2012-03-01

    Full Text Available Abstract Osteopontin (OPN, also known as SPP1 (secreted phosphoprotein, is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1. The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6 such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC. CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs. In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor

  3. The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites

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    Ishihara, Makiko; Kobayashi, Hisashi; Ichikawa, Taro; Cho, Keiichi; Gemma, Kazuhito; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan)

    1997-12-01

    CT characteristics of spontaneous rupture of HCC (n=13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary, (e.g., non-hemorrhagic) ascites (n=13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation. (author)

  4. Thermal Ablation of Lung Tumors: Focus on Microwave Ablation.

    Science.gov (United States)

    Vogl, Thomas J; Nour-Eldin, Nour-Eldin A; Albrecht, Moritz Hans; Kaltenbach, Benjamin; Hohenforst-Schmidt, Wolfgang; Lin, Han; Panahi, Bita; Eichler, Kathrin; Gruber-Rouh, Tatjana; Roman, Andrei

    2017-09-01

    Background  Image-guided thermal ablation can be used for the treatment of medically inoperable primary and metastatic lung cancer. These techniques are based on the heating up or freezing (cryoablation) of a volume of tissue around a percutaneous applicator that induces necrosis of the tumor. Method  The English-language literature concerning thermal ablation of the lung was reviewed. Radiofrequency ablation (RFA) is the most widely performed and investigated of these techniques. Microwave ablation (MWA) represents a relatively new alternative that shares the same indications and is conducted in a very similar fashion as RFA. It has been experimentally and clinically shown that MWA produces larger, more spherical ablation zones over shorter periods of time compared to RFA. Seven different MWA systems are available in Europe and the USA with significant differences in the size and shape of the produced ablation zones. Results  The types of complications caused by MWA and their rates of occurrence are very similar to those caused by RFA. The local progression rates after MWA of lung malignancies vary between 0 % and 34 % and are similar to those in the RFA literature. Conclusion  Despite technical improvements, the current generation of MWA systems has comparable clinical outcomes to those of RFA. Key Points   · MWA is a safe technique that should be considered one of the treatment options for medically inoperable lung tumors. · As thermal ablations of lung tumors are becoming more frequent, radiologists should be acquainted with the post-ablation imaging characteristics. · Although MWA has some theoretical advantages over RFA, the clinical outcomes are similar. Citation Format · Vogl TJ, Nour-Eldin NA, Albrecht MH et al. Thermal Ablation of Lung Tumors: Focus on Microwave Ablation. Fortschr Röntgenstr 2017; 189: 828 - 843. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors

    International Nuclear Information System (INIS)

    Nuyttens, Joost J.; Voort van Zyp, Noelle C. van der; Praag, John; Aluwini, Shafak; Klaveren, Rob J. van; Verhoef, Cornelis; Pattynama, Peter M.; Hoogeman, Mischa S.

    2012-01-01

    Purpose: To assess local control, overall survival, and toxicity of four-dimensional, risk-adapted stereotactic body radiotherapy (SBRT) delivered while tracking respiratory motion in patients with primary and metastatic lung cancer located in the central chest. Methods: Fifty-eight central lesions of 56 patients (39 with primary, 17 with metastatic tumors) were treated. Fifteen tumors located near the esophagus were treated with 6 fractions of 8 Gy. Other tumors were treated according to the following dose escalation scheme: 5 fractions of 9 Gy (n = 6), then 5 fractions of 10 Gy (n = 15), and finally 5 fractions of 12 Gy (n = 22). Results: Dose constraints for critical structures were generally achieved; in 21 patients the coverage of the PTV was reduced below 95% to protect adjacent organs at risk. At a median follow-up of 23 months, the actuarial 2-years local tumor control was 85% for tumors treated with a BED >100 Gy compared to 60% for tumors treated with a BED ⩽100 Gy. No grade 4 or 5 toxicity was observed. Acute grade 1–2 esophagitis was observed in 11% of patients. Conclusion: SBRT of central lung lesions can be safely delivered, with promising early tumor control in patients many of whom have severe comorbid conditions.

  6. Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

    International Nuclear Information System (INIS)

    Dano, Laurent

    2000-01-01

    Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

  7. Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

    International Nuclear Information System (INIS)

    Schneider, Katja U; Liebenberg, Volker; Kneip, Christoph; Seegebarth, Anke; Erdogan, Fikret; Rappold, Gudrun; Schmidt, Bernd; Dietrich, Dimo; Fleischhacker, Michael; Leschber, Gunda; Merk, Johannes; Schäper, Frank; Stapert, Henk R; Vossenaar, Erik R; Weickmann, Sabine

    2011-01-01

    DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples

  8. Evaluation of clinical value of combined tumor markers detection in diagnosis of lung cancer

    International Nuclear Information System (INIS)

    Zhang Guangming; Deng Shouzhen; Wang Yun; Xu Lianqin; He Wanting; Gao Quan; Lin Xiangtong

    2002-01-01

    To evaluate clinical value of single or combined tumor marker detection CY21-1, CEA, CA15-3 and SCC in the diagnosis of lung cancer. There was retrospective analysis of 87 lung cancer inpatients, all of them was confirmed by pathology. Results showed: (1) Sensitivity of CY21-1, CEA, CA15-3 and SCC by single detection in diagnosing lung cancer was 59.8%, 39.1%, 44.8%, 18.4%, respectively. (2) Sensitivity of group I (CY21-1 + CEA) was 78.2%; sensitivity of group II (CY21-1 + CEA + CA15-3) was 88.5%; sensitivity of group III (CY21-1 + CEA + CA15-3 + SCC) was the same as group II. In the diagnosis of lung cancer, the combined detection with CY21-1, CEA, CA15-3 was an ideal selective combination

  9. Mitigation of motion artifacts in CBCT of lung tumors based on tracked tumor motion during CBCT acquisition

    International Nuclear Information System (INIS)

    Lewis, John H; Li Ruijiang; Jia Xun; Watkins, W Tyler; Song, William Y; Jiang, Steve B; Lou, Yifei

    2011-01-01

    An algorithm capable of mitigating respiratory motion blurring artifacts in cone-beam computed tomography (CBCT) lung tumor images based on the motion of the tumor during the CBCT scan is developed. The tumor motion trajectory and probability density function (PDF) are reconstructed from the acquired CBCT projection images using a recently developed algorithm Lewis et al (2010 Phys. Med. Biol. 55 2505-22). Assuming that the effects of motion blurring can be represented by convolution of the static lung (or tumor) anatomy with the motion PDF, a cost function is defined, consisting of a data fidelity term and a total variation regularization term. Deconvolution is performed through iterative minimization of this cost function. The algorithm was tested on digital respiratory phantom, physical respiratory phantom and patient data. A clear qualitative improvement is evident in the deblurred images as compared to the motion-blurred images for all cases. Line profiles show that the tumor boundaries are more accurately and clearly represented in the deblurred images. The normalized root-mean-squared error between the images used as ground truth and the motion-blurred images are 0.29, 0.12 and 0.30 in the digital phantom, physical phantom and patient data, respectively. Deblurring reduces the corresponding values to 0.13, 0.07 and 0.19. Application of a -700 HU threshold to the digital phantom results in tumor dimension measurements along the superior-inferior axis of 2.8, 1.8 and 1.9 cm in the motion-blurred, ground truth and deblurred images, respectively. Corresponding values for the physical phantom are 3.4, 2.7 and 2.7 cm. A threshold of -500 HU applied to the patient case gives measurements of 3.1, 1.6 and 1.7 cm along the SI axis in the CBCT, 4DCT and deblurred images, respectively. This technique could provide more accurate information about a lung tumor's size and shape on the day of treatment.

  10. Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET

    International Nuclear Information System (INIS)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2008-01-01

    Small animal positron emission tomography (PET) with 18 F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal 18 F-FDG PET. Methods: To determine the impact of anesthesia on 18 F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of 18 F-FDG in various tissues were evaluated. The 18 F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of 18 F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased 18 F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest 18 F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by 18 F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal 18 F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire 18 F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model

  11. FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

    Science.gov (United States)

    He, Lingfeng; Luo, Libo; Zhu, Hong; Yang, Huan; Zhang, Yilan; Wu, Huan; Sun, Hongfang; Jiang, Feng; Kathera, Chandra S; Liu, Lingjie; Zhuang, Ziheng; Chen, Haoyan; Pan, Feiyan; Hu, Zhigang; Zhang, Jing; Guo, Zhigang

    2017-06-01

    Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small-molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage-inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor-targeting therapy for lung cancer. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  12. Dosimetric effect of intrafraction tumor motion in phase gated lung stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Zhao Bo; Yang Yong; Li Tianfang; Li Xiang; Heron, Dwight E.; Huq, M. Saiful

    2012-01-01

    Purpose: A major concern for lung intensity modulated radiation therapy delivery is the deviation of actually delivered dose distribution from the planned one due to simultaneous movements of multileaf collimator (MLC) leaves and tumor. For gated lung stereotactic body radiotherapy treatment (SBRT), the situation becomes even more complicated because of SBRT's characteristics such as fewer fractions, smaller target volume, higher dose rate, and extended fractional treatment time. The purpose of this work is to investigate the dosimetric effect of intrafraction tumor motion during gated lung SBRT delivery by reconstructing the delivered dose distribution with real-time tumor motion considered. Methods: The tumor motion data were retrieved from six lung patients. Each of them received three fractions of stereotactic radiotherapy treatments with Cyberknife Synchrony (Accuray, Sunnyvale, CA). Phase gating through an external surrogate was simulated with a gating window of 5 mm. The resulting residual tumor motion curves during gating (beam-on) were retrieved. Planning target volume (PTV) was defined as physician-contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin. Each patient was prescribed with 60 Gy/3 fractions. The authors developed an algorithm to reconstruct the delivered dose with tumor motion. The DMLC segments, mainly leaf position and segment weighting factor, were recalculated according to the probability density function of tumor motion curve. The new DMLC sequence file was imported back to treatment planning system to reconstruct the dose distribution. Results: Half of the patients in the study group experienced PTV D95% deviation up to 26% for fractional dose and 14% for total dose. CTV mean dose dropped by 1% with tumor motion. Although CTV is almost covered by prescribed dose with 5 mm margin, qualitative comparison on the dose distributions reveals that CTV is on the verge of underdose. The discrepancy happens due to tumor

  13. Dosimetric analysis of rib interference of the CTV during interstitial brachytherapy of lung tumors.

    Science.gov (United States)

    Yang, Bo; Sun, Xiaoyang; Pang, Haowen; Shi, Xiangxiang; Tang, Tao; Zhang, Guangpeng; Chen, Renjin; Zhang, Jing; Wu, Hong; Lin, Sheng; Wen, Qinglian; Han, Yunwei; Wu, Jingbo

    2017-12-01

    In interstitial brachytherapy for lung tumors, the placement and alignment of the source needles are influenced by the ribs, which can affect the dose distribution. This study evaluated the change in dose to the target by comparing the dose between the actual interstitial brachytherapy plan (AIBP, what is deliverable due to anatomic constraints), and the virtual interstitial brachytherapy plan (VIBP, pretreatment-modified dose distribution). AIBPs and VIBPs were designed for 20 lung tumors. The VIBP was designed with uniform spacing between needles, regardless of the presence of ribs. The prescription dose was 30 Gy. The percentage of normal ipsilateral lung volume that received a dose ≥ 5 Gy (V 5 ), conformity index (COIN), incremental dose percentage (IDP) to the target, and the dose covering 95% (D 95 ) of the clinical target volume (CTV) were calculated. The V 5 of the VIBPs was significantly smaller than that of the AIBPs ( p 0.05). The regular geometric alignment of needles is important for increasing the target dose and limiting the normal lung dose in interstitial brachytherapy for thoracic tumors. Thus, we recommend that radiation oncologists attempt to achieve the regular alignment of needles during implantation.

  14. Dosimetric analysis of rib interference of the CTV during interstitial brachytherapy of lung tumors

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    Bo Yang

    2017-12-01

    Full Text Available Purpose : In interstitial brachytherapy for lung tumors, the placement and alignment of the source needles are influenced by the ribs, which can affect the dose distribution. This study evaluated the change in dose to the target by comparing the dose between the actual interstitial brachytherapy plan (AIBP, what is deliverable due to anatomic constraints, and the virtual interstitial brachytherapy plan (VIBP, pretreatment-modified dose distribution. Material and methods : AIBPs and VIBPs were designed for 20 lung tumors. The VIBP was designed with uniform spacing between needles, regardless of the presence of ribs. The prescription dose was 30 Gy. The percentage of normal ipsilateral lung volume that received a dose ≥ 5 Gy (V 5 , conformity index (COIN, incremental dose percentage (IDP to the target, and the dose covering 95% (D 95 of the clinical target volume (CTV were calculated. Results : The V 5 of the VIBPs was significantly smaller than that of the AIBPs (p 0.05. Conclusions : The regular geometric alignment of needles is important for increasing the target dose and limiting the normal lung dose in interstitial brachytherapy for thoracic tumors. Thus, we recommend that radiation oncologists attempt to achieve the regular alignment of needles during implantation.

  15. Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer.

    Science.gov (United States)

    Yi, Fuming; Amarasinghe, Baru; Dang, Thao P

    2013-01-01

    Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch's response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.

  16. Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

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    Rong Wang

    2013-01-01

    Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

  17. β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

    Science.gov (United States)

    Yu, Xiaomu; Xu, Maoyi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

    2017-08-19

    Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Histogenesis of lung tumors induced in rats by inhalation of α emitters. An overview

    International Nuclear Information System (INIS)

    Masse, R.

    1979-01-01

    Recent reviews have shown that simular risks coefficients for α irradiation of the lung in man could be deduced using epidemiological or experimental data in animals. Most experimental data were obtained in rats. In this overview the histogenesis and ultrastructure of lung tumors are presented. Only few tumors originating from lung parenchyma could be considered as non relevant for extrapolation to man. Most tumors arose from axial bronchus or bronchioles and their histogenesis was very similar to what is known in man. The only striking difference between the two species was related to the growth characteristics of the tumors. Tumors in rat, frequently papillary, acquired only slowly their full malignancy. They seem to be only potentially malignant. Two main types of tumors were considered: bronchogenic (B) and bronchiolo alveolar (b.a.) carcinomas. Survivals of the cancerous rats were log normal distribution in a given group of dose and were supposed to reflect latent period. No difference was found between B and b.a. carcinomas; geometric standard deviation did not increase when doses decrease. Since risk coefficients were found to increase when dose decreased, and through latent period fitted well with a power function of dose within the dose range studied, it is observed that the latent period can not be deduced by extrapolation at low doses. b.a. carcinomas prevailed at low doses; the relevance of this observation to man is however dubious since combined action with environmental carcinogens led to a high prevalence of B. carcinomas. Though genetic and immune surveillance are factors of some importance in the determination of the tumors it is suggested that critical individuals will be mostly multi-exposed individuals

  19. Spontaneous transformation of murine oviductal epithelial cells: A model system to investigate the onset of fallopian-derived tumors

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    MIchael P. Endsley

    2015-07-01

    Full Text Available High-grade serous carcinoma (HGSC is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described. Apart from a subpopulation of genetically predisposed women, most women develop ovarian cancer spontaneously, which is associated with aging and lifetime ovulations. A murine oviductal cell line (MOELOW was developed and continuously passaged in culture to mimic cellular aging (MOEHIGH. The MOEHIGH cellular model exhibited a loss of acetylated tubulin consistent with an outgrowth of secretory epithelial cells in culture. MOEHIGH cells proliferated significantly faster than MOELOW, and the MOEHIGH cells produced more 2D foci and 3D soft agar colonies as compared to MOELOW. MOEHIGH were xenografted into athymic female nude mice both in the subcutaneous and the intraperiteonal compartments. Only the subcutaneous grafts formed tumors that were negative for cytokeratin, but positive for oviductal markers such as oviductal glycoprotein 1 and Pax8. These tumors were considered to be poorly differentiated carcinoma. The differential molecular profiles between MOEHIGH and MOELOW were determined using RNA-Seq and confirmed by protein expression to uncover pathways important in transformation, like the p53 pathway, the FOXM1 pathway, WNT signaling, and splicing. MOEHIGH had enhanced protein expression of c-myc, Cyclin E, p53 and FOXM1 with reduced expression of p21. MOEHIGH were also less sensitive to cisplatin and DMBA, which induce lesions typically repaired by base-excision repair. A model of spontaneous tumorogenesis was generated starting with normal oviductal cells. Their transition to cancer involved alterations in pathways associated with high-grade serous cancer in humans.

  20. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice.

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    Alison K Bauer

    Full Text Available Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+ and Nrf2(-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/- mice compared to Nrf2(+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/- mice than in Nrf2(+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+ mice relative to Nrf2(-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy.

  1. A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

    Directory of Open Access Journals (Sweden)

    Foroulis Christophoros N

    2008-12-01

    Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

  2. Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

    Science.gov (United States)

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

    2016-03-01

    The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

  3. In vitro and in vivo evaluation of combined calcitriol and cisplatin in dogs with spontaneously occurring tumors

    Science.gov (United States)

    Rassnick, Kenneth M.; Muindi, Josephia R.; Johnson, Candace S.; Balkman, Cheryl E.; Ramnath, Nithya; Yu, Wei-Dong; Engler, Kristie L.; Page, Rodney L.; Trump, Donald L.

    2009-01-01

    Purpose Calcitriol potentiates cisplatin-mediated activity in a variety of tumor models. We examine here, the effect of calcitriol and cisplatin pre-clinically and clinically in canine spontaneous tumors through in vitro studies on tumor cells and through a phase I study of calcitriol and cisplatin to identify the maximum-tolerated dosage (MTD) of this combination in dogs with cancer and to characterize the pharmacokinetic disposition of calcitriol in dogs. Methods Canine tumor cells were investigated for calcitriol/cisplatin interactions on proliferation using an MTT assay in a median-dose effect analysis; data were used to derive a combination index (CI). Cisplatin was given at a fixed dosage of 60 mg/m2. Calcitriol was given i.v. and the dosage was escalated in cohorts of three dogs until the MTD was defined. Serum calcitriol concentrations were quantified by radioimmunoassay. Results In vitro, CIs1.5 μg/kg achieved Cmax ≥ 9.8 ng/mL and dosages >1.0 μg/kg achieved AUC ≥ 45 h ng/mL. Conclusions Calcitriol and cisplatin have synergistic antiproliferative effects on multiple canine tumor cells and high-dosages of i.v. calcitriol in combination with cisplatin can be safely administered to dogs. Cmax and AUC at the MTD 3.75 μg/kg calcitriol exceed concentrations associated with antitumor activity in a murine model, indicating this combination might have significant clinical utility in dogs. PMID:18246349

  4. fDOT for in vivo follow-up of tumor development in mice lungs

    Science.gov (United States)

    Koenig, Anne; Hervé, Lionel; Da Silva, Anabela; Dinten, Jean-Marc; Boutet, Jérôme; Berger, Michel; Josserand, Véronique; Coll, Jean-Luc; Peltié, Philippe; Rizo, Philippe

    2007-07-01

    This paper presents in vivo experiments conducted on cancerous mice bearing mammary murine tumors. In order to reconstruct the fluorescence yield even in highly attenuating and heterogeneous regions like lungs, we developed a fDOT reconstruction method which at first corrects the light propagation model from optical heterogeneities by using the transmitted excitation light measurements. The same approach is also designed to enable working without immersing the mouse in adaptation liquid. The 3D fluorescence map is then reconstructed from the emitted signal of fluorescence and from the corrected propagation model by an ART (Algebraic Reconstruction Technique) algorithm. The system ability to reconstruct fluorescence distribution in presence of high attenuating objects has been validated on phantoms presenting a fluorescent absorbent inclusion. A study was conducted on mice to follow up lungs at different stages of tumor development. The mice were imaged after intravenous injection to the animal of a cancer specific fluorescent marker. A control experiment was conducted in parallel on healthy mice to ensure that the multiple injections of fluorophore did not induce parasite fluorescence distribution. These results validate our system performances for studying small animal lungs tumor evolution. Detection and localization of the fluorophore fixations expresses the tumor development.

  5. Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report.

    Science.gov (United States)

    Gunji-Niitsu, Yoko; Kumasaka, Toshio; Kitamura, Shigehiro; Hoshika, Yoshito; Hayashi, Takuo; Tokuda, Hitoshi; Morita, Riichiro; Kobayashi, Etsuko; Mitani, Keiko; Kikkawa, Mika; Takahashi, Kazuhisa; Seyama, Kuniaki

    2016-11-21

    Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2

  6. Gastrointestinal stromal tumor masquerading as a lung neoplasm. A case presentation and literature review

    Directory of Open Access Journals (Sweden)

    Papagiannopoulos K

    2008-05-01

    Full Text Available Abstract Gastrointestinal stromal tumors (GISTs are rare neoplasms of the gastrointestinal tract. Their incidence in the esophagus is 1%–3%. Never has a GIST been documented to directly invade the lung. We report a primary esophageal GIST with direct invasion into the lung parenchyma, presenting predominantly with respiratory symptoms. We include a retrospective literature review. Although the principle 'common things are common' usually guides our everyday clinical practice, this case emphasizes that rare entities can mimic common pathologies and underlines the importance of having a clearly defined differential diagnostic list which should be meticulously scrutinized.

  7. An accurate algorithm to match imperfectly matched images for lung tumor detection without markers.

    Science.gov (United States)

    Rozario, Timothy; Bereg, Sergey; Yan, Yulong; Chiu, Tsuicheng; Liu, Honghuan; Kearney, Vasant; Jiang, Lan; Mao, Weihua

    2015-05-08

    In order to locate lung tumors on kV projection images without internal markers, digitally reconstructed radiographs (DRRs) are created and compared with projection images. However, lung tumors always move due to respiration and their locations change on projection images while they are static on DRRs. In addition, global image intensity discrepancies exist between DRRs and projections due to their different image orientations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported to match imperfectly matched projection images and DRRs. The kV projection images were matched with different DRRs in two steps. Preprocessing was performed in advance to generate two sets of DRRs. The tumors were removed from the planning 3D CT for a single phase of planning 4D CT images using planning contours of tumors. DRRs of background and DRRs of tumors were generated separately for every projection angle. The first step was to match projection images with DRRs of background signals. This method divided global images into a matrix of small tiles and similarities were evaluated by calculating normalized cross-correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) was automatically optimized to keep the tumor within a single projection tile that had a bad matching with the corresponding DRR tile. A pixel-based linear transformation was determined by linear interpolations of tile transformation results obtained during tile matching. The background DRRs were transformed to the projection image level and subtracted from it. The resulting subtracted image now contained only the tumor. The second step was to register DRRs of tumors to the subtracted image to locate the tumor. This method was successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (BrainLAB) for dynamic tumor tracking on phantom studies. Radiation opaque markers were

  8. Tumor Localization Using Cone-Beam CT Reduces Setup Margins in Conventionally Fractionated Radiotherapy for Lung Tumors

    International Nuclear Information System (INIS)

    Yeung, Anamaria R.; Li, Jonathan G.; Shi Wenyin; Newlin, Heather E.; Chvetsov, Alexei; Liu, Chihray; Palta, Jatinder R.; Olivier, Kenneth

    2009-01-01

    Purpose: To determine whether setup margins can be reduced using cone-beam computed tomography (CBCT) to localize tumor in conventionally fractionated radiotherapy for lung tumors. Methods and Materials: A total of 22 lung cancer patients were treated with curative intent with conventionally fractionated radiotherapy using daily image guidance with CBCT. Of these, 13 lung cancer patients had sufficient CBCT scans for analysis (389 CBCT scans). The patients underwent treatment simulation in the BodyFix immobilization system using four-dimensional CT to account for respiratory motion. Daily alignment was first done according to skin tattoos, followed by CBCT. All 389 CBCT scans were retrospectively registered to the planning CT scans using automated soft-tissue and bony registration; the resulting couch shifts in three dimensions were recorded. Results: The daily alignment to skin tattoos with no image guidance resulted in systematic (Σ) and random (σ) errors of 3.2-5.6 mm and 2.0-3.5 mm, respectively. The margin required to account for the setup error introduced by aligning to skin tattoos with no image guidance was approximately 1-1.6 cm. The difference in the couch shifts obtained from the bone and soft-tissue registration resulted in systematic (Σ) and random (σ) errors of 1.5-4.1 mm and 1.8-5.3 mm, respectively. The margin required to account for the setup error introduced using bony anatomy as a surrogate for the target, instead of localizing the target itself, was 0.5-1.4 cm. Conclusion: Using daily CBCT soft-tissue registration to localize the tumor in conventionally fractionated radiotherapy reduced the required setup margin by up to approximately 1.5 cm compared with both no image guidance and image guidance using bony anatomy as a surrogate for the target.

  9. Topology polymorphism graph for lung tumor segmentation in PET-CT images

    Science.gov (United States)

    Cui, Hui; Wang, Xiuying; Zhou, Jianlong; Eberl, Stefan; Yin, Yong; Feng, Dagan; Fulham, Michael

    2015-06-01

    Accurate lung tumor segmentation is problematic when the tumor boundary or edge, which reflects the advancing edge of the tumor, is difficult to discern on chest CT or PET. We propose a ‘topo-poly’ graph model to improve identification of the tumor extent. Our model incorporates an intensity graph and a topology graph. The intensity graph provides the joint PET-CT foreground similarity to differentiate the tumor from surrounding tissues. The topology graph is defined on the basis of contour tree to reflect the inclusion and exclusion relationship of regions. By taking into account different topology relations, the edges in our model exhibit topological polymorphism. These polymorphic edges in turn affect the energy cost when crossing different topology regions under a random walk framework, and hence contribute to appropriate tumor delineation. We validated our method on 40 patients with non-small cell lung cancer where the tumors were manually delineated by a clinical expert. The studies were separated into an ‘isolated’ group (n = 20) where the lung tumor was located in the lung parenchyma and away from associated structures / tissues in the thorax and a ‘complex’ group (n = 20) where the tumor abutted / involved a variety of adjacent structures and had heterogeneous FDG uptake. The methods were validated using Dice’s similarity coefficient (DSC) to measure the spatial volume overlap and Hausdorff distance (HD) to compare shape similarity calculated as the maximum surface distance between the segmentation results and the manual delineations. Our method achieved an average DSC of 0.881  ±  0.046 and HD of 5.311  ±  3.022 mm for the isolated cases and DSC of 0.870  ±  0.038 and HD of 9.370  ±  3.169 mm for the complex cases. Student’s t-test showed that our model outperformed the other methods (p-values <0.05).

  10. Dermatomyositis as the first manifestation of a lung tumor

    Directory of Open Access Journals (Sweden)

    A. Castro

    2013-07-01

    Full Text Available Dermatomyositis (DM is a rare disease characterized by proximal muscle weakness and a typical cutaneous rash. The muscle biopsy shows inflammatory lesions consistent with myositis, being related to an increased risk of cancer, often being considered as a paraneoplastic syndrome. The authors present a case of a 63-year-old man, with progressive proximal muscle weakness and cutaneous rash, appearing in two months. The muscle and skin biopsies were consistent with DM. Chest tomography showed that a nodular image in the lingular region and bronchy biopsy confirmed the diagnosis of small cell lung carcinoma (SCLC. This clinical case intends to enhance the importance of a thorough diagnostic study in patients with DM, as it is often a paraneoplastic syndrome. Resumo: A dermatomiosite (DM é uma doença rara, caracterizada por fraqueza muscular proximal associada a exantema cutâneo típico. A biopsia muscular apresenta lesões inflamatórias compatíveis com miosite, estando associada a um aumento de risco de neoplasia, frequentemente considerada como síndrome paraneoplásico. Os autores apresentam um caso de um homem de 63 anos, com quadro de fraqueza muscular proximal progressiva e exantema cutâneo com 2 meses de evolução. A biopsia cutânea e muscular foram compatíveis com DM. A tomografia tórax mostrou imagem nodular paracardíaca esquerda e a biopsia brônquica confirmou diagnóstico de carcinoma pulmão pequenas células. Este caso clínico pretende realçar a importância da realização do estudo diagnóstico exaustivo em doentes com DM, visto que esta patologia surge frequentemente como síndrome paraneoplásico. Keywords: Dermatomyositis, Lung neoplasms, Paraneoplastic syndrome, Palavras-chave: Dermatomiosite, Neoplasias pulmonares, Síndrome paraneoplásico

  11. Large malignant phyllodes tumor of the breast with metastases to the lungs

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-05-01

    Full Text Available Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies.

  12. Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

    Directory of Open Access Journals (Sweden)

    Rodríguez-Padilla Cristina

    2011-09-01

    Full Text Available Abstract Background Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like env gene sequences. Results The MMTV-like env gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the env sequences exhibited disruption of the reading frame due to mutations. Conclusion In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18% of the lung carcinomas and 1 out of 7 (14% of acute inflamatory lung infiltrate specimens studied of a Mexican Population.

  13. Effects of high fat diet on incidence of spontaneous tumors in Wistar rats

    DEFF Research Database (Denmark)

    KRISTIANSEN, E.; Madsen, Charlotte Bernhard; Meyer, Otto A.

    1993-01-01

    . There was no difference in food consumption, body weight, weight gain, and longevity between the two groups. A statistically significant increase in the incidence of tumors in the high-fat group was seen in fibroadenoma of the mammae (female, p = 0.05). No statistically significant difference was seen when the incidence...... of benign mammary tumors (adenomas and fibroadenomas) was combined, just as the overall incidence of mammary tumors (adenomas, fibroadenomas, and adenocarcinomas) was not significantly different between the groups. A statistically significant decrease in the incidence of tumors in the high-fat group...

  14. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity.

    Science.gov (United States)

    Saunders, Sean P; Moran, Tara; Floudas, Achilleas; Wurlod, Felicity; Kaszlikowska, Agnieszka; Salimi, Maryam; Quinn, Emma M; Oliphant, Christopher J; Núñez, Gabriel; McManus, Ross; Hams, Emily; Irvine, Alan D; McKenzie, Andrew N J; Ogg, Graham S; Fallon, Padraic G

    2016-02-01

    Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development in a phenomenon known as the atopic march. Although genetic and environmental factors are known to contribute to AD and asthma, the mechanisms underlying the atopic march remain poorly understood. Filaggrin loss-of-function mutations are a major genetic predisposer for the development of AD and progression to AD-associated asthma. We sought to experimentally address whether filaggrin mutations in mice lead to the development of spontaneous eczematous inflammation and address the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency. Filaggrin mutant mice were generated on the proallergic BALB/c background, creating a novel model for the assessment of spontaneous AD-like inflammation. Independently recruited AD case collections were analyzed to define associations between filaggrin mutations and immunologic phenotypes. Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like inflammation with progression to compromised pulmonary function with age, reflecting the atopic march in patients with AD. Strikingly, skin inflammation occurs independently of adaptive immunity and is associated with cutaneous expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects with filaggrin mutations have an increased frequency of type 2 innate lymphoid cells in the skin in comparison with control subjects. This study provides new insights into our understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

    Science.gov (United States)

    Liu, Shangang; Ren, Ruimei; Liu, Ming; Lv, Yubo; Li, Bin; Li, Chengli

    2014-09-01

    To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

  16. Alterations in the K-ras and p53 genes in rat lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Swafford, D.S.; Finch, G.L.; Mitchell, C.E. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)] [and others

    1997-06-01

    Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. The transition mutations formed could have been derived from deamination of cytosine. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 of 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors. 2 figs., 2 tabs., 48 refs.

  17. Automated measurements of metabolic tumor volume and metabolic parameters in lung PET/CT imaging

    Science.gov (United States)

    Orologas, F.; Saitis, P.; Kallergi, M.

    2017-11-01

    Patients with lung tumors or inflammatory lung disease could greatly benefit in terms of treatment and follow-up by PET/CT quantitative imaging, namely measurements of metabolic tumor volume (MTV), standardized uptake values (SUVs) and total lesion glycolysis (TLG). The purpose of this study was the development of an unsupervised or partially supervised algorithm using standard image processing tools for measuring MTV, SUV, and TLG from lung PET/CT scans. Automated metabolic lesion volume and metabolic parameter measurements were achieved through a 5 step algorithm: (i) The segmentation of the lung areas on the CT slices, (ii) the registration of the CT segmented lung regions on the PET images to define the anatomical boundaries of the lungs on the functional data, (iii) the segmentation of the regions of interest (ROIs) on the PET images based on adaptive thresholding and clinical criteria, (iv) the estimation of the number of pixels and pixel intensities in the PET slices of the segmented ROIs, (v) the estimation of MTV, SUVs, and TLG from the previous step and DICOM header data. Whole body PET/CT scans of patients with sarcoidosis were used for training and testing the algorithm. Lung area segmentation on the CT slices was better achieved with semi-supervised techniques that reduced false positive detections significantly. Lung segmentation results agreed with the lung volumes published in the literature while the agreement between experts and algorithm in the segmentation of the lesions was around 88%. Segmentation results depended on the image resolution selected for processing. The clinical parameters, SUV (either mean or max or peak) and TLG estimated by the segmented ROIs and DICOM header data provided a way to correlate imaging data to clinical and demographic data. In conclusion, automated MTV, SUV, and TLG measurements offer powerful analysis tools in PET/CT imaging of the lungs. Custom-made algorithms are often a better approach than the manufacturer

  18. A statistical method for lung tumor segmentation uncertainty in PET images based on user inference.

    Science.gov (United States)

    Zheng, Chaojie; Wang, Xiuying; Feng, Dagan

    2015-01-01

    PET has been widely accepted as an effective imaging modality for lung tumor diagnosis and treatment. However, standard criteria for delineating tumor boundary from PET are yet to develop largely due to relatively low quality of PET images, uncertain tumor boundary definition, and variety of tumor characteristics. In this paper, we propose a statistical solution to segmentation uncertainty on the basis of user inference. We firstly define the uncertainty segmentation band on the basis of segmentation probability map constructed from Random Walks (RW) algorithm; and then based on the extracted features of the user inference, we use Principle Component Analysis (PCA) to formulate the statistical model for labeling the uncertainty band. We validated our method on 10 lung PET-CT phantom studies from the public RIDER collections [1] and 16 clinical PET studies where tumors were manually delineated by two experienced radiologists. The methods were validated using Dice similarity coefficient (DSC) to measure the spatial volume overlap. Our method achieved an average DSC of 0.878 ± 0.078 on phantom studies and 0.835 ± 0.039 on clinical studies.

  19. Long-term local control with radiofrequency ablation or radiotherapy for second, third, and fourth lung tumors after lobectomy for primary lung cancer

    International Nuclear Information System (INIS)

    Yokouchi, Hideoki; Murata, Kohei; Miyazaki, Masaki; Miyamoto, Takeaki; Minami, Takafumi; Tsuji, Fumio; Mikami, Koji

    2016-01-01

    A 78-year-old woman developed second, third, and fourth lung tumors at intervals of 1-3 years after left upper lobectomy for primary lung cancer. The tumors were controlled with radiofrequency ablation (RFA) or conventional conformal radiotherapy for 9 years postoperatively. For the treatment of second primary lung cancer or lung metastasis after surgical resection of the primary lung cancer, reoperation is not recommended because of the impaired respiratory reserve. Thus, local therapy such as radiotherapy or RFA is applied in some cases. Among these, stereotactic body radiotherapy (SBRT) is a feasible option because of its good local control and safety, which is comparable with surgery. On the other hand, for cases of multiple lesions that are not suitable for radiotherapy or combination therapy, RFA could be an option because of its short-term local control, easiness, safety, and repeatability. After surgery for primary lung cancer, a second lung tumor could be controlled with highly effective and minimally invasive local therapy if it is recognized as a local disease but is medically inoperable. Therefore, long-term postoperative follow-up for primary lung cancer is beneficial. (author)

  20. A Novel Markerless Technique to Evaluate Daily Lung Tumor Motion Based on Conventional Cone-Beam CT Projection Data

    International Nuclear Information System (INIS)

    Yang Yin; Zhong Zichun; Guo Xiaohu; Wang Jing; Anderson, John; Solberg, Timothy; Mao Weihua

    2012-01-01

    Purpose: In this study, we present a novel markerless technique, based on cone beam computed tomography (CBCT) raw projection data, to evaluate lung tumor daily motion. Method and Materials: The markerless technique, which uses raw CBCT projection data and locates tumors directly on every projection, consists of three steps. First, the tumor contour on the planning CT is used to create digitally reconstructed radiographs (DRRs) at every projection angle. Two sets of DRRs are created: one showing only the tumor, and another with the complete anatomy without the tumor. Second, a rigid two-dimensional image registration is performed to register the DRR set without the tumor to the CBCT projections. After the registration, the projections are subtracted from the DRRs, resulting in a projection dataset containing primarily tumor. Finally, a second registration is performed between the subtracted projection and tumor-only DRR. The methodology was evaluated using a chest phantom containing a moving tumor, and retrospectively in 4 lung cancer patients treated by stereotactic body radiation therapy. Tumors detected on projection images were compared with those from three-dimensional (3D) and four-dimensional (4D) CBCT reconstruction results. Results: Results in both static and moving phantoms demonstrate that the accuracy is within 1 mm. The subsequent application to 22 sets of CBCT scan raw projection data of 4 lung cancer patients includes about 11,000 projections, with the detected tumor locations consistent with 3D and 4D CBCT reconstruction results. This technique reveals detailed lung tumor motion and provides additional information than conventional 4D images. Conclusion: This technique is capable of accurately characterizing lung tumor motion on a daily basis based on a conventional CBCT scan. It provides daily verification of the tumor motion to ensure that these motions are within prior estimation and covered by the treatment planning volume.

  1. Detecting small lung tumors in mouse models by refractive-index microradiology

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Chia-Chi; Hwu, Y. [Academia Sinica, Institute of Physics, Taipei (China); National Tsing Hua University, Department of Engineering and System Science, Hsinchu (China); Zhang, Guilin; Yue, Weisheng; Li, Yan; Xue, Hongjie [Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai (China); Liu, Ping; Sun, Jianqi; Xu, Lisa X. [Shanghai Jiao Tong University, Shanghai (China); Wang, Chang Hai; Chen, Nanyow; Lu, Chien Hung; Lee, Ting-Kuo [Academia Sinica, Institute of Physics, Taipei (China); Yang, Yuh-Cheng; Lu, Yen-Ta [Mackay Memorial Hospital, Taipei City (China); Ching, Yu-Tai [National Chiao Tung University, Department of Computer Science, Hsinchu (China); Shih, T.F.; Yang, P.C. [National Taiwan University, College of Medicine, Taipei (China); Je, J.H. [Pohang University of Science and Technology Pohang, X-ray Imaging Center, Pohang CT, Kyungbuk (Korea, Republic of); Margaritondo, G. [Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland)

    2011-08-15

    Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm{sup 3} with accuracy better than 1 x 10{sup -3} mm{sup 3}. This level of performance is currently suitable for animal studies, while further developments are required for clinical application. (orig.)

  2. 4π Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors

    International Nuclear Information System (INIS)

    Dong, Peng; Lee, Percy; Ruan, Dan; Long, Troy; Romeijn, Edwin; Low, Daniel A.; Kupelian, Patrick; Abraham, John; Yang, Yingli; Sheng, Ke

    2013-01-01

    Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. Results: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R 50 was reduced by more than 50%. Lung V 20 , V 10 , and V 5 were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and

  3. Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases

    International Nuclear Information System (INIS)

    Boda-Heggemann, Judit; Wenz, Frederik; Lohr, Frank; Frauenfeld, Anian; Weiss, Christel; Simeonova, Anna; Neumaier, Christian; Siebenlist, Kerstin; Attenberger, Ulrike; Heußel, Claus Peter; Schneider, Frank

    2014-01-01

    Stereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED). 50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed. The median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%. Intensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control

  4. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    OpenAIRE

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluoresce...

  5. Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic.

    Science.gov (United States)

    Nelson, Gail M; Ahlborn, Gene J; Allen, James W; Ren, Hongzu; Corton, J Christopher; Waalkes, Michael P; Kitchin, Kirk T; Diwan, Bhalchandra A; Knapp, Geremy; Delker, Don A

    2009-12-21

    Exposure of male C3H mice in utero (from gestational days 8-18) to 85ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.

  6. Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic

    International Nuclear Information System (INIS)

    Nelson, Gail M.; Ahlborn, Gene J.; Allen, James W.; Ren, Hongzu; Corton, J. Christopher; Waalkes, Michael P.; Kitchin, Kirk T.; Diwan, Bhalchandra A.; Knapp, Geremy; Delker, Don A.

    2009-01-01

    Exposure of male C3H mice in utero (from gestational days 8-18) to 85 ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85 ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.

  7. The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer

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    Wei-Lun Huang

    2015-01-01

    Full Text Available The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR. The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer.

  8. Capturing Genomic Evolution of Lung Cancers through Liquid Biopsy for Circulating Tumor DNA

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    Michael Offin

    2017-01-01

    Full Text Available Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor’s dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure. The ability to analyze ctDNA from plasma, CSF, or urine enables a comprehensive view of cancers as systemic diseases and captures intratumoral heterogeneity. Here, we describe these recent advances in the setting of lung cancers and advocate for further research and the incorporation of ctDNA analysis in clinical trials of targeted therapies. By capturing genomic evolution in a noninvasive manner, liquid biopsy for ctDNA analysis could accelerate therapeutic discovery and deliver the next leap forward in precision medicine for patients with lung cancers and other solid tumors.

  9. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Olya Grove

    Full Text Available Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity and intratumor density variation (feature 2: entropy ratio in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47 of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92. Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04 in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8. In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.

  10. Dose impact of a carbon fiber couch for stereotactic body radiation therapy of lung tumors

    International Nuclear Information System (INIS)

    Tominaga, Hirofumi; Kanetake, Nagisa; Kawasaki, Keiichi; Iwashita, Yuki; Sakata, Junichi; Okuda, Tomoko; Araki, Fujio; Shimohigashi, Yoshinobu; Tomiyama, Yuki

    2013-01-01

    The aim of this study was to measure the dose attenuation caused by a carbon fiber radiation therapy table (Imaging Couch Top; ICT, BrainLab) and to evaluate the dosimetric impact of ICT during stereotactic body radiation therapy (SBRT) in lung tumors. The dose attenuation of ICT was measured using an ionization chamber and modeled by means of a treatment planning system (TPS). SBRT was planned with and without ICT in a lung tumor phantom and ten cases of clinical lung tumors. The results were analyzed from isocenter doses and a dose-volume histogram (DVH): D 95 , D mean , V 20 , V 5 , homogeneity index (HI), and conformity index (CI). The dose attenuation of the ICT modeled with TPS agreed to within ±1% of the actually measured values. The isocenter doses, D 95 and D mean with and without ICT showed differences of 4.1-5% for posterior single field and three fields in the phantom study, and differences of 0.6-2.4% for five fields and rotation in the phantom study and six fields in ten clinical cases. The dose impact of ICT was not significant for five or more fields in SBRT. It is thus possible to reduce the dose effect of ICT by modifying the beam angle and beam weight in the treatment plan. (author)

  11. Combining PET/CT with serum tumor markers to improve the evaluation of histological type of suspicious lung cancers.

    Science.gov (United States)

    Jiang, Rifeng; Dong, Ximin; Zhu, Wenzhen; Duan, Qing; Xue, Yunjing; Shen, Yanxia; Zhang, Guopeng

    2017-01-01

    Histological type is important for determining the management of patients with suspicious lung cancers. In this study, PET/CT combined with serum tumor markers were used to evaluate the histological type of lung lesions. Patients with suspicious lung cancers underwent 18F-FDG PET/CT and serum tumor markers detection. SUVmax of the tumor and serum levels of tumor markers were acquired. Differences in SUVmax and serum levels of tumor markers among different histological types of lung cancers and between EGFR mutation statues of adenocarcinoma were compared. The diagnostic efficiencies of SUVmax alone, each serum tumor marker alone, combined tumor markers and the combination of both methods were further assessed and compared. SCC had the highest level of SUVmax, followed by SCLC and adenocarcinoma, and benign lesions had a lowest level. CYFRA21-1 and SCC-Ag were significantly higher in SCC, NSE was significantly higher in SCLC (Ptumor marker or SUVmax alone. When combined, the AUC, sensitivity and specificity increased significantly (Ptumor markers (P>0.05 for all). SUVmax and serum tumor markers show values in evaluating the histological types of suspicious lung cancers. When properly combined, the diagnostic efficiency can increase significantly.

  12. Interfraction variation in lung tumor position with abdominal compression during stereotactic body radiotherapy

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    Mampuya, Wambaka Ange; Nakamura, Mitsuhiro; Matsuo, Yukinori; Ueki, Nami; Iizuka, Yusuke; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Fujimoto, Takahiro; Yano, Shinsuke [Division of Clinical Radiology Service, Kyoto University Hospital, Kyoto 606-8507 (Japan)

    2013-09-15

    Purpose: To assess the effect of abdominal compression on the interfraction variation in tumor position in lung stereotactic body radiotherapy (SBRT) using cone-beam computed tomography (CBCT) in a larger series of patients with large tumor motion amplitude.Methods: Thirty patients with lung tumor motion exceeding 8 mm who underwent SBRT were included in this study. After translational and rotational initial setup error was corrected based on bone anatomy, CBCT images were acquired for each fraction. The residual interfraction variation was defined as the difference between the centroid position of the visualized target in three dimensions derived from CBCT scans and those derived from averaged intensity projection images. The authors compared the magnitude of the interfraction variation in tumor position between patients treated with [n= 16 (76 fractions)] and without [n= 14 (76 fractions)] abdominal compression.Results: The mean ± standard deviation (SD) of the motion amplitude in the longitudinal direction before abdominal compression was 19.9 ± 7.3 (range, 10–40) mm and was significantly (p < 0.01) reduced to 12.4 ± 5.8 (range, 5–30) mm with compression. The greatest variance of the interfraction variation with abdominal compression was observed in the longitudinal direction, with a mean ± SD of 0.79 ± 3.05 mm, compared to −0.60 ± 2.10 mm without abdominal compression. The absolute values of the 95th percentile of the interfraction variation for one side in each direction were 3.97/6.21 mm (posterior/anterior), 4.16/3.76 mm (caudal/cranial), and 2.90/2.32 mm (right/left) without abdominal compression, and 2.14/5.03 mm (posterior/anterior), 3.93/9.23 mm (caudal/cranial), and 2.37/5.45 mm (right/left) with abdominal compression. An absolute interfraction variation greater than 5 mm was observed in six (9.2%) fractions without and 13 (17.1%) fractions with abdominal compression.Conclusions: Abdominal compression was effective for reducing the amplitude

  13. Diagnostic value of combined detection of serum tumor markers for lung cancer

    International Nuclear Information System (INIS)

    Li Yanping; Wang Qun; Zhao Zihong; Zhou Shan

    2013-01-01

    Objective: To investigate the diagnostic value of combined detection of serum tumor markers, including CEA, CA125, neuron-specific enolase (NSE) and cytokeratin fragment antigen 21-1 (CYFRA21-1) for lung cancer patients. Methods: The subjects involved 138 diagnosed lung cancer patients (82 males, 56 females, average age 58.6 years, from October 2010 to March 2012), 96 patients with benign lung diseases (56 males, 40 females, average age 51.3 years) and 45 healthy adults (30 males, 15 females, average age 43.9 years). The pathological types of lung cancer consisted of 66 squamous cell carcinoma (SCC), 52 adenocarcinoma and 20 small cell lung cancer (SCLC). The serum levels of CEA, CA125, NSE and CYFRA21-1 were measured with electrochemiluminescence immunoassay. The diagnostic efficacy for different pathological types was compared among each single tumor marker and combination of tumor markers. One-way analysis of variance q test were used for statistical analysis. Results: The serum levels of CEA, CA125, NSE and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in healthy subjects (CEA: (19.99±30.99), (10.78±19.77), (3.25±3.42) μg/L; CA125: (79.70±95.98), (44.96±44.97), (20.66±7.13) μg/L; NSE: (35.23±40.22), (15.31±8.42), (13.30±5.65) μg/L; CYFRA21-1: (18.07±43.71), (8.30±8.83), (3.13±1.60) μg/L; F=4.481, 5.436, 4.776, 6.002, all P<0.05). The highest level of CEA, NSE or CYFRA21-1 were found in adenocarcinoma (F=4.932, P<0.05), SCLC (F=5.119, P<0.05) or SCC (F=5.378, P<0.05), respectively. The highest sensitivity tumor markers for SCC, SCLC and adenocarcinoma were CYFRA21-1 (78.8%, 52/66), NSE (75.0%, 15/20) and CEA (57.7%, 30/52), respectively. In combined detection, the highest sensitivity combinations for SCC, SCLC and adenocarcinoma were CEA + CYFRA21-1 + NSE (89.4%, 59/66), CEA + CYFRA21-1 + NSE (80.0%, 16/20) and CEA + CA125 + NSE (78.8%, 41/52), respectively. Conclusions: Combined detection

  14. Prevention of spontaneous and radiation-induced tumors in rats by reduction of food intake

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.

    1990-01-01

    In our previous studies carried out on inbred Sprague-Dawley rats, we reported a striking increase in the incidence of tumors following total-body gamma-irradiation [150 rads (1.5 Gy) five times at weekly intervals]. Subsequently, we observed that two or three irradiations, and to a lesser extent even a single irradiation, were sufficient to induce an impressive increase in the incidence of tumors, particularly in females. A significant reduction of the incidence of radiation-induced tumors resulted when the rats were placed on calorically restricted diet. In experiments reported here, we increased slightly the amount of food given to animals on restricted diet. In the new study, among 102 irradiated females on full diet, 91 (89%) developed tumors, as compared with 29 out of 128 female rats (23%) also irradiated but maintained on restricted diet and 43 out of 89 (48%) untreated control females. None of 77 nonirradiated females on restricted diet developed tumors. Among 65 irradiated male rats, 29 (45%) developed tumors, as compared with 5 out of 74 (7%) rats also irradiated but maintained on restricted diet. Of the 49 males in the nonirradiated groups, 2 (4%) developed tumors. There was a significant weight reduction in both females and males maintained on restricted diet; animals on restricted diet lived longer than those on full diet

  15. Nodal involvement pattern in resectable lung cancer according to tumor location

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    Saeteng S

    2012-06-01

    Full Text Available Somcharoen Saeteng,1 Apichat Tantraworasin,1 Juntima Euathrongchit,2 Nirush Lertprasertsuke,3 Yutthaphun Wannasopha21Department of Surgery, Faculty of Medicine, Chiang Mai University, Thailand, 2Department of Radiology, Faculty of Medicine, Chiang Mai University, Thailand, 3Department of Pathology, Faculty of Medicine, Chiang Mai University, ThailandAbstract: The aim in this study was to define the pattern of lymph node metastasis according to the primary tumor location. In this retrospective cohort study, each of the operable patients diagnosed with lung cancer was grouped by tumor mass location. The International Association for the Study of Lung Cancer nodal chart with stations and zones, established in 2009, was used to define lymph node levels. From 2006 to 2010, 197 patients underwent a lobectomy with systematic nodal resection for primary lung cancer at Chiang Mai University Hospital. There were 123 male and 74 female patients, with ages ranging from 16–85 years old and an average age of 61.31. Analyses of tumor location, histology type, and nodal metastasis were performed. The locations were the right upper lobe in 63 patients (31.98%, the right middle lobe in 18 patients (9.14%, the right lower lobe in 30 patients (15.23%, the left upper lobe in 55 patients (27.92%, the left lower lobe in 16 patients (8.12%, and mixed lobes (more than one lobe in 15 patients (7.61%. The mean tumor size was 4.45 cm in diameter (range 1.2–16.5 cm. Adenocarcinoma was the most common histological type, which occurred in 132 cases (67.01%, followed by squamous cell carcinoma in 41 cases (20.81%, bronchiolo alveolar cell carcinoma in nine cases (4.57%, and large cell carcinoma in seven cases (3.55%. Eighteen cases (9.6% had skip metastasis (mediastinal lymph node metastasis without hilar node metastasis. Adenocarcinoma and intratumoral lymphatic invasion were the predictors of mediastinal lymph node metastases. There were statistically significant

  16. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    Energy Technology Data Exchange (ETDEWEB)

    Knybel, Lukas [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); VŠB-Technical University of Ostrava, Ostrava (Czech Republic); Cvek, Jakub, E-mail: Jakub.cvek@fno.cz [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); Molenda, Lukas; Stieberova, Natalie; Feltl, David [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic)

    2016-11-15

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe

  17. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    International Nuclear Information System (INIS)

    Knybel, Lukas; Cvek, Jakub; Molenda, Lukas; Stieberova, Natalie; Feltl, David

    2016-01-01

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe

  18. Correlation of pretreatment polarographically measured oxygen pressures with quantified contrast-enhanced power doppler ultrasonography in spontaneous canine tumors and their impact on outcome after radiation therapy

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    Rohrer Bley, Carla; Laluhova, Dagmar [Section of Radiooncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Roos, Malgorzata [Inst. for Social and Preventive Medicine, Medical Faculty, Univ. of Zurich (Switzerland); Kaser-Hotz, Barbara [Section of Radiooncology, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Section Imaging Diagnostics, Vetsuisse Faculty, Univ. of Zurich (Switzerland); Ohlerth, Stefanie [Section Imaging Diagnostics, Vetsuisse Faculty, Univ. of Zurich (Switzerland)

    2009-11-15

    Purpose: to evaluate the use of noninvasive quantified contrast-enhanced power Doppler ultrasonography as a surrogate in the estimation of tumor hypoxia measured by invasive pO{sub 2} histography in canine tumors. Material and methods: data of pretreatment tumor oxygenation status, tumor vascularity and blood volume, and tumor response after radiation therapy was collected in 48 spontaneous malignant oral tumors (Table 1). Tumor oxygenation status was correlated to vascularity and blood volume, and influences on outcome after treatment were analyzed. Results: although vascularity and blood volume correlated moderately with median pO{sub 2} (r = 0.51 and 0.61; p = 0.001 and < 0.0001) and percentage of pO{sub 2} readings {<=} 2.5, 5, and 10 mmHg (r = -0.37 to -0.42; p < 0.01-0.03) for all tumors, they did not correlate within the different histology groups (p = 0.06-0.9). For all tumors, pretreatment oxygenation status, vascularity and blood volume were not found to be of prognostic value. Conclusion: these analyses show that quantified contrast-enhanced power Doppler ultrasonography does not represent a non-invasive indirect method to assess tumor hypoxia measured by invasive pO{sub 2} histography. Both technologies were nonprognostic indicators in spontaneous malignant canine oral tumors. (orig.)

  19. Spontaneous Rupture of Recurrent Gastrointestinal Stromal Tumor Associated with Neurofibromatosis Type 1

    Directory of Open Access Journals (Sweden)

    Shin-Mae Wang

    2005-11-01

    Full Text Available The incidence of gastrointestinal stromal tumor (GIST among neurofibromatosis type 1 (NF-1 patients is approximately 3.9–25%, and this relationship is generally considered to be non-coincidental. We report a patient with NF-1 who underwent laparotomy 3 times due to recurrent intra-abdominal tumor rupture with internal bleeding in the space of 13 years. The pathologic diagnoses were schwannoma, malignant peripheral nerve sheath tumor and GIST. Because of the similar histologic features of these tumors, we considered them to be of the same nature. Immunohistochemical staining can help in the differential diagnosis. We suggest that NF-1 patients with gastrointestinal symptoms receive further survey to rule out GISTs.

  20. NSE, CEA and SCC - a useful combination of tumor markers in lung cancer

    International Nuclear Information System (INIS)

    Fischbach, W.; Jany, B.

    1988-01-01

    The usefulness of neuronspecific enolase (NSE), CEA, and of the tumor associated antigen SSC was investigated in 61 patients with histologically proven lung cancer (small cell lung cancer n=25, adenocarcinoma n=14, squamous cell carcinoma n=18 and large cell carcinoma n=4). The sensitivity of NSE was 93.3% in small cell lung cancer (SCLC), whereas in adeno- and squamous cell carcinoma only 8 or 13%, resp., elevated serum NSE were found. CEA was the most sensitive marker for adenocarcinoma (58.3%). Contrary to NSE, however, CEA does not allow any conclusions concerning differential diagnosis as pathological serum concentrations were also observed in 46.6% both in small cell lung cancer and in squamous cell carcinoma. SCC demonstrated a sensitivity of 53% in squamous cell carcinoma. Elevated serum levels were also found in adenocarcinoma (41.6%), but never in small lung cancer. For all three markers tested, high serum concentrations were predominantly present in patients with advanced disease state. (orig.) [de

  1. Tumoral tissue specific promoter hypermethylation of distinct tumor suppressor genes in a case with non--small cell lung carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Arslan Sulhattin

    2008-01-01

    Full Text Available Objective: Non-small cell lung carcinoma is an aggressive phenomenon and the epigenetical alterations of some tumor supressor genes have been reported for the different tumor types. Case Presentation: It is presented a case report concerning a 43 years old male with NSCLC on the lower segment of the right lung. The patient underwent a diag-nostic excisional thin-needle biopsy and after the histological confirmation. We examined the promoter methylation status of some distinct tumor supressor genes in tumoral and blood tissues of the case after sodium bisulfite conversion and DNA amplification with methylation specific multiplex PCR technique. Both tissues were also searched for G to A transitions in codons 12 and 13 of the K-ras proto-oncogene. Results: Tumor specimen showed fully methyl pattern profiles for the SFRP2, p16, DAPK1 and partially hyper-methylated profile for the p53 and MGMT genes in this case with non-small lung carci-noma. Blood speicemen showed normal hypomethylated profiles for all studied TS genes. The K-ras proto-oncogene was in normal structure both in blood and tumoral spiecemens that examined. Conclusion: Results indicate that genes exhibit tumor suppressor activi-ties in blood, but exhibit epigenetic inactivation in carcinoma cell. These findings strongly support the hypothesis that epigenetic mechanisms may play an important role in the non-small cell lung carcinogenesis in human.

  2. Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Il; Ryu, Young Hoon; Lee, Kwang Hun; Choe, Kyu Ok; Kim, Sang Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    2000-01-01

    To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: (1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), (2) the presence of pleural effusion, (3) chest wall or rib invasion, (4) the involvement of a major fissure, (5) extra-pleural fat proliferation, (6) calcified plaque, (7) metastatic lymph nodes, (8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic

  3. Distinguishing the histological and radiological features of cystic lung disease in Birt-Hogg-Dubé syndrome from those of tobacco-related spontaneous pneumothorax.

    Science.gov (United States)

    Fabre, Aurelie; Borie, Raphael; Debray, Marie Pierre; Crestani, Bruno; Danel, Claire

    2014-04-01

    Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited genodermatosis that predisposes to cystic lung disease, leading to spontaneous pneumothoraces. This retrospective analysis of five BHD cases (two men, three women) compared lung histology and computed tomography (CT) imaging to a matched cohort of non-BHD patients with spontaneous pneumothoraces (SPN). Lung was sampled during pleurodesis to resect bullae. Recurrent pneumothoraces was seen in two patients. Fourteen sets of histological slides (seven in each group) and 10 CT scans (five in each group) were reviewed. CT scans in BHD showed multiple cysts with a basal predominance and intraparenchymal/peribronchial distribution. On histological examination, BHD lungs showed punch-out cysts with no inflammation, and lacked subpleural fibroelastotic scars and smoking changes. In contrast, all SPN cases showed respiratory bronchiolitis and subpleural fibroelastotic scars. This study emphasizes the importance of smoking history and topography of the lesions in assessing cystic lung disease. Pathologists need to remain alert to the possibility of BHD in the setting of recurrent pneumothoraces in a non-smoker, in particular in a woman, at any age, and should take part in a multidisciplinary approach to the diagnosis of cystic lung disease to obtain clinical and CT scan details. © 2013 John Wiley & Sons Ltd.

  4. Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

    International Nuclear Information System (INIS)

    Schaake, Eva E.; Rossi, Maddalena M.G.; Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Smit, Adrianus A.J.; Belderbos, José S.A.; Sonke, Jan-Jakob

    2014-01-01

    Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a

  5. Phantom Tumor of the Lung: Localized Interlobar Effusion in Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Mislav Lozo

    2014-01-01

    Full Text Available Localized interlobar effusions in congestive heart failure (phantom or vanishing lung tumor/s is/are uncommon but well known entities. An 83-year-old man presented with shortness of breath, swollen legs, and dry cough enduring five days. Chest-X-ray (CXR revealed massive sharply demarked round/oval homogeneous dense shadow 10 × 7 cm in size in the right inferior lobe. The treatment with the loop diuretics and fluid intake reduction resulted in complete resolution of the observed round/oval tumor-like image on the control CXR three days later. Radiologic appearance of such a mass-like configuration in patients with congestive heart failure demands correction of the underlying heart condition before further diagnostic investigation is performed to avoid unnecessary, expensive, and possibly harmful diagnostic and treatment errors.

  6. The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Pei-Fang Hung

    Full Text Available The motor protein kinesin superfamily proteins (KIFs are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively, and the protein levels were also inversely correlated with metastasis (P<0.0001. The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11 and melanoma cell adhesion molecule (MCAM as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

  7. Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor

    International Nuclear Information System (INIS)

    Ochiai, Satoru; Yamashita, Yasufumi; Nomoto, Yoshihito

    2015-01-01

    The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6–18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1–11.0) and 8.2% (95% CI, 2.9–17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP (P = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2–4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown (P = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors. (author)

  8. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    Energy Technology Data Exchange (ETDEWEB)

    Diamant, A; Ybarra, N; Seuntjens, J [McGill University, Montreal, Quebec (Canada); El Naqa, I [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  9. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    Science.gov (United States)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  10. Dynamic respiratory gated 18FDG-PET of lung tumors - a feasibility study

    International Nuclear Information System (INIS)

    Skjei Knudtsen, Ingerid; Skretting, Arne; Roedal, Jan; Brustugun, Odd Terje; Helland, Aaslaug; Malinen, Eirik

    2011-01-01

    Background. 18 FDG-PET/CT imaging is well established for diagnosis and staging of lung tumors. However, more detailed information regarding the distribution of FDG within the tumor, also as a function of time after injection may be relevant. In this study we explore the feasibility of a combined dynamic and respiratory gated (DR) PET protocol. Material and methods. A DR FDG-PET protocol for a Siemens Biograph 16 PET/CT scanner was set up, allowing data acquisition from the time of FDG injection. Breath-hold (BH) respiratory gating was performed at four intervals over a total acquisition time of 50 minutes. Thus, the PET protocol provides both motion-free images and a spatiotemporal characterization of the glucose distribution in lung tumors. Software tools were developed in-house for tentative tumor segmentation and for extracting standard uptake values (SUVs) voxel by voxel, tumor volumes and SUV gradients in all directions. Results. Four pilot patients have been investigated with the DR PET protocol. The procedure was well tolerated by the patients. The BH images appeared sharper, and SUV max /SUV mean was higher, compared to free breathing (FB) images. Also, SUV gradients in the periphery of the tumor in the BH images were in general greater than or equal to the gradients in the FB PET images. Conclusion. The DR FDG-PET protocol is feasible and the BH images have a superior quality compared to the FB images. The protocol may also provide information of relevance for radiotherapy planning and follow-up. A patient trial is needed for assessing the clinical value of the imaging protocol

  11. Trehalose Liposomes Suppress the Growth of Tumors on Human Lung Carcinoma-bearing Mice by Induction of Apoptosis In Vivo.

    Science.gov (United States)

    Ichihara, Hideaki; Kuwabara, Keiji; Matsumoto, Yoko

    2017-11-01

    Previous evidence demonstrates that trehalose liposomes (DMTreC14) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and α-D-glycopyranosyl-α-D-glucopyranoside monomyristate (TreC14) inhibit proliferation and invasion on lung carcinoma (A549 cells) in vitro. Here, we aimed to investigate suppressive effects of DMTreC14 on the growth of tumor on human lung carcinoma bearing mice. DMTreC14 composed of 30 mol% DMPC and 70 mol% TreC14 were prepared by the sonication method. Anti-tumor activities of DMTreC14 using the subcutaneous and orthotopic graft-bearing mice of A549 cells were investigated in vivo. The remarkable reduction of volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were obtained. Apoptotic-positive cells in the subcutaneous tumor slice of subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were observed using TUNEL staining. Lung weights on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 were markedly decreased compared to those of the control group. Remarkable decrease in dimensions of tumor area of lung on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 was obtained in histological analysis using the hematoxylin and eosin staining. Remarkably high anti-tumor activities of DMTreC14 for the subcutaneous and orthotopic graft-bearing mice of lung carcinoma accompanied with apoptosis were revealed for the first time in vivo. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. A study of tumor motion management in the conformal radiotherapy of lung cancer

    International Nuclear Information System (INIS)

    Burnett, Stuart S.C.; Sixel, Katharina E.; Cheung, Patrick C.F.; Hoisak, Jeremy D.P.

    2008-01-01

    Purpose: To assess the benefit derived from the reduction of planning target volumes (PTVs) afforded by tumor motion management in treatment planning for lung cancer. Methods: We use a simple formula that combines measurements of tumor motion and set-up error for 7 patients to determine PTVs based on the following scenarios: standard uniform 15 mm margin, individualized PTVs (no gating), spirometry-based gating, and active breath-control (ABC). We compare the percent volumes of lung receiving at least 20 Gy (V20) for a standard prescription, and the maximum tolerated doses (MTDs) at fixed V20. In anticipation of improvements in set-up accuracy, we repeat the analysis assuming a reduced set-up margin of 3 mm. Results: Relative to the standard, the average percent reductions in V20 (±1 standard deviation) for the ungated and gated scenarios are 17 ± 5 and 21 ± 8; the percent gains in MTD are 25 ± 12 and 33 ± 11, respectively. For the 3 mm set-up margin, the corresponding results for V20 are 28 ± 7 and 36 ± 7, and for MTD are 57 ± 23 and 79 ± 31. Conclusions: Any form of motion management provides a benefit over the use of a standard margin. The benefit derived from gating compared to the use of ungated individualized PTVs increases with tumor mobility but is generally modest. While motion management may benefit patients with highly mobile tumors, we expect efforts to reduce set-up error to be of greater overall significance. The practical limit for lung PTV margins is likely around 4-5 mm, provided set-up error can be reduced sufficiently

  13. Risk analysis of fatal and incidental lung tumors in wister rats after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    Kai, M.; Akahane, K.; Ogiso, Y.

    2000-01-01

    Cancer risk analysis was done in animal studies for inhalation of plutonium dioxide. Female Wister rats were exposed to an aerosol of plutonium with AMAD of 0.4-0.5 μm and followed up until they died. We made some model analyses using their likelihood function. This approach enables us to consider temporal variation in dose-response analysis. Each rat contributes to the total likelihood depending on fatal or incidental tumors. In Weibul model analysis, the logarithm of the hazard function can be linearly modeled with the term of log (dose), log-L model, and additional term of the square of log (dose), log-LQ model. The likelihood ratio statistics gave a significantly better fit of the log-LQ model. However, if data more than 4 Gy were excluded, there was no significant difference between both models. The ratio of hazard function at 1 Gy and 0 Gy, the excess relative risk, showed 30 for total tumors. This result was much different from those in PNL data (Sanders et al.). The difference of pulmonary deposition depending upon particle size would cause different tumor incidence. Our studies indicated significant increase of occurrence of fatal lung cancer at an average dose of 0.5 Gy and thus did not suggest that a life-span effective threshold for death was about 1 Gy to the lung, which is shown in some papers. In contrast PNL, the incidence of adenoma showing the maximum at 0.5 Gy decreased with increasing lung dose from 1.5 Gy or higher, where malignant tumors such as adenocarcinomas increased. This phenomenon was analyzed with carcinogenesis models. (author)

  14. Multimodality functional imaging of spontaneous canine tumors using 64CU-ATSM and 18FDG PET/CT and dynamic contrast enhanced perfusion CT

    DEFF Research Database (Denmark)

    Hansen, Anders E; Kristensen, Annemarie T; Law, Ian

    2012-01-01

    To compare the distribution and uptake of the hypoxia tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) PET/CT, FDG PET/CT and dynamic contrast enhanced perfusion CT (DCE-pCT) in spontaneous canine tumors. In addition (64)Cu-ATSM distribution over time was evaluated.......To compare the distribution and uptake of the hypoxia tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) PET/CT, FDG PET/CT and dynamic contrast enhanced perfusion CT (DCE-pCT) in spontaneous canine tumors. In addition (64)Cu-ATSM distribution over time was evaluated....

  15. Diagnostic Ability of Percutaneous Needle Biopsy Immediately After Radiofrequency Ablation for Malignant Lung Tumors: An Initial Experience

    International Nuclear Information System (INIS)

    Hasegawa, Takaaki; Kondo, Chiaki; Sato, Yozo; Inaba, Yoshitaka; Yamaura, Hidekazu; Kato, Mina; Murata, Shinichi; Onoda, Yui; Kuroda, Hiroaki; Sakao, Yukinori; Yatabe, Yasushi

    2016-01-01

    PurposeTo evaluate the safety and diagnostic ability of percutaneous needle biopsy performed immediately after lung radiofrequency ablation (RFA).Materials and MethodsFrom May 2013 to April 2014, percutaneous needle biopsy was performed immediately after RFA for 3 patients (2 men and 1 woman, aged 57–76 years) who had lung tumors measuring 1.3–2.6 cm in diameter. All patients had prior history of malignancy, and all tumors were radiologically diagnosed as malignant. Obtained specimens were pathologically classified using standard hematoxylin and eosin staining.ResultsWe completed three planned sessions of RFA followed by percutaneous needle biopsy, all of which obtained tumor tissue that could be pathologically diagnosed. Two tumors were metastatic from renal clear cell carcinoma and rectal adenocarcinoma, respectively; one tumor was primary lung adenocarcinoma. There was no death or major complication related to the procedures. Although pneumothorax occurred in two patients, these resolved without the need for aspiration or chest tube placement. Tumor seeding was not observed, but 21 months after the procedure, one case developed local tumor progression that was treated by additional RFA.ConclusionPathologic diagnosis was possible by needle biopsy immediately after RFA for lung tumors. This technique may reduce the risks and efforts of performing biopsy and RFA on separate occasions.

  16. Diagnostic Ability of Percutaneous Needle Biopsy Immediately After Radiofrequency Ablation for Malignant Lung Tumors: An Initial Experience

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Takaaki, E-mail: t-hasegawa@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kondo, Chiaki [Aichi Cancer Center Hospital, Department of Pathology and Molecular Diagnosis (Japan); Sato, Yozo; Inaba, Yoshitaka; Yamaura, Hidekazu; Kato, Mina; Murata, Shinichi; Onoda, Yui [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kuroda, Hiroaki; Sakao, Yukinori [Aichi Cancer Center Hospital, Department of Thoracic Surgery (Japan); Yatabe, Yasushi [Aichi Cancer Center Hospital, Department of Pathology and Molecular Diagnosis (Japan)

    2016-08-15

    PurposeTo evaluate the safety and diagnostic ability of percutaneous needle biopsy performed immediately after lung radiofrequency ablation (RFA).Materials and MethodsFrom May 2013 to April 2014, percutaneous needle biopsy was performed immediately after RFA for 3 patients (2 men and 1 woman, aged 57–76 years) who had lung tumors measuring 1.3–2.6 cm in diameter. All patients had prior history of malignancy, and all tumors were radiologically diagnosed as malignant. Obtained specimens were pathologically classified using standard hematoxylin and eosin staining.ResultsWe completed three planned sessions of RFA followed by percutaneous needle biopsy, all of which obtained tumor tissue that could be pathologically diagnosed. Two tumors were metastatic from renal clear cell carcinoma and rectal adenocarcinoma, respectively; one tumor was primary lung adenocarcinoma. There was no death or major complication related to the procedures. Although pneumothorax occurred in two patients, these resolved without the need for aspiration or chest tube placement. Tumor seeding was not observed, but 21 months after the procedure, one case developed local tumor progression that was treated by additional RFA.ConclusionPathologic diagnosis was possible by needle biopsy immediately after RFA for lung tumors. This technique may reduce the risks and efforts of performing biopsy and RFA on separate occasions.

  17. Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography

    International Nuclear Information System (INIS)

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J.

    2007-01-01

    Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center

  18. Anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells (SK-MES-1).

    Science.gov (United States)

    Li, W; Wu, D; Wei, B; Wang, S; Sun, Hx; Li, Xl; Zhang, F; Zhang, Cl; Xin, Y

    2014-01-01

    Cactus polysaccharides are the active components of Opuntia dillenii which have been used extensively in folk medicine. In this study, we investigate the anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells SK-MES-1. The inhibitory effect of Cactus polysaccharides on lung squamous carcinoma cells were detected by MTT assay. Cell cycle was determined by flow cytometry and cell apoptosis was determined by AnnexinV assay. Western-blotting was applied to detect P53 and PTEN protein expression in the cells treated with cactus polysaccharides. Results showed that different concentrations of wild cactus polysaccharides prevent SK-MES-1 cells growth and induces S phase arrest. The data also revealed that cactus polysaccharides cause apoptosis in SK-MES-1 cells determined by Annexin-V assay. Furthermore, cactus polysaccharides induced growth arrest and apoptosis may be due to the increase of P53 and phosphatase and tension homolog deleted on chromosome ten (PTEN) protein. Cactus polysaccharides have anti-tumor activity on lung squamous carcinoma cells.

  19. Gene alterations in radiation-induced F344 rat lung tumors

    International Nuclear Information System (INIS)

    Kelly, G.; Hahn, F.F.

    1994-01-01

    The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

  20. Integrin α3β1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma.

    Science.gov (United States)

    Zhou, Bo; Gibson-Corley, Katherine N; Herndon, Mary E; Sun, Yihan; Gustafson-Wagner, Elisabeth; Teoh-Fitzgerald, Melissa; Domann, Frederick E; Henry, Michael D; Stipp, Christopher S

    2014-01-01

    Significant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by approximately 70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced (α3si) cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1's contribution to metastasis in this model. Reexpressing α3 in the α3si cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3si, and α3-rescued cells, all secreted abundant laminin α5 (LAMA5), an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and LAMA5 are both overexpressed. α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin α5 or other α3 integrin ligands are also over-expressed. ©2013 AACR.

  1. Analysis of relationship between tumor markers and quantification of free DNA in serum of lung cancer patients

    International Nuclear Information System (INIS)

    Yang Shunfang; Zhang Peiling; Cao Jie; Zeng Jun; Dong Qianggang

    2006-01-01

    To evaluate the diagnostic value and relationship between five tumor markers (CA19- 9,CA125,CYFRA21-1 ,CEA,NSE) and free DNA in serum for lung cancer detection and try to find a new and more efficient tumor marker, the amounts of CA19-9, CA125, CYFRA21-1, CEA, NSE were determined by RIA and free DNA was determined by the use of quantitative real time PCR amplification of the human epidermal growth factor receptor (EGFR) in 52 lung cancer patients and 8 cases of benign pulmonary disease and 10 healthy controls. The resulls showed that average concentration of free DNA in serum of lung cancer patients, benign pulmo- nary disease and healthy controls was 107.6ng/mL, 76.86ng/mL and 18.8ng/mL, respective- ly. The diagnostic sensitivity, specificity and accuracy of free DNA for lung cancer were 71. 2%, 50% and 68.3%, same as the diagnostic value of combined detection of five tumor markers. The sensitivity, specificity and accuracy of the five tumor markers and free DNA combinend detection for lung cancer were 94.2%, 25% and 85%, respectively. The free DNA in the serum of lung cancer patients may be a new and better tumor marker. (authors)

  2. Lung cancer stem cell: fancy conceptual model of tumor biology or cornerstone of a forthcoming therapeutic breakthrough?

    Science.gov (United States)

    Sourisseau, Tony; Hassan, Khaled A; Wistuba, Ignacio; Penault-Llorca, Frédérique; Adam, Julien; Deutsch, Eric; Soria, Jean-Charles

    2014-01-01

    Cancer research has received a fresh impetus from the concept of cancer stem cell (CSC) which postulates the existence of a tumor cell population uniquely endowed with self-renewal capacity and therapy resistance. Despite recent progresses including targeted therapy, lung cancer treatment remains a challenge owing largely to disease recurrence. Providing a conceptual model of tumor resistance and disease relapse, the lung CSC has received extensive attention, leading to a flourishing literature and several ongoing clinical trials. In this study, we will discuss the data suggesting the existence of CSC in lung tumors and the potential clinical utility of CSCs as prognostic markers or cellular targets of new therapeutic strategies. We will also touch on the new fundamental developments of the CSC concept that ought to be considered if the integration of the CSC concept into clinical practice is to be successful and impact on lung cancer treatment.

  3. Fetal lung interstitial tumor: the first Japanese case report and a comparison with fetal lung tissue and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3.

    Science.gov (United States)

    Yoshida, Mariko; Tanaka, Mio; Gomi, Kiyoshi; Iwanaka, Tadashi; Dehner, Louis P; Tanaka, Yukichi

    2013-10-01

    Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was first reported in 2010. Here, we report the first Japanese case of fetal lung interstitial tumor which was originally diagnosed as atypical congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7-day-old girl was referred to our hospital with respiratory distress and a left lung mass and she subsequently underwent left lower lobectomy. The specimen showed a 5 cm solid mass with a fibrous capsule. Histological examination revealed immature airspaces and interstitium, containing bronchioles and cartilage. The epithelial and interstitial cells contained abundant glycogen granules. Immunohistochemistry showed nuclear/cytoplasmic expression of β-catenin in the epithelial and interstitial cells. β-catenin gene mutations and trisomy 8 were not detected, so a neoplastic origin could not be confirmed. The histological findings were partly consistent with normal fetal lung at the canalicular stage, pulmonary interstitial glycogenosis, and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. In this report, we compare the above conditions and discuss the pathogenesis of fetal lung interstitial tumor. © 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  4. Antitumor and other effects of 24R,25-dihydroxycholecalciferol in Lewis lung carcinoma causing abnormal calcium metabolism in tumor-bearing mice.

    Science.gov (United States)

    Maeda, Y; Yamato, H; Hirai, T; Kobori, N; Fujii, T; Kobayashi, Y; Saitoh, K; Inoguchi, E; Hakozaki, M; Iijima, H

    1988-01-01

    Lewis lung carcinoma was found to cause hypercalcemia in tumor-bearing mice. 24R,25(OH)2D3 (K-DR, prepared by Kureha Chemical Ind.) significantly prolonged the survival time of mice with Lewis lung carcinoma. K-DR exhibited an antimetastatic effect on Lewis lung carcinoma, and also had an analgesic effect in mice with Lewis lung carcinoma.

  5. Grating-based phase-contrast imaging of tumor angiogenesis in lung metastases.

    Directory of Open Access Journals (Sweden)

    Huimin Lin

    Full Text Available To assess the feasibility of the grating-based phase-contrast imaging (GPI technique for studying tumor angiogenesis in nude BALB/c mice, without contrast agents.We established lung metastatic models of human gastric cancer by injecting the moderately differentiated SGC-7901 gastric cancer cell line into the tail vein of nude mice. Samples were embedded in a 10% formalin suspension and dried before imaging. Grating-based X-ray phase-contrast images were obtained at the BL13W beamline of the Shanghai Synchrotron Radiation Facility (SSRF and compared with histological sections.Without contrast agents, grating-based X-ray phase-contrast imaging still differentiated angiogenesis within metastatic tumors with high spatial resolution. Vessels, down to tens of microns, showed gray values that were distinctive from those of the surrounding tumors, which made them easily identifiable. The vessels depicted in the imaging study were similar to those identified on histopathology, both in size and shape.Our preliminary study demonstrates that grating-based X-ray phase-contrast imaging has the potential to depict angiogenesis in lung metastases.

  6. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  7. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Science.gov (United States)

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S; Anthony, Scott M; Sastry, K Jagannadha

    2014-01-01

    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  8. Fluctuations in pO2 in poorly and well-oxygenated spontaneous canine tumors before and during fractionated radiation therapy.

    Science.gov (United States)

    Brurberg, Kjetil G; Skogmo, Hege K; Graff, Bjørn A; Olsen, Dag R; Rofstad, Einar K

    2005-11-01

    The spatial heterogeneity in oxygen tension (pO2) in tumor tissue has been studied extensively, whereas, the information about the temporal heterogeneity is sparse. The purpose of the present study was to search for pO2 fluctuations in untreated and irradiated spontaneous canine tumors, and to investigate whether there is a relationship between overall tumor oxygenation status and pO2 fluctuation pattern. Six dogs scheduled for radiation therapy of head and neck cancer were included in the study. The primary tumors were irradiated with 18 fractions of 3 Gy. Eppendorf polarographic electrodes and OxyLite fluorescence probes were used to measure overall oxygenation status and pO2 fluctuation pattern, respectively. Tissue pO2 was recorded at three subsequent days prior to treatment, and immediately before radiation fraction 4, 7, and 10. Overall oxygenation status differed substantially among the tumors. Radiation therapy had no consistent effect on overall oxygenation status. Fluctuations in pO2 were detected in untreated as well as irradiated tumors, and independent of whether the tumors were poorly or well oxygenated. Fluctuations in pO2 can occur in untreated and irradiated spontaneous canine tumors. There is no correlation between pO2 fluctuation pattern and overall tumor oxygenation status.

  9. Development of diagnostic model of lung cancer based on multiple tumor markers and data mining.

    Science.gov (United States)

    Wang, Zhaoxian; Feng, Feifei; Zhou, Xiaoshan; Duan, Liju; Wang, Jing; Wu, Yongjun; Wang, Na

    2017-11-07

    To develop early intelligent discriminative model of lung cancer and evaluate the efficiency of diagnosis value. Based on the genetic polymorphism profile of CYP1A1-rs1048943, GSTM1, mEH-rs1051740, XRCC1-rs1799782 and XRCC1-rs25489 and the methylations of p16 and RASSF1A gene, and the length of telomere in the peripheral blood from 200 lung cancer patients and 200 health persons, the discriminative model was established through decision tree and ANN technique. ACU of the discriminative model based on multiple tumour markers increased by about 10%; The accuracy rate of decision tree model and ANN model for testing set were 93.00% and 89.62% respectively. The ROC analysis showed the decision tree model's AUC is 0.929 (0.894∼0.964), the ANN model's AUC is 0.894 (0.853∼0.935). However, the classify accuracy rate and AUC of Fisher discriminatory analysis model are all about 0.7. The early intelligent discriminative model of lung cancer based on multiple tumor markers and data mining techniques has a higher accuracy rate and might be useful for early diagnosis of lung cancer.

  10. Measurement of Tumor Volumes Improves RECIST-Based Response Assessments in Advanced Lung Cancer1

    Science.gov (United States)

    Mozley, P David; Bendtsen, Claus; Zhao, Binsheng; Schwartz, Lawrence H; Thorn, Matthias; Rong, Yuanxin; Zhang, Luduan; Perrone, Andrea; Korn, René; Buckler, Andrew J

    2012-01-01

    OBJECTIVE: This study was designed to characterize the reproducibility of measurement for tumor volumes and their longest tumor diameters (LDs) and estimate the potential impact of using changes in tumor volumes instead of LDs as the basis for response assessments. METHODS: We studied patients with advanced lung cancer who have been observed longitudinally with x-ray computed tomography in a multinational trial. A total of 71 time points from 10 patients with 13 morphologically complex target lesions were analyzed. A total of 6461 volume measurements and their corresponding LDs were made by seven independent teams using their own work flows and image analysis tools. Interteam agreement and overall interrater concurrence were characterized. RESULTS: Interteam agreement between volume measurements was better than between LD measurements (ı = 0.945 vs 0.734, P = .005). The variability in determining the nadir was lower for volumes than for LDs (P = .005). Use of standard thresholds for the RECIST-based method and use of experimentally determined cutoffs for categorizing responses showed that volume measurements had a significantly greater sensitivity for detecting partial responses and disease progression. Earlier detection of progression would have led to earlier changes in patient management in most cases. CONCLUSIONS: Our findings indicate that measurement of changes in tumor volumes is adequately reproducible. Using tumor volumes as the basis for response assessments could have a positive impact on both patient management and clinical trials. More authoritative work to qualify or discard changes in volume as the basis for response assessments should proceed. PMID:22348172

  11. Markerless EPID image guided dynamic multi-leaf collimator tracking for lung tumors

    Science.gov (United States)

    Rottmann, J.; Keall, P.; Berbeco, R.

    2013-06-01

    Compensation of target motion during the delivery of radiotherapy has the potential to improve treatment accuracy, dose conformity and sparing of healthy tissue. We implement an online image guided therapy system based on soft tissue localization (STiL) of the target from electronic portal images and treatment aperture adaptation with a dynamic multi-leaf collimator (DMLC). The treatment aperture is moved synchronously and in real time with the tumor during the entire breathing cycle. The system is implemented and tested on a Varian TX clinical linear accelerator featuring an AS-1000 electronic portal imaging device (EPID) acquiring images at a frame rate of 12.86 Hz throughout the treatment. A position update cycle for the treatment aperture consists of four steps: in the first step at time t = t0 a frame is grabbed, in the second step the frame is processed with the STiL algorithm to get the tumor position at t = t0, in a third step the tumor position at t = ti + δt is predicted to overcome system latencies and in the fourth step, the DMLC control software calculates the required leaf motions and applies them at time t = ti + δt. The prediction model is trained before the start of the treatment with data representing the tumor motion. We analyze the system latency with a dynamic chest phantom (4D motion phantom, Washington University). We estimate the average planar position deviation between target and treatment aperture in a clinical setting by driving the phantom with several lung tumor trajectories (recorded from fiducial tracking during radiotherapy delivery to the lung). DMLC tracking for lung stereotactic body radiation therapy without fiducial markers was successfully demonstrated. The inherent system latency is found to be δt = (230 ± 11) ms for a MV portal image acquisition frame rate of 12.86 Hz. The root mean square deviation between tumor and aperture position is smaller than 1 mm. We demonstrate the feasibility of real-time markerless DMLC

  12. Frequency filtering based analysis on the cardiac induced lung tumor motion and its impact on the radiotherapy management

    International Nuclear Information System (INIS)

    Chen, Ting; Qin, Songbing; Xu, Xiaoting; Jabbour, Salma K.; Haffty, Bruce G.; Yue, Ning J.

    2014-01-01

    Purpose/objectives: Lung tumor motion may be impacted by heartbeat in addition to respiration. This study seeks to quantitatively analyze heart-motion-induced tumor motion and to evaluate its impact on lung cancer radiotherapy. Methods/materials: Fluoroscopy images were acquired for 30 lung cancer patients. Tumor, diaphragm, and heart were delineated on selected fluoroscopy frames, and their motion was tracked and converted into temporal signals based on deformable registration propagation. The clinical relevance of heart impact was evaluated using the dose volumetric histogram of the redefined target volumes. Results: Correlation was found between tumor and cardiac motion for 23 patients. The heart-induced motion amplitude ranged from 0.2 to 2.6 mm. The ratio between heart-induced tumor motion and the tumor motion was inversely proportional to the amplitude of overall tumor motion. When the heart motion impact was integrated, there was an average 9% increase in internal target volumes for 17 patients. Dose coverage decrease was observed on redefined planning target volume in simulated SBRT plans. Conclusions: The tumor motion of thoracic cancer patients is influenced by both heart and respiratory motion. The cardiac impact is relatively more significant for tumor with less motion, which may lead to clinically significant uncertainty in radiotherapy for some patients

  13. Spontaneous massive hemorrhage within a malignant tumor of the liver; Diagnostic features in sonography and CT

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Kazunori; Takayasu, Kenichi; Muramatsu, Yukio; Moriyama, Noriyuki; Mizuguchi, Yasunori (National Cancer Center, Tokyo (Japan). Hospital); Sakamoto, Michiie; Hirohashi, Setsuo

    1991-10-01

    Computed tomography (CT) and sonography performed on four patients with histopathologically proven massive intratumoral hemorrhages in the liver were compared with pathological findings. Unenhanced CT showed a round low-density mass, and enhanced CT produced slight enhancements in the peripheral portions of the masses in two patients which corresponded to histopathologically viable cancerous portions. In contrast, sonography showed multiocular cystic masses with variously shaped septa, assuming a honeycomb appearance. Histopathologically, the septa were made up of blood clots with or without granulation tissue, scar and viable tumor, and the cystic spaces were filled with exudate and erythrocytes. Combined study by CT and sonography could be useful in differentiating massive hemorrhagic malignancies from cystic and necrotic masses and/or simple hemorrhagic lesions. The danger of malignant tumors with massive hemorrhage possibly being diagnosed as benign lesions, such as hematomas and abscesses, is also stressed. (author).

  14. Follow-up segmentation of lung tumors in PET and CT data

    Science.gov (United States)

    Opfer, Roland; Kabus, Sven; Schneider, Torben; Carlsen, Ingwer C.; Renisch, Steffen; Sabczynski, Jörg

    2009-02-01

    Early response assessment of cancer therapy is a crucial component towards a more effective and patient individualized cancer therapy. Integrated PET/CT systems provide the opportunity to combine morphologic with functional information. We have developed algorithms which allow the user to track both tumor volume and standardized uptake value (SUV) measurements during the therapy from series of CT and PET images, respectively. To prepare for tumor volume estimation we have developed a new technique for a fast, flexible, and intuitive 3D definition of meshes. This initial surface is then automatically adapted by means of a model-based segmentation algorithm and propagated to each follow-up scan. If necessary, manual corrections can be added by the user. To determine SUV measurements a prioritized region growing algorithm is employed. For an improved workflow all algorithms are embedded in a PET/CT therapy monitoring software suite giving the clinician a unified and immediate access to all data sets. Whenever the user clicks on a tumor in a base-line scan, the courses of segmented tumor volumes and SUV measurements are automatically identified and displayed to the user as a graph plot. According to each course, the therapy progress can be classified as complete or partial response or as progressive or stable disease. We have tested our methods with series of PET/CT data from 9 lung cancer patients acquired at Princess Margaret Hospital in Toronto. Each patient underwent three PET/CT scans during a radiation therapy. Our results indicate that a combination of mean metabolic activity in the tumor with the PET-based tumor volume can lead to an earlier response detection than a purely volume based (CT diameter) or purely functional based (e.g. SUV max or SUV mean) response measures. The new software seems applicable for easy, faster, and reproducible quantification to routinely monitor tumor therapy.

  15. Volume change determination of metastatic lung tumors in CT images using 3-D template matching

    Science.gov (United States)

    Ambrosini, Robert D.; Wang, Peng; O'Dell, Walter G.

    2009-02-01

    The ability of a clinician to properly detect changes in the size of lung nodules over time is a vital element to both the diagnosis of malignant growths and the monitoring of the response of cancerous lesions to therapy. We have developed a novel metastasis sizing algorithm based on 3-D template matching with spherical tumor appearance models that were created to match the expected geometry of the tumors of interest while accounting for potential spatial offsets of nodules in the slice thickness direction. The spherical template that best-fits the overall volume of each lung metastasis was determined through the optimization of the 3-D normalized cross-correlation coefficients (NCCC) calculated between the templates and the nodules. A total of 17 different lung metastases were extracted manually from real patient CT datasets and reconstructed in 3-D using spherical harmonics equations to generate simulated nodules for testing our algorithm. Each metastasis 3-D shape was then subjected to 10%, 25%, 50%, 75% and 90% scaling of its volume to allow for 5 possible volume change combinations relative to the original size per each reconstructed nodule and inserted back into CT datasets with appropriate blurring and noise addition. When plotted against the true volume change, the nodule volume changes calculated by our algorithm for these 85 data points exhibited a high degree of accuracy (slope = 0.9817, R2 = 0.9957). Our results demonstrate that the 3-D template matching method can be an effective, fast, and accurate tool for automated sizing of metastatic tumors.

  16. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  17. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

    Directory of Open Access Journals (Sweden)

    Ayakawa Shiho

    2009-05-01

    Full Text Available Abstract Background In stereotactic body radiotherapy (SBRT for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2 levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC, 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

  18. Combination of intravenous dexmedetomidine with topicalization of airway for placement of double lumen tube in a spontaneously breathing patient of giant lung bullae

    Directory of Open Access Journals (Sweden)

    Vikas Karne

    2016-10-01

    Here we present a patient with giant lung bulla in left lower lobe with severely reduced pulmonary reserves and significant air-trapping posted for VAT assisted bullectomy. Anaesthesia challenges including pathological changes, its effects during induction of anaesthesia, and issues related to placement of double lumen tube in a spontaneously breathing patient are discussed with possible advantages of dexmedetomidine in this special group of patients.

  19. Evaluation of the breath-hold approach in proton therapy of lung tumors

    DEFF Research Database (Denmark)

    Gorgisyan, Jenny

    Proton therapy has the potential to improve the treatment effect as compared to conventional radiation therapy for lung cancer patients. However, the proton therapy delivery is prone to uncertainties caused by anatomical changes and motion during the treatment and between the treatment fractions ....... The change in water-equivalent path length (WEPL) is further shown to be a good predictor of plan robustness, in addition to baseline shifts of the tumor. Overall, the results of this thesis encourage a clinical implementation of the breath-hold approach....

  20. Correlation between tumor size and blood volume in lung tumors. A prospective study on dual-energy gemstone spectral CT imaging

    International Nuclear Information System (INIS)

    Aoki, Masahiko; Takai, Yoshihiro; Narita, Yuichiro

    2014-01-01

    The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and > 3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 μg/cm 3 ), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor. (author)

  1. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.

    Science.gov (United States)

    Travis, William D; Brambilla, Elisabeth; Nicholson, Andrew G; Yatabe, Yasushi; Austin, John H M; Beasley, Mary Beth; Chirieac, Lucian R; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B; Geisinger, Kim; Hirsch, Fred R; Ishikawa, Yuichi; Kerr, Keith M; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A; Tsao, Ming Sound; Wistuba, Ignacio

    2015-09-01

    The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary hamartoma," (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and (c) PEComa, malignant, (12) introducing the entity pulmonary myxoid sarcoma with an EWSR1-CREB1 translocation, (13) adding the entities myoepithelioma and myoepithelial carcinomas, which can show EWSR1 gene rearrangements, (14) recognition of usefulness of WWTR1-CAMTA1 fusions in diagnosis of epithelioid

  2. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    Full Text Available Abstract Background The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Methods Thirty-four companion animals (27 dogs and 7 cats were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. Results The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6% the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17% experienced short lived partial responses (1-3 months duration while all the others died of progressive disease within two months. Conclusions high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of

  3. Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathing control

    Science.gov (United States)

    2010-01-01

    Background To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung. Methods 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. Results The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis. Conclusion The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used. PMID:20187962

  4. Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathing control

    International Nuclear Information System (INIS)

    Shen, Yali; Zhang, Hong; Wang, Jin; Zhong, Renming; Jiang, Xiaoqing; Xu, Qinfeng; Wang, Xin; Bai, Sen; Xu, Feng

    2010-01-01

    To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung. 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis. The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used

  5. Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathing control

    Directory of Open Access Journals (Sweden)

    Wang Xin

    2010-02-01

    Full Text Available Abstract Background To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT guided hypofractionated radiotherapy with active breathing control (ABC for patients with non-small cell lung cancer (NSCLC or metastatic tumors in lung. Methods 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. Results The pre-correction systematic and random errors in the left-right (LR, superior-inferior (SI, anterior-posterior (AP directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20% grade1-2 acute pneumonitis, 3 (15% grade1 acute esophagitis, 2 (10% grade1 late pneumonitis and 1 (5% grade 1 late esophagitis. Conclusion The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.

  6. Impact of Audio-Coaching on the Position of Lung Tumors

    International Nuclear Information System (INIS)

    Haasbeek, Cornelis J.A.; Spoelstra, Femke; Lagerwaard, Frank J.; Soernsen de Koste, John R. van; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh

    2008-01-01

    Purpose: Respiration-induced organ motion is a major source of positional, or geometric, uncertainty in thoracic radiotherapy. Interventions to mitigate the impact of motion include audio-coached respiration-gated radiotherapy (RGRT). To assess the impact of coaching on average tumor position during gating, we analyzed four-dimensional computed tomography (4DCT) scans performed both with and without audio-coaching. Methods and Materials: Our RGRT protocol requires that an audio-coached 4DCT scan is performed when the initial free-breathing 4DCT indicates a potential benefit with gating. We retrospectively analyzed 22 such paired scans in patients with well-circumscribed tumors. Changes in lung volume and position of internal target volumes (ITV) generated in three consecutive respiratory phases at both end-inspiration and end-expiration were analyzed. Results: Audio-coaching increased end-inspiration lung volumes by a mean of 10.2% (range, -13% to +43%) when compared with free breathing (p = 0.001). The mean three-dimensional displacement of the center of ITV was 3.6 mm (SD, 2.5; range, 0.3-9.6mm), mainly caused by displacement in the craniocaudal direction. Displacement of ITV caused by coaching was more than 5 mm in 5 patients, all of whom were in the subgroup of 9 patients showing total tumor motion of 10 mm or more during both coached and uncoached breathing. Comparable ITV displacements were observed at end-expiration phases of the 4DCT. Conclusions: Differences in ITV position exceeding 5 mm between coached and uncoached 4DCT scans were detected in up to 56% of mobile tumors. Both end-inspiration and end-expiration RGRT were susceptible to displacements. This indicates that the method of audio-coaching should remain unchanged throughout the course of treatment

  7. Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity.

    Science.gov (United States)

    Rappa, Germana; Mercapide, Javier; Lorico, Aurelio

    2012-06-01

    Breast cancer progression involves cancer cell heterogeneity, with generation of invasive/metastatic breast cancer cells within populations of nonmetastatic cells of the primary tumor. Sequential genetic mutations, epithelial-to-mesenchymal transition, interaction with local stroma, and formation of hybrids between cancer cells and normal bone marrow-derived cells have been advocated as tumor progression mechanisms. We report herein the spontaneous in vitro formation of heterotypic hybrids between human bone marrow-derived multipotent stromal cells (MSCs) and two different breast carcinoma cell lines, MDA-MB-231 (MDA) and MA11. Hybrids showed predominantly mesenchymal morphological characteristics, mixed gene expression profiles, and increased DNA ploidy. Both MA11 and MDA hybrids were tumorigenic in immunodeficient mice, and some MDA hybrids had an increased metastatic capacity. Both in culture and as xenografts, hybrids underwent DNA ploidy reduction and morphological reversal to breast carcinoma-like morphological characteristics, while maintaining a mixed breast cancer-mesenchymal expression profile. Analysis of coding single-nucleotide polymorphisms by RNA sequencing revealed genetic contributions from both parental partners to hybrid tumors and metastasis. Because MSCs migrate and localize to breast carcinoma, our findings indicate that formation of MSC-breast cancer cell hybrids is a potential mechanism of the generation of invasive/metastatic breast cancer cells. Our findings reconcile the fusion theory of cancer progression with the common observation that breast cancer metastases are generally aneuploid, but not tetraploid, and are histopathologically similar to the primary neoplasm. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response

    Science.gov (United States)

    Levy, Liran; Mishalian, Inbal; Bayuch, Rachel; Zolotarov, Lida; Michaeli, Janna; Fridlender, Zvi G

    2015-01-01

    It has been shown that inhibitors of the immune system reside in the spleen and inhibit the endogenous antitumor effects of the immune system. We hypothesized that splenectomy would inhibit the growth of relatively large non-small lung cancer (NSCLC) tumors by modulating the systemic inhibition of the immune system, and in particular Myeloid Derived Suppressor Cells (MDSC). The effect of splenectomy was evaluated in several murine lung cancer models. We found that splenectomy reduces tumor growth and the development of lung metastases, but only in advanced tumors. In immune-deficient NOD-SCID mice the effect of splenectomy on tumor growth and metastatic spread disappeared. Splenectomy significantly reduced the presence of MDSC, and especially monocytic-MDSC in the circulation and inside the tumor. Specific reduction of the CCR2+ subset of monocytic MDSC was demonstrated, and the importance of the CCL2-CCR2 axis was further shown by a marked reduction in CCL2 following splenectomy. These changes were followed by changes in the macrophages contents of the tumors to become more antitumorigenic, and by increased activation of CD8+ Cytotoxic T-cells (CTL). By MDSC depletion, and adoptive transfer of MDSCs, we demonstrated that the effect of splenectomy on tumor growth was substantially mediated by MDSC cells. We conclude that the spleen is an important contributor to tumor growth and metastases, and that splenectomy can blunt this effect by depletion of MDSC, changing the amount and characteristics of myeloid cells and enhancing activation of CTL. PMID:26137413

  9. Analysis of reproducibility of respiration-triggered gated radiotherapy for lung tumors

    International Nuclear Information System (INIS)

    Spoelstra, Femke O.B.; Soernsen de Koste, John R. van; Cuijpers, Johan P.; Lagerwaard, Frank J.; Slotman, Ben J.; Senan, Suresh

    2008-01-01

    Purpose: Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo-radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a predictable relationship between tumor position and external surrogate, which must be verified during treatment. Time-integrated electronic portal imaging (TI-EPI) identifies mean intra-fractional positions of moving structures, and was used to study reproducibility of anatomy during RGRT for lung tumors. Materials and methods: TI-EPIs were acquired using an amorphous silicon-based electronic portal imaging system (EPID, aS500) in continuous image acquisition mode in 11 patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All TI-EPI portals were co-registered to corresponding digitally reconstructed radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in tumor position or that of an adjacent bronchus during RGRT was measured relative to the reference structure on the DRR. Results: Vertebra-matched portals revealed systematic (Σ) and random (σ) errors of 1.8 and 1.3 mm in medial-lateral direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a reproducible tumor/bronchus position during the RPM-triggered gates. Conclusions: RGRT delivery at end-inspiration can achieve reproducible internal anatomy in 'gated' fields delivered with audio-coaching

  10. Clinical Trials of Immunogene Therapy for Spontaneous Tumors in Companion Animals

    Science.gov (United States)

    Glikin, Gerardo Claudio; Finocchiaro, Liliana María Elena

    2014-01-01

    Despite the important progress obtained in the treatment of some pets' malignancies, new treatments need to be developed. Being critical in cancer control and progression, the immune system's appropriate modulation may provide effective therapeutic options. In this review we summarize the outcomes of published immunogene therapy veterinary clinical trials reported by many research centers. A variety of tumors such as canine melanoma, soft tissue sarcomas, osteosarcoma and lymphoma, feline fibrosarcoma, and equine melanoma were subjected to different treatment approaches. Both viral and mainly nonviral vectors were used to deliver gene products as cytokines, xenogeneic tumor associated antigens, specific ligands, and proapoptotic regulatory factors. In some cases autologous, allogenic, or xenogeneic transgenic cytokine producing cells were assayed. In general terms, minor or no adverse collateral effects appeared during this kind of therapies and treated patients usually displayed a better course of the disease (longer survival, delayed or suppressed recurrence or metastatic spread, and improvement of the quality of life). This suggests the utility of these methodologies as standard adjuvant treatments. The encouraging outcomes obtained in companion animals support their ready application in veterinary clinical oncology and serve as preclinical proof of concept and safety assay for future human gene therapy trials. PMID:25506617

  11. Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Peppoloni, S.; Herberman, R.B.; Gorelik, E.

    1985-01-01

    This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated tum- (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth

  12. The clinical significance of the tumor cell D2-40 immunoreactivity in non-small cell lung cancer.

    Science.gov (United States)

    Kadota, Kyuichi; Huang, Cheng-Long; Liu, Dage; Nakashima, Nariyasu; Yokomise, Hiroyasu; Ueno, Masaki; Haba, Reiji

    2010-10-01

    A monoclonal antibody D2-40 has been widely used for tumor lymphangiogenesis and lymphatic vessel invasion (LVI) in human cancers. However, the clinical significance of the tumor cell D2-40 immunoreactivity has not been clearly understood. We evaluated the tumor cell D2-40 immunoreactivity in non-small cell lung cancer (NSCLC). One hundred and forty-seven NSCLC patients were investigated. Immunohistochemistry using D2-40 was performed to evaluate the tumor cell D2-40 immunoreactivity, micro-lymphatic vessel density (Micro-LVD) and LVI. The intratumoral microvessels density (MVD) was evaluated by the CD34-immunostaining, and tumor proliferation was evaluated by the Ki-67-immunostaining. The percentage of D2-40-positive tumor cells was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001), and all D2-40-strong tumors were squamous cell carcinomas. The percentage of D2-40-strong tumors was significantly higher in moderately to poorly differentiated tumors than in well-differentiated tumors (P=0.0332). Furthermore, the Ki-67 proliferation index in D2-40-strong tumors was significantly the highest. However, the tumor cell D2-40 immunoreactivity was not associated with Micro-LVD, LVI, or MVD. Regarding the patient survival, the overall survival was significantly lower in patients with D2-40-strong tumors than in patients with D2-40-negative or D2-40-weak tumors (P=0.0005). Multivariate analyses also revealed the tumor cell D2-40 immunoreactivity to be a significant prognostic factor of poor prognosis for NSCLC patients (P=0.0007). The D2-40 immunostaining is useful to identify aggressive squamous cell carcinomas of the lung. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  13. SU-E-J-23: An Accurate Algorithm to Match Imperfectly Matched Images for Lung Tumor Detection Without Markers

    International Nuclear Information System (INIS)

    Rozario, T; Bereg, S; Chiu, T; Liu, H; Kearney, V; Jiang, L; Mao, W

    2014-01-01

    Purpose: In order to locate lung tumors on projection images without internal markers, digitally reconstructed radiograph (DRR) is created and compared with projection images. Since lung tumors always move and their locations change on projection images while they are static on DRRs, a special DRR (background DRR) is generated based on modified anatomy from which lung tumors are removed. In addition, global discrepancies exist between DRRs and projections due to their different image originations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported. Methods: This method divides global images into a matrix of small tiles and similarities will be evaluated by calculating normalized cross correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) will be automatically optimized to keep the tumor within a single tile which has bad matching with the corresponding DRR tile. A pixel based linear transformation will be determined by linear interpolations of tile transformation results obtained during tile matching. The DRR will be transformed to the projection image level and subtracted from it. The resulting subtracted image now contains only the tumor. A DRR of the tumor is registered to the subtracted image to locate the tumor. Results: This method has been successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (Brainlab) for dynamic tumor tracking on phantom studies. Radiation opaque markers are implanted and used as ground truth for tumor positions. Although, other organs and bony structures introduce strong signals superimposed on tumors at some angles, this method accurately locates tumors on every projection over 12 gantry angles. The maximum error is less than 2.6 mm while the total average error is 1.0 mm. Conclusion: This algorithm is capable of detecting tumor without markers despite strong background signals

  14. A Gaussian mixture model for definition of lung tumor volumes in positron emission tomography

    International Nuclear Information System (INIS)

    Aristophanous, Michalis; Penney, Bill C.; Martel, Mary K.; Pelizzari, Charles A.

    2007-01-01

    The increased interest in 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in radiation treatment planning in the past five years necessitated the independent and accurate segmentation of gross tumor volume (GTV) from FDG-PET scans. In some studies the radiation oncologist contours the GTV based on a computed tomography scan, while incorporating pertinent data from the PET images. Alternatively, a simple threshold, typically 40% of the maximum intensity, has been employed to differentiate tumor from normal tissue, while other researchers have developed algorithms to aid the PET based GTV definition. None of these methods, however, results in reliable PET tumor segmentation that can be used for more sophisticated treatment plans. For this reason, we developed a Gaussian mixture model (GMM) based segmentation technique on selected PET tumor regions from non-small cell lung cancer patients. The purpose of this study was to investigate the feasibility of using a GMM-based tumor volume definition in a robust, reliable and reproducible way. A GMM relies on the idea that any distribution, in our case a distribution of image intensities, can be expressed as a mixture of Gaussian densities representing different classes. According to our implementation, each class belongs to one of three regions in the image; the background (B), the uncertain (U) and the target (T), and from these regions we can obtain the tumor volume. User interaction in the implementation is required, but is limited to the initialization of the model parameters and the selection of an ''analysis region'' to which the modeling is restricted. The segmentation was developed on three and tested on another four clinical cases to ensure robustness against differences observed in the clinic. It also compared favorably with thresholding at 40% of the maximum intensity and a threshold determination function based on tumor to background image intensities proposed in a recent paper. The parts of the

  15. Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors.

    Science.gov (United States)

    Moris, Dimitrios; Ntanasis-Stathopoulos, Ioannis; Tsilimigras, Diamantis I; Adam, Mohamad A; Yang, Chi-Fu Jeffrey; Harpole, David; Theocharis, Stamatios

    2018-01-01

    Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance. This review provides an insight into promising molecules and genes that are implicated in NET carcinogenesis, cell-cycle regulation, chromatin remodeling, apoptosis, intracellular cascades and cell-cell interactions. Additionally it supports a basis for classifying these tumors into categories that distinct molecular characteristics and disease natural history, which may have a direct impact on treatment options. In light of the recent approval of everolimus, mammalian target of rapamycin pathway inhibition and related biomarkers may play a central role in the treatment of pulmonary NETs. Future clinical trials that integrate molecular profiling are deemed necessary in order to treat patients with NET on a personalized basis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Mohamad Saekhu

    2016-07-01

    Full Text Available Background: The outcome of patients with spontaneous supratentorial intracerebral hemorrhage (SSICH is unsatisfactory. Inflammatory response secondary to brain injury as well as those resulted from surgical procedure were considered responsible of this outcome. This study was intended to elucidate the anti-inflammatory activity of tigecycline by measuring TNF-α level and its neuroprotective effect as represented by inhospital mortality rate.Methods: Patients with SSICH who were prepared for hematoma evacuation were randomized to receive either tigecycline (n=35 or fosfomycine (n=37 as prophylactic antibiotic. TNF-α level was measured in all subjects before surgery and postoperatively on day-1 and day-7. A repeated brain CT Scan was performed on postoperative day-7. The Glasgow outcome scale (GOS and length of stay (LOS were recorded at the time of hospital discharge. Data were analyzed using Mann-Whitney and Chi square test. Relative clinical effectiveness was measured by calculating the number needed to treat (NNT.Results: There was a significant difference regarding the proportion of subject who had  reduced TNF-α level on postoperative day-7 between the groups receiving tigecycline and fosfomycine (62% vs 29%, p=0.022. Decrease brain edema on CT control (86% vs 80%, p=0.580. Tigecycline administration showed a tendency of better clinical effectiveness in lowering inhospital mortality (17% vs 35%; p=0.083; OR=0.49; NNT=5 and worse clinical outcome / GOS ≤ 2 (20% vs 38% ; p=0.096; OR=0.41; NNT=6. LOS ≥ 15 hari ( 40% vs 27%; p=0.243; OR=1.81; NNT=8.Conclusion: Tigecycline showed anti-inflammatory and neuroprotective activities. These activities were associated with improved clinical outcome in patients with SSICH after hematoma evacuation.

  17. Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Jung, Chi Young; Antonia, Scott J

    2018-01-01

    Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

  18. The influence of the pituitary tumor transforming gene-1 (PTTG-1 on survival of patients with small cell lung cancer and non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Geddert Helene

    2006-01-01

    Full Text Available Abstract Background PTTG-1 (pituitary tumor transforming gene is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Methods Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC and 91 patients with non-small cell lung cancer (NSCLC, retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. Results PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 ± 18 days vs. 379 ± 66 days; p = 0.0291. Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 ± 58 days compared with 463 ± 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386. Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Conclusion Lung cancers belong to the group of tumors expressing

  19. The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer.

    Science.gov (United States)

    Rehfeld, Nina; Geddert, Helene; Atamna, Abedelsalam; Rohrbeck, Astrid; Garcia, Guillermo; Kliszewski, Slawek; Neukirchen, Judith; Bruns, Ingmar; Steidl, Ulrich; Fenk, Roland; Gabbert, Helmut E; Kronenwett, Ralf; Haas, Rainer; Rohr, Ulrich-Peter

    2006-01-20

    PTTG-1 (pituitary tumor transforming gene) is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC) and 91 patients with non-small cell lung cancer (NSCLC), retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 +/- 18 days vs. 379 +/- 66 days; p = 0.0291). Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 +/- 58 days compared with 463 +/- 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386). Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Lung cancers belong to the group of tumors expressing PTTG-1. Dependent on the histological subtype of lung

  20. WE-G-BRD-05: Inline Magnetic Fields Enhance Tumor Dose for Small Lung Cancers

    International Nuclear Information System (INIS)

    Oborn, B; Ge, Y; Hardcastle, N; Metcalfe, P; Keall, P

    2015-01-01

    Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: 9 clinical lung plans were recalculated using Monte Carlo methods and external inline (parallel to the beam direction) magnetic fields of 0.5 T, 1.0 T and 3 T were included. Three plans were 6MV 3D-CRT and six were 6MV IMRT. The GTV’s ranged from 0.8 cc to 73 cc, while the PTV ranged from 1 cc to 180 cc. Results: The inline magnetic field has a moderate impact in lung dose distributions by reducing the lateral scatter of secondary electrons and causing a small local dose increase. Superposition of multiple small beams acts to superimpose the small dose increases and can lead to significant dose enhancements, especially when the GTV is low density. Two plans with very small, low mean density GTV’s (<1 cc, ρ(mean)<0.35g/cc) showed uniform increases of 16% and 23% at 1 T throughout the PTV. Three plans with moderate mean density PTV’s (3–13 cc, ρ(mean)=0.58–0.67 g/cc) showed 6% mean dose enhancement at 1 T in the PTV, however not uniform throughout the GTV/PTV. Replanning would benefit these cases. The remaining 5 plans had large dense GTV’s (∼ 1 g/cc) and so only a minimal (<2%) enhancement was seen. In general the mean dose enhancement at 0.5 T was 60% less than 1 T, while 5–50% higher at 3 T. Conclusions: A paradigm shift in the efficacy of small lung tumor radiotherapy is predicted with future inline MRI-linac systems. This will be achieved by carefully taking advantage of the reduction of lateral electronic disequilibrium withing lung tissue that is induced naturally inside strong inline magnetic fields

  1. The potential of positron emission tomography for intratreatment dynamic lung tumor tracking: A phantom study

    International Nuclear Information System (INIS)

    Yang, Jaewon; Yamamoto, Tokihiro; Mazin, Samuel R.; Graves, Edward E.; Keall, Paul J.

    2014-01-01

    Purpose: This study aims to evaluate the potential and feasibility of positron emission tomography for dynamic lung tumor tracking during radiation treatment. The authors propose a center of mass (CoM) tumor tracking algorithm using gated-PET images combined with a respiratory monitor and investigate the geometric accuracy of the proposed algorithm. Methods: The proposed PET dynamic lung tumor tracking algorithm estimated the target position information through the CoM of the segmented target volume on gated PET images reconstructed from accumulated coincidence events. The information was continuously updated throughout a scan based on the assumption that real-time processing was supported (actual processing time at each frame ≈10 s). External respiratory motion and list-mode PET data were acquired from a phantom programmed to move with measured respiratory traces (external respiratory motion and internal target motion) from human subjects, for which the ground truth target position was known as a function of time. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The measured respiratory traces consisted of two sets: (1) 1D-measured motion from ten healthy volunteers and (2) 3D-measured motion from four lung cancer patients. The authors evaluated the geometric accuracy of the proposed algorithm by quantifying estimation errors (Euclidean distance) between the actual motion of targets (1D-motion and 3D-motion traces) and CoM trajectories estimated by the proposed algorithm as a function of time. Results: The time-averaged error of 1D-motion traces over all trajectories of all targets was 1.6 mm. The error trajectories decreased with time as coincidence events were accumulated. The overall error trajectory of 1D-motion traces converged to within 2 mm in approximately 90 s. As expected, more accurate results were obtained for larger targets. For example, for the 37 mm target, the average error over all 1D

  2. Definition of gross tumor volume in lung cancer: inter-observer variability

    International Nuclear Information System (INIS)

    Van de Steene, Jan; Linthout, Nadine; Mey, Johan de; Vinh-Hung, Vincent; Claassens, Cornelia; Noppen, Marc; Bel, Arjan; Storme, Guy

    2002-01-01

    Background and purpose: To determine the inter-observer variation in gross tumor volume (GTV) definition in lung cancer, and its clinical relevance. Material and methods: Five clinicians involved in lung cancer were asked to define GTV on the planning CT scan of eight patients. Resulting GTVs were compared on the base of geometric volume, dimensions and extensions. Judgement of invasion of lymph node (LN) regions was evaluated using the ATS/LCSG classification of LN. Clinical relevance of the variation was studied through 3D-dosimetry of standard conformal plans: volume of critical organs (heart, lungs, esophagus, spinal cord) irradiated at toxic doses, 95% isodose volumes of GTVs, normal tissue complication probabilities (NTCP) and tumor control probabilities (TCP) were compared for evaluation of observer variability. Results: Before evaluation of observer variability, critical review of planning CT scan led to up- (two cases) and downstaging (one case) of patients as compared to the respective diagnostic scans. The defined GTVs showed an inter-observer variation with a ratio up to more than 7 between maximum and minimum geometric content. The dimensions of the primary tumor had inter-observer ranges of 4.2 (transversal), 7.9 (cranio-caudal) and 5.4 (antero-posterior) cm. Extreme extensions of the GTVs (left, right, cranial, caudal, anterior and posterior) varied with ranges of 2.8-7.3 cm due to inter-observer variation. After common review, only 63% of involved lymph node regions were delineated by the clinicians (i.e. 37% are false negative). Twenty-two percent of drawn in lymph node regions were accepted to be false positive after review. In the conformal plans, inter-observer ranges of irradiated normal tissue volume were on average 12%, with a maximum of 66%. The probability (in the population of all conformal plans) of irradiating at least 95% of the GTV with at least 95% of the nominal treatment dose decreased from 96 to 88% when swapping the matched GTV

  3. A block matching-based registration algorithm for localization of locally advanced lung tumors.

    Science.gov (United States)

    Robertson, Scott P; Weiss, Elisabeth; Hugo, Geoffrey D

    2014-04-01

    To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Small (1 cm(3)), nonoverlapping image subvolumes ("blocks") were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4-7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%-100%) in the initial bony alignment to 91% ± 8% (range: 56%-100%;p < 0.001). Left-right, anterior-posterior, and

  4. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  5. A block matching-based registration algorithm for localization of locally advanced lung tumors

    International Nuclear Information System (INIS)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

  6. Esophagus sparing with IMRT in lung tumor irradiation: An EUD-based optimization technique

    International Nuclear Information System (INIS)

    Chapet, Olivier; Thomas, Emma; Kessler, Marc L.; Fraass, Benedick A.; Ten Haken, Randall K.

    2005-01-01

    Purpose: The aim of this study was to evaluate (1) the use of generalized equivalent uniform dose (gEUD) to optimize dose escalation of lung tumors when the esophagus overlaps the planning target volume (PTV) and (2) the potential benefit of further dose escalation in only the part of the PTV that does not overlap the esophagus. Methods and Materials: The treatment-planning computed tomography (CT) scans of patients with primary lung tumors located in different regions of the left and right lung were used for the optimization of beamlet intensity modulated radiation therapy (IMRT) plans. In all cases, the PTV overlapped part of the esophagus. The dose in the PTV was maximized according to 7 different primary cost functions: 2 plans that made use of mean dose (MD) (the reference plan, in which the 95% isodose surface covered the PTV and a second plan that had no constraint on the minimum isodose), 3 plans based on maximizing gEUD for the whole PTV with ever increasing assumptions for tumor aggressiveness, and 2 plans that used different gEUD values in 2 simultaneous, overlapping target volumes (the whole PTV and the PTV minus esophagus). Beam arrangements and NTCP-based costlets for the organs at risk (OARs) were kept identical to the original conformal plan for each case. Regardless of optimization method, the relative ranking of the resulting plans was evaluated in terms of the absence of cold spots within the PTV and the final gEUD computed for the whole PTV. Results: Because the MD-optimized plans lacked a constraint on minimum PTV coverage, they resulted in cold spots that affected approximately 5% of the PTV volume. When optimizing over the whole PTV volume, gEUD-optimized plans resulted in higher equivalent uniform PTV doses than did the reference plan while still maintaining normal-tissue constraints. However, only under the assumption of extremely aggressive tumors could cold spots in the PTV be avoided. Generally, high-level overall results are obtained

  7. Impact of respiratory movement on the computed tomographic images of small lung tumors in three-dimensional (3D) radiotherapy

    International Nuclear Information System (INIS)

    Shimizu, Shinichi; Shirato, Hiroki; Kagei, Kenji; Nishioka, Takeshi; Bo Xo; Dosaka-Akita, Hirotoshi; Hashimoto, Seiko; Aoyama, Hidefumi; Tsuchiya, Kazuhiko; Miyasaka, Kazuo

    2000-01-01

    Purpose: Three-dimensional (3D) treatment planning has often been performed while patients breathe freely, under the assumption that the computed tomography (CT) images represent the average position of the tumor. We investigated the impact of respiratory movement on the free-breathing CT images of small lung tumors using sequential CT scanning at the same table position. Methods: Using a preparatory free-breathing CT scan, the patient's couch was fixed at the position where each tumor showed its maximum diameter on image. For 16 tumors, over 20 sequential CT images were taken every 2 s, with a 1-s acquisition time occurring during free breathing. For each tumor, the distance between the surface of the CT table and the posterior border of the tumor was measured to determine whether the edge of the tumor was sufficiently included in the planning target volume (PTV) during normal breathing. Results: In the sequential CT scanning, the tumor itself was not visible in the examination slice in 21% (75/357) of cases. There were statistically significant differences between lower lobe tumors (39.4%, 71/180) and upper lobe tumors (0%, 0/89) (p < 0.01) and between lower lobe tumors and middle lobe tumor (8.9%, 4/45) (p < 0.01) in the incidence of the disappearance of the tumor from the image. The mean difference between the maximum and minimum distances between the surface of the CT table and the posterior border of the tumor was 6.4 mm (range 2.1-24.4). Conclusion: Three-dimensional treatment planning for lung carcinoma would significantly underdose many lesions, especially those in the lower lobe. The excess 'safety margin' might call into question any additional benefit of 3D treatment. More work is required to determine how to control respiratory movement

  8. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

    2014-08-21

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  9. Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

    Science.gov (United States)

    Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

    2017-07-15

    The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells.

    Science.gov (United States)

    Wang, Jianyu; Sun, Zhiwei; Liu, Yongli; Kong, Liangsheng; Zhou, Shixia; Tang, Junlin; Xing, Hongmei Rosie

    2017-11-14

    Characterization of the stem-like properties of cancer stem cells (CSCs) remain indirect and qualitative, especially the ability of CSCs to undergo asymmetric cell division for self renewal and differentiation, a unique property of cells of stem origin. It is partly due to the lack of stable cellular models of CSCs. In this study, we developed a new approach for CSC isolation and purification to derive a CSC-enriched cell line (LLC-SE). By conducting five consecutive rounds of single cell cloning using the LLC-SE cell line, we obtained two distinct sub-population of cells within the Lewis lung cancer CSCs that employed largely symmetric division for self-renewal (LLC-SD) or underwent asymmetric division for differentiation (LLC-ASD). LLC-SD and LLC-ASD cell lines could be stably passaged in culture and be distinguished by cell morphology, stem cell marker, spheroid formation and subcutaneous tumor initiation efficiency, as well as orthotopic lung tumor growth, progression and survival. The ability LLC-ASD cells to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division. The more stem-like LLC-SD cells exhibited higher capacity for tumorigenesis and progression and shorter survival. As few as 10 LLC-SD could initiate subcutaneous tumor growth when transplanted to the athymic mice. Collectively, these observations suggest that the SD-type of cells appear to be on the top of the hierarchical order of the CSCs. Furthermore, they have lead to generated cellular models of CSC self-renewal for future mechanistic investigations.

  11. Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells

    Science.gov (United States)

    Wang, Jianyu; Sun, Zhiwei; Liu, Yongli; Kong, Liangsheng; Zhou, Shixia; Tang, Junlin; Xing, Hongmei Rosie

    2017-01-01

    Characterization of the stem-like properties of cancer stem cells (CSCs) remain indirect and qualitative, especially the ability of CSCs to undergo asymmetric cell division for self renewal and differentiation, a unique property of cells of stem origin. It is partly due to the lack of stable cellular models of CSCs. In this study, we developed a new approach for CSC isolation and purification to derive a CSC-enriched cell line (LLC-SE). By conducting five consecutive rounds of single cell cloning using the LLC-SE cell line, we obtained two distinct sub-population of cells within the Lewis lung cancer CSCs that employed largely symmetric division for self-renewal (LLC-SD) or underwent asymmetric division for differentiation (LLC-ASD). LLC-SD and LLC-ASD cell lines could be stably passaged in culture and be distinguished by cell morphology, stem cell marker, spheroid formation and subcutaneous tumor initiation efficiency, as well as orthotopic lung tumor growth, progression and survival. The ability LLC-ASD cells to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division. The more stem-like LLC-SD cells exhibited higher capacity for tumorigenesis and progression and shorter survival. As few as 10 LLC-SD could initiate subcutaneous tumor growth when transplanted to the athymic mice. Collectively, these observations suggest that the SD-type of cells appear to be on the top of the hierarchical order of the CSCs. Furthermore, they have lead to generated cellular models of CSC self-renewal for future mechanistic investigations. PMID:29228576

  12. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    Directory of Open Access Journals (Sweden)

    Erickson-Miller Connie L

    2012-09-01

    Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

  13. Imaging of lung metastasis tumor mouse model using [{sup 18}F]FDG small animal PET and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, June Youp; Woo, Sang Keun; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)] (and others)

    2007-02-15

    The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [{sup 18}F]FDG small animal PET and clinical CT. The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 .deg. C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [{sup 18}F]FDG and compared pattern of [{sup 18}F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [{sup 18}F]FDG image was obtained and fused with anatomical clinical CT image. Average blood glucose concentration in normal mice were 128.0 {+-} 22.87 and 86.0 {+-} 21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6 {+-} 0.48 and 12.1 {+-}0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [{sup 18}F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [{sup 18}F]FDG small animal PET image was confirmed by fusion image using clinical CT. Tumor imaging in small animal lung region with [{sup 18}F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [{sup 18}F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

  14. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors.

    Science.gov (United States)

    Erickson-Miller, Connie L; Pillarisetti, Kodandaram; Kirchner, Jennifer; Figueroa, David J; Ottesen, Lone; Martin, Anne-Marie; Liu, Yuan; Kamel, Yasser Mostafa; Messam, Conrad

    2012-09-11

    Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and for TPO-R protein expression by immunohistochemistry (IHC). Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43%) and malignant (3-17%) breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and megakaryocyte precursors.

  15. Intravascular placement of metallic coils as lung tumor markers for CyberKnife stereotactic radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Karaman, Kutlay; Dokdok, A. Murat; Karadeniz, Okatay; Ceylan, Cemile; Engin, Kayihan [Anadolu Medical Center, Kocaeli (Turkey)

    2015-06-15

    To present our experience with placing endovascular coils in pulmonary arteries used as a fiducial marker for CyberKnife therapy and to describe the technical details and complications of the procedure. Between June 2005 and September 2013, 163 patients with primary or secondary lung malignancies, referred for fiducial placement for stereotactic radiosurgery, were retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years) with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement. Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted through coaxial microcatheters into a small distal pulmonary artery in the vicinity of the tumor under biplane angiography/fluoroscopy guidance. Forty nine coils with a median number of 3 coils per tumor were placed with a mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were successfully used as fiducial markers. Two coils could not be used due to a larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No major complications needing further medication other than nominal therapy, hospitalization more than one night or permanent adverse sequale were observed. Endovascular placement of coil as a fiducial marker is safe and feasible during CyberKnife therapy, and might be an option for the patients in which percutaneous transthoracic fiducial placement might be risky.

  16. Intravascular placement of metallic coils as lung tumor markers for CyberKnife stereotactic radiation therapy

    International Nuclear Information System (INIS)

    Karaman, Kutlay; Dokdok, A. Murat; Karadeniz, Okatay; Ceylan, Cemile; Engin, Kayihan

    2015-01-01

    To present our experience with placing endovascular coils in pulmonary arteries used as a fiducial marker for CyberKnife therapy and to describe the technical details and complications of the procedure. Between June 2005 and September 2013, 163 patients with primary or secondary lung malignancies, referred for fiducial placement for stereotactic radiosurgery, were retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years) with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement. Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted through coaxial microcatheters into a small distal pulmonary artery in the vicinity of the tumor under biplane angiography/fluoroscopy guidance. Forty nine coils with a median number of 3 coils per tumor were placed with a mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were successfully used as fiducial markers. Two coils could not be used due to a larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No major complications needing further medication other than nominal therapy, hospitalization more than one night or permanent adverse sequale were observed. Endovascular placement of coil as a fiducial marker is safe and feasible during CyberKnife therapy, and might be an option for the patients in which percutaneous transthoracic fiducial placement might be risky.

  17. Measurement of ventilation- and perfusion-mediated cooling during laser ablation in ex vivo human lung tumors.

    Science.gov (United States)

    Vietze, Andrea; Koch, Franziska; Laskowski, Ulrich; Linder, Albert; Hosten, Norbert

    2011-11-01

    Perfusion-mediated tissue cooling has often been described in the literature for thermal ablation therapies of liver tumors. The objective of this study was to investigate the cooling effects of both perfusion and ventilation during laser ablation of lung malignancies. An ex vivo lung model was used to maintain near physiological conditions for the specimens. Fourteen human lung lobes containing only primary lung tumors (non-small cell lung cancer) were used. Laser ablation was carried out using a Nd:YAG laser with a wavelength of 1064 nm and laser fibers with 30 mm diffusing tips. Continuous invasive temperature measurement in 10 mm distance from the laser fiber was performed. Laser power was increased at 2 W increments starting at 10 W up to a maximum power of 12-20 W until a temperature plateau around 60 °C was reached at one sensor. Ventilation and perfusion were discontinued for 6 min each to assess their effects on temperature development. The experiments lead to 25 usable temperature profiles. A significant temperature increase was observed for both discontinued ventilation and perfusion. In 6 min without perfusion, the temperature rose about 5.5 °C (mean value, Pcooling are significant influencing factors on temperature development during thermal ablation. They should be taken into account during the planning and preparation of minimally invasive lung tumor treatment in order to achieve complete ablation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

    International Nuclear Information System (INIS)

    Hanley, J.; Debois, M.M.; Raben, A.; Mageras, G.S.; Lutz, W.R.; Mychalczak, B.; Schwartz, L.H.; Gloeggler, P.J.; Leibel, S.A.; Fuks, Z.; Kutcher, G.J.

    1996-01-01

    Purpose/Objective: Lung tumors are subject to movement due to respiratory motion. Conventionally, a margin is applied to the clinical target volume (CTV) to account for this and other treatment uncertainties. The purpose of this study is to evaluate the dosimetric benefits of a deep inspiration breath-hold (DIBH) technique which has two distinct features - deep inspiration which reduces lung density and breath-hold which immobilizes lung tumors. Both properties can potentially reduce the mass of normal lung tissue in the high dose region, thus improving the possibility of dose escalation. Methods and Materials: To study the efficacy of the DIBH technique, CT scans are acquired for each patient under 4 respiration conditions: free-breathing; DIBH; shallow inspiration breath-hold; shallow expiration breath-hold. The free-breathing and DIBH scans are used to generate treatment plans for comparison of standard and DIBH techniques, while the shallow inspiration and expiration scans provide information on the maximum extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry and slow vital capacity maneuvers. For the treatment plan comparison free-breathing and DIBH planning target volumes (PTVs) are constructed consisting of the CTV plus a margin for setup error and lung tumor motion. For both plans the margin for setup error is the same while the margin for lung tumor motion differs. The margin for organ motion in free-breathing is determined by the maximum tumor excursions in the shallow inspiration and expiration CT scans. For the DIBH, tumor motion is reduced to the extent to which DIBH can be maintained and the margin for any residual tumor motion is determined from repeat fluoroscopic movies, acquired with the patient monitored using spirometry. Three-dimensional treatment plans, generated using apertures based on the free-breathing and DIBH PTVs, are

  19. Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise Reinert Ørsum; Poulsen, Thomas Tuxen; Poulsen, Hans Skovgaard

    2012-01-01

    Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated their exp......Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated...

  20. Impact of the planning CT scan time on the reflection of the lung tumor motion

    International Nuclear Information System (INIS)

    Kim, Su San; Choi, Eun Kyung; Yi, Byong Yong; Ha, Sung Whan

    2004-01-01

    To evaluate the reflection of tumor motion according to the planning CT scan time. A model of N-shape, which moved along the longitudinal axis during the ventilation caused by a mechanical ventilator, was produced. The model was scanned by planning CT, while setting the relative CT scan time (T; CT scan time/ventilatory period) to 0.33, 0.50, 0.67, 0.75, 1.00, 1.33 T, and 1.53 T. In addition, three patients with non-small cell lung cancer who received stereotactic radiosurgery in the Department of Radiation Oncology, Asan Medical Center from 03/19/2002 to 05/21/2002 were scanned. Slow (IQ Premier, Picker, scan time 2.0 seconds per slice) and fast CT scans (Light Speed, GE Medical System, with a scan time of 0.8 second per slice) were performed for each patient. The magnitude of reflected movement of the N-shaped model was evaluated by measuring the transverse length, which reflected the movement of the declined bar of the model at each slice. For patients' scans, all CT data sets were registered using a stereotactic body frame scale with the gross tumor volumes delineated in one CT image set. The volume and three-dimensional diameter of the gross tumor volume were measured and analyzed between the slow and fast CT scans. The reflection degree of longitudinal movement of the model increased in proportion to the relative CT scan times below 1.00 T, but remained constant above 1.00 T. Assuming the mean value of scanned transverse lengths with CT scan time 1.00 T to be 100%, CT scans with scan times of 0.33, 0.50, 0.67, and 0.75 T missed the tumor motion by 30, 27, 20, and 7.0% respectively. Slow (scan time 2.0 sec) and Fast (scan time 0.8 sec) CT scans of three patients with longitudinal movement of 3, 5, and 10 mm measured by fluoroscopy revealed the increases in the diameter along the longitudinal axis increased by 6.3, 17, and 23% in the slow CT scans. As the relative CT scan time increased, the reflection of the respiratory tumor movement on planning CT also

  1. Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

    International Nuclear Information System (INIS)

    Liu Juzhen; Cai Tietie; Qin Shana

    2007-01-01

    Objective: To investigate the diagnostic value of combined determination of serum NSE, CA242, tissue polypeptide antigen (TPA) and CEA levels in patients with primary lung cancer. Methods: Serum NSE, CA242, TPA and CEA levels were determined with ELISA in (1) 102 patients with various types of primary lung carcinoma (adenocarcinoma 38, squamous cell carcinoma 32, small cell lung carcinoma 32) (2) 33 patients with open lung T. B. and (3) 30 controls. Results: (1) In patients with lung cancer, serum levels of all the four markers were increased and significantly higher than their respective values in patients with open lung T.B. and controls. (2) Positive rate of combined any two markers were 75% for adenocarcinoma, 50% for squamous cell carcinoma and 65% for small cell lung carcinoma, while false positive rate was only 9% for T.B patients and none for the controls. (3) The most appropriate single marker for each specific type of lung cancer was: NSE for SCLC (sensitivity 72%, specificity 97%, CA242 for adenocarcinoma sensitivity 62%, specificity 90%). Conclusion: Combined determination of these tumor markers would improve the sensitivity and specificity for diagnosis of primary lung carcinoma. (authors)

  2. A Method to Automate the Segmentation of the GTV and ITV for Lung Tumors

    International Nuclear Information System (INIS)

    Ehler, Eric D.; Bzdusek, Karl; Tome, Wolfgang A.

    2009-01-01

    Four-dimensional computed tomography (4D-CT) is a useful tool in the treatment of tumors that undergo significant motion. To fully utilize 4D-CT motion information in the treatment of mobile tumors such as lung cancer, autosegmentation methods will need to be developed. Using autosegmentation tools in the Pinnacle 3 v8.1t treatment planning system, 6 anonymized 4D-CT data sets were contoured. Two test indices were developed that can be used to evaluate which autosegmentation tools to apply to a given gross tumor volume (GTV) region of interest (ROI). The 4D-CT data sets had various phase binning error levels ranging from 3% to 29%. The appropriate autosegmentation method (rigid translational image registration and deformable surface mesh) was determined to properly delineate the GTV in all of the 4D-CT phases for the 4D-CT data sets with binning errors of up to 15%. The ITV was defined by 2 methods: a mask of the GTV in all 4D-CT phases and the maximum intensity projection. The differences in centroid position and volume were compared with manual segmentation studies in literature. The indices developed in this study, along with the autosegmentation tools in the treatment planning system, were able to automatically segment the GTV in the four 4D-CTs with phase binning errors of up to 15%.

  3. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jun-Hai; Zhao, Chun-Liu [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China); Ding, Lan-Bao [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Zhou, Xi, E-mail: modelmap@139.com [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China)

    2015-10-09

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  4. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yan, Jun-Hai; Zhao, Chun-Liu; Ding, Lan-Bao; Zhou, Xi

    2015-01-01

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  5. Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

    2011-01-01

    Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

  6. SU-E-T-638: Proton Beam Delivery to a Moving Lung Tumor and Monte Carlo Simulation with TOPAS

    Energy Technology Data Exchange (ETDEWEB)

    Coruh, M; Ewell, L [Hampton University, Hampton, Virginia (United States); Demez, N [Hampton University Proton Therapy Institute, Hampton, VA (United States)

    2015-06-15

    Purpose: To estimate the dose delivered to a moving lung tumor by proton therapy beams of different modulation types, and compare with Monte Carlo predictions. Methods: A radiology support devices (RSD) phantom was irradiated with therapeutic proton radiation beams using two different types of modulation: uniform scanning (US) and double scattered (DS). The Eclipse© dose plan was designed to deliver 1.00Gy to the isocenter of a static ∼3×3×3cm (27cc) tumor in the phantom with 100% coverage. The peak to peak amplitude of tumor motion varied from 0.0 to 2.5cm. The radiation dose was measured with an ion-chamber (CC-13) located within the tumor. The time required to deliver the radiation dose varied from an average of 65s for the DS beams to an average of 95s for the US beams. Results: The amount of radiation dose varied from 100% (both US and DS) to the static tumor down to approximately 92% for the moving tumor. The ratio of US dose to DS dose ranged from approximately 1.01 for the static tumor, down to 0.99 for the 2.5cm moving tumor. A Monte Carlo simulation using TOPAS included a lung tumor with 4.0cm of peak to peak motion. In this simulation, the dose received by the tumor varied by ∼40% as the period of this motion varied from 1s to 4s. Conclusion: The radiation dose deposited to a moving tumor was less than for a static tumor, as expected. At large (2.5cm) amplitudes, the DS proton beams gave a dose closer to the desired dose than the US beams, but equal within experimental uncertainty. TOPAS Monte Carlo simulation can give insight into the moving tumor — dose relationship. This work was supported in part by the Philips corporation.

  7. Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Le Teuff, Gwénaël; Marguet, Sophie; Lantuejoul, Sylvie; Dunant, Ariane; Graziano, Stephen; Pirker, Robert; Douillard, Jean-Yves; Le Chevalier, Thierry; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Popper, Helmut; Soria, Jean-Charles; Shepherd, Frances A.; Seymour, Lesley; Tsao, Ming Sound

    2016-01-01

    Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer. PMID:26834066

  8. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.

    Science.gov (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai

    2008-10-01

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (PPokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). There was high expression of Pokemon in NSCLC

  9. Prognostic value of tumor-to-blood standardized uptake ratio in patients with resectable non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Seung Hyeon; Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan(Korea, Republic of); Kim, Bum Soo; Kim, Seong Jang [Dept. of Nuclear Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-09-15

    Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUVmax). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.

  10. Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer.

    Science.gov (United States)

    Saghaeian Jazi, Marie; Samaei, Nader Mansour; Ghanei, Mostafa; Shadmehr, Mohammad Behgam; Mowla, Seyed Javad

    2016-08-01

    Despite the advances in cancer therapy, lung cancer still remains the most leading cause of cancer death worldwide. The long non-coding RNAs (lncRNAs) are recently introduced as novel regulators of human cancers. SOX2 overlapping transcript (SOX2OT) is a cancer-associated lncRNA gene that encodes different alternatively spliced transcripts. Here, we investigated the alterations in the preferential expression of different SOX2OTs in twenty non-small cell lung cancer (NSCLC) patients by real-time quantitative reverse transcription PCR (qRT-PCR) method. We observed preferential expression of SOX2OT4 and SOX2OT7 in lung tumor tissues. The quantitative gene expression analysis revealed that >30 % of NSCLC tumors express SOX2OT4 (mean = 7.6 times) and SOX2OT7 (mean = 5.9 times) more than normal tissues, with higher expression in squamous cell carcinoma. Further, we observed overexpression of pluripotency-associated transcription factor, SOX2 in 47 % of our samples concordant with SOX2OT (R = 0.62, P value in 36.8 % of tumor tissues. Then, we investigated the effects of SOX2OT suppression in lung adenocarcinoma cell line, by means of RNAi. Cell characteristics of colony formation, apoptosis, 2-D mobility, and cell cycle progression were measured in control and treated A549 cells. The SOX2OT knockdown significantly reduced the colony formation ability of cancer cells; however, no alterations in the rate of apoptosis were detected. On the other hand, SOX2OT-suppressed cells had elevated accumulation in G2/M phase of cell cycle and exhibited limited mobility. Altogether, our findings support a potential oncogenic role for SOX2OT in non-small cell lung cancer tumor genesis and SOX2OT seems a promising therapeutic candidate for NSCLC.

  11. Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation.

    Science.gov (United States)

    Peppoloni, S; Herberman, R B; Gorelik, E

    1985-06-01

    This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated "tum-" (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth. In an in vitro cytotoxic assay, spleen cells after in vivo and in vitro immunization with tum- clones demonstrated high cytotoxic activity against various tum+ clones and parental 3LL cells, as well as against tum- clones. In addition, parental 3LL tumor cells and tum- cells were similarly able to inhibit

  12. Assessing tumor treatment response and prognosis in non-small cell lung cancer with perfusion CT

    International Nuclear Information System (INIS)

    Wang Jianwei; Wu Ning; Song Ying

    2010-01-01

    Objective: To prospectively investigate whether any of the perfusion parameters would predict early tumor response to chemotherapy and/or radiotherapy and prognosis in non-small cell lung cancer (NSCLC). Methods: In a prospective series, Perfusion CT were performed in 152 patients suspected lung cancer with 16-slice or 8-slice multislice CT. Contrast medium (50 ml) was injected at a rate of 4 ml/s with a power injector. The scanning delay was 10 seconds and the scanning time was 50 seconds. Among 152 patients, 123 patients were proved lung cancer by pathology. With the perfusion 3.0 software, the parameters including blood flow (BF), blood volume (BV), mean transit time (MTT) and capillary permeability surface area product (PS) were calculated. The perfusion image quality was evaluated on a 4-1eveal scale. The treatment response after chemotherapy and (or) radiotherapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST), and then the relationship between perfusion parameters with early tumor response to chemotherapy and (or) radiotherapy was evaluated. Student t test and Kaplan-Meier estimates were used for data analysis. Results: In 84 patients (68.3%), the perfusion image quality was staged level 2 (moderate) and level 3 (good). Among them, 35 patients with NSCLC were assessed with RECIST after chemotherapy and (or) radiotherapy. In these 35 patients, The BF of responders and nonresponders was (81.0 ± 33.6)and (56.3 ± 23.1) ml · min -1 ·100 g -1 , respectively, which was significantly different(t=2.393, P=0.023). The median PFS of low-BF group (BF ≤ 80 ml · min -1 · 100 g -1 ) and high-BF group (BF>80 ml · min -1 · 100 g -1 ) was 11.8 and 8.0 months respectively (P>0.05), and the median PFS of low-BV group (BF ≤ 6 ml/100 g -1 ) and high-BV group (BF>6 ml/100 g -1 ) was 9.2 and 8.0 months respectively(P>0.05), both of them were not significantly different. Conclusion: NSCLC in high perfusion are relatively sensitive to chemotherapy

  13. INDUCTION OF DNA ADDUCTS, TUMORS, AND KI-RAS ONCOGENE MUTATIONS IN STRAIN A/J MOUSE LUNG BY IP. ADMINISTRATION OF DIBENZ[A,H]ANTHRACENE

    Science.gov (United States)

    Induction of DNA adducts, tumors, and Ki-ras oncogene mutations in strain AlJ mouse lung by ip. administration of dibenz[a,h]anthracene Previous studies of polycyclic aromatic hydrocarbon (P AH) induced lung tumors in the strain NJ mouse model system have demonstrated qua...

  14. Differential effects of drugs targeting cancer stem cell (CSC and non-CSC populations on lung primary tumors and metastasis.

    Directory of Open Access Journals (Sweden)

    Leyre Larzabal

    Full Text Available Cancer stem cells (CSCs are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05, whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05. Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster

  15. SU-E-J-236: Audiovisual Biofeedback Improves Breath-Hold Lung Tumor Position Reproducibility Measured with 4D MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D; Pollock, S; Keall, P [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, NSW (Australia); Greer, P [School of Mathematical and Physical Sciences, The University of Newcastle, Newcastle, NSW (Australia); Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Lapuz, C; Ludbrook, J [Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Kim, T [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, NSW (Australia); Department of Radiation Oncology, University of Virginia Health System, Charlottesville, VA (United States)

    2015-06-15

    Purpose: Audiovisual biofeedback breath-hold (AVBH) was employed to reproduce tumor position on inhale and exhale breath-holds for 4D tumor information. We hypothesize that lung tumor position will be more consistent using AVBH compared with conventional breath-hold (CBH). Methods: Lung tumor positions were determined for seven lung cancer patients (age: 25 – 74) during to two separate 3T MRI sessions. A breathhold training session was performed prior to the MRI sessions to allow patients to become comfortable with AVBH and their exhale and inhale target positions. CBH and AVBH 4D image datasets were obtained in the first MRI session (pre-treatment) and the second MRI session (midtreatment) within six weeks of the first session. Audio-instruction (MRI: Siemens Skyra) in CBH and verbal-instruction (radiographer) in AVBH were used. A radiation oncologist contoured the lung tumor using Eclipse (Varian Medical Systems); tumor position was quantified as the centroid of the contoured tumor after rigid registration based on vertebral anatomy across two MRI sessions. CBH and AVBH were compared in terms of the reproducibility assessed via (1) the difference between the two exhale positions for the two sessions and the two inhale positions for the sessions. (2) The difference in amplitude (exhale to inhale) between the two sessions. Results: Compared to CBH, AVBH improved the reproducibility of two exhale (or inhale) lung tumor positions relative to each other by 33%, from 6.4±5.3 mm to 4.3±3.0 mm (p=0.005). Compared to CBH, AVBH improved the reproducibility of exhale and inhale amplitude by 66%, from 5.6±5.9 mm to 1.9±1.4 mm (p=0.005). Conclusions: This study demonstrated that audiovisual biofeedback can be utilized for improving the reproducibility of breath-hold lung tumor position. These results are advantageous towards achieving more accurate emerging radiation treatment planning methods, in addition to imaging and treatment modalities utilizing breath

  16. SU-E-J-236: Audiovisual Biofeedback Improves Breath-Hold Lung Tumor Position Reproducibility Measured with 4D MRI

    International Nuclear Information System (INIS)

    Lee, D; Pollock, S; Keall, P; Greer, P; Lapuz, C; Ludbrook, J; Kim, T

    2015-01-01

    Purpose: Audiovisual biofeedback breath-hold (AVBH) was employed to reproduce tumor position on inhale and exhale breath-holds for 4D tumor information. We hypothesize that lung tumor position will be more consistent using AVBH compared with conventional breath-hold (CBH). Methods: Lung tumor positions were determined for seven lung cancer patients (age: 25 – 74) during to two separate 3T MRI sessions. A breathhold training session was performed prior to the MRI sessions to allow patients to become comfortable with AVBH and their exhale and inhale target positions. CBH and AVBH 4D image datasets were obtained in the first MRI session (pre-treatment) and the second MRI session (midtreatment) within six weeks of the first session. Audio-instruction (MRI: Siemens Skyra) in CBH and verbal-instruction (radiographer) in AVBH were used. A radiation oncologist contoured the lung tumor using Eclipse (Varian Medical Systems); tumor position was quantified as the centroid of the contoured tumor after rigid registration based on vertebral anatomy across two MRI sessions. CBH and AVBH were compared in terms of the reproducibility assessed via (1) the difference between the two exhale positions for the two sessions and the two inhale positions for the sessions. (2) The difference in amplitude (exhale to inhale) between the two sessions. Results: Compared to CBH, AVBH improved the reproducibility of two exhale (or inhale) lung tumor positions relative to each other by 33%, from 6.4±5.3 mm to 4.3±3.0 mm (p=0.005). Compared to CBH, AVBH improved the reproducibility of exhale and inhale amplitude by 66%, from 5.6±5.9 mm to 1.9±1.4 mm (p=0.005). Conclusions: This study demonstrated that audiovisual biofeedback can be utilized for improving the reproducibility of breath-hold lung tumor position. These results are advantageous towards achieving more accurate emerging radiation treatment planning methods, in addition to imaging and treatment modalities utilizing breath

  17. MiR-564 functions as a tumor suppressor in human lung cancer by targeting ZIC3

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bin [Department of Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Jia, Lin [Department of Nephrology, The Central Hospital of Wuhan, Wuhan, Hubei 430079 (China); Guo, Qiaojuan [Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, Fujian 350000 (China); Ren, Hui; Hu, Desheng; Zhou, Xiaoyi; Ren, Qingrong [Department of Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Hu, Yanping, E-mail: huyp1989@163.com [Department of Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Xie, Tao, E-mail: xietao930@hotmail.com [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China)

    2015-11-27

    Although miR-564 was reported to be dysregulated in human malignancy, the function and mechanism of miR-564 in tumorigenesis remains unknown. In the present study, we found that miR-564 frequently downregulated in lung cancer cells and significantly inhibited cell proliferation, cell cycle progression, motility, and the tumorigenicity of lung cancer cells. Moreover, we identified zic family member 3 (ZIC3) as a direct target of miR-564. ZIC3 overexpression impaired the suppressive effects of miR-564 on the capacity of lung cancer cells for proliferation and motility. Finally, we detected the expression level of miR-564 and ZIC3 protein in tissue specimens, and found a significant negative correlation between them. Patients with low levels of miR-564 showed a poorer overall survival. Taken together, our present study revealed the tumor suppressor role of miR-564, indicating restoration of miR-564 as a potential therapeutic strategy for the treatment of lung cancer. - Highlights: • MiR-564 inhibits cancer cell proliferation, cell cycle progression, migration, and invasion. • miR-564 suppresses the tumorigenicity of lung cancer cell in vivo. • ZIC3 is a direct and functional target of miR-564. • The expression of miR-564 was negatively correlated with ZIC3 protein in tumors. • Both low miR-564 and high ZIC3 was associated with tumor stage and prognosis.

  18. Tumor biomarker testing in non-small-cell lung cancer: A decade of change.

    Science.gov (United States)

    VanderLaan, Paul A; Rangachari, Deepa; Majid, Adnan; Parikh, Mihir S; Gangadharan, Sidharta P; Kent, Michael S; McDonald, Danielle C; Huberman, Mark S; Kobayashi, Susumu S; Costa, Daniel B

    2018-02-01

    Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics. The majority of 1009 NSCLC patients had advanced stages of adenocarcinoma with most tissues obtained from the lung, mediastinal/hilar nodes, or pleura. The majority of testing was performed on cytology or small biopsy specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing at our institution for EGFR, ALK, ROS1 and PD-L1 all occurred within the first year following evidence of clinical activity or regulatory body approval of an associated inhibitor. The overall testing failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene identified (EGFR/ALK/ROS1/BRAF V600E) with an approved oral targeted therapy, with the highest prevalence in those patients with no or light (≤15 pack-years) history of tobacco use. Tumor biomarker testing using clinical NSCLC specimens in routine oncologic care evolves rapidly following approval of targeted therapies linked to diagnostic assays. Our practice's decade plus experience highlights the rapid evolution of biomarker testing and confirms the therapeutic relevance of such testing in all patients-particularly those patients with light/no history of tobacco use. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Doranidazole (PR-350), a hypoxic cell radiosensitizer, radiosensitizes human lung tumors (RERF-LC- AI) and causes changes in tumor oxygenation

    International Nuclear Information System (INIS)

    Kubota, N.; Griffin, R.J.; Williams, B.W.; Song, C.W.; Yahiro, T.

    2003-01-01

    Full text: We previously have reported the radiosensitizing capability of Doranidazole (PR-350) on SCCVII cells and tumors (Puerto Rico, 2001). In the present study, we have investigated the efficacy of PR-350 as a hypoxic cell radiosensitizer using human lung cancer cells (RERF-LC-AI) in vitro and also RERF-LC-AI tumors grown s.c. in Balb/c nude mice. Using the micronucleus assay method, we determined the effect of PR-350 on the response of RERF-LC-AI cells to radiation under hypoxic conditions and enhancement ratios (ER) of 1.45∼2.26 were obtained. The in vivo radiosensitizing effect was studied by irradiating RERF-LC-AI tumors with 15 Gy at 20 min. after i.v. injection of PR-350 (200mg/kg) and measuring the tumor growth delay. Significant growth delay occurred after i.v. injection of PR-350 before irradiation compared to radiation alone. We measured tumor pO 2 at 3, 7 and 14 days after treatment using an Eppendorf pO 2 histograph. The frequency of pO 2 values 2 in tumors treated with radiation plus PR-350 were higher than that in tumors treated with radiation plus saline. These data suggest that the O 2 consumption in tumors treated with radiation plus PR-350 was less than that in tumors treated with radiation plus saline due to greater drug and radiation-induced cell death. This hypothesis is supported by the fact that the tumor size in the combined treatment group was smaller than in radiation alone. These results suggest that PR-350 may improve the response of tumors to radiotherapy not only by increasing the radiosensitivity of hypoxic cells but also by improving tumor oxygenation over many days during fractionated radiotherapy

  20. A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Kadota, Kyuichi; Miyai, Yumi; Katsuki, Naomi; Kushida, Yoshio; Matsunaga, Toru; Okuda, Masaya; Yokomise, Hiroyasu; Kanaji, Nobuhiro; Bandoh, Shuji; Haba, Reiji

    2017-06-01

    For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

  1. Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells

    NARCIS (Netherlands)

    K. Leithner (Katharina); C. Wohlkoenig (Christoph); E. Stacher (Elvira); J. Lindenmann (Jörg); N.A. Hofmann (Nicole); B. Gallé (Birgit); C. Guelly (Christian); F. Quehenberger (Franz); P. Stiegler (Philipp); F.-M. Smolle-Jüttner (Freyja-Maria); J.N.J. Philipsen (Sjaak); H.H. Popper (Helmut); A. Hrzenjak (Andelko); A. Olschewski (Andrea); H. Olschewski (Horst)

    2014-01-01

    textabstractBackground: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung

  2. Overexpression of the p53 tumor suppressor gene product in primary lung adenocarcinomas is associated with cigarette smoking

    NARCIS (Netherlands)

    Westra, W. H.; Offerhaus, G. J.; Goodman, S. N.; Slebos, R. J.; Polak, M.; Baas, I. O.; Rodenhuis, S.; Hruban, R. H.

    1993-01-01

    Mutations in the p53 tumor suppressor gene are frequently observed in primary lung adenocarcinomas, suggesting that these mutations are critical events in the malignant transformation of airway cells. These mutations are often associated with stabilization of the p53 gene product, resulting in the

  3. Rapid Diagnosis of Lung Tumors, a Feasability Study Using Maldi-Tof Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Geoffrey Brioude

    Full Text Available Despite recent advances in imaging and core or endoscopic biopsies, a percentage of patients have a major lung resection without diagnosis. We aimed to assess the feasibility of a rapid tissue preparation/analysis to discriminate cancerous from non-cancerous lung tissue.Fresh sample preparations were analyzed with the Microflex LTTM MALDI-TOF analyzer. Each main reference spectra (MSP was consecutively included in a database. After definitive pathological diagnosis, each MSP was labeled as either cancerous or non-cancerous (normal, inflammatory, infectious nodules. A strategy was constructed based on the number of concordant responses of a mass spectrometry scoring algorithm. A 3-step evaluation included an internal and blind validation of a preliminary database (n = 182 reference spectra from the 100 first patients, followed by validation on a whole cohort database (n = 300 reference spectra from 159 patients. Diagnostic performance indicators were calculated.127 cancerous and 173 non-cancerous samples (144 peripheral biopsies and 29 inflammatory or infectious lesions were processed within 30 minutes after biopsy sampling. At the most discriminatory level, the samples were correctly classified with a sensitivity, specificity and global accuracy of 92.1%, 97.1% and 95%, respectively.The feasibility of rapid MALDI-TOF analysis, coupled with a very simple lung preparation procedure, appears promising and should be tested in several surgical settings where rapid on-site evaluation of abnormal tissue is required. In the operating room, it appears promising in case of tumors with an uncertain preoperative diagnosis and should be tested as a complementary approach to frozen-biopsy analysis.

  4. Neuroendocrine tumors of the lung: major radiologic findings in a series of 22 histopathologically confirmed cases

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam, E-mail: marcelk46@yahoo.com.br [Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP), SP (Brazil); Department of Diagnostic and Interventional Radiology, Heidelberg University (Germany); Barreto, Andre Rodrigues Facanha [Clinica Radius, Clinica Sao Carlos Imagem and Santa Casa de Misericordia de Fortaleza, Fortaleza, CE (Brazil); Chagas Neto, Francisco Abaete [Program of Health Sciences Applied to the Locomotor System - Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, SP (Brazil); Muglia, Valdair Francisco; Elias Junior, Jorge [Division of Radiology, Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRPUSP), Ribeirao Preto, SP (Brazil)

    2012-07-15

    Objective: To describe key imaging findings in a series of cases of primary neuroendocrine tumors of the lung (NTLs), with emphasis on computed tomography changes. Materials And Methods: Imaging studies of 22 patients (12 men, mean age 60 years) with histopathologically confirmed diagnosis, evaluated in the author's institution during the last five years were retrospectively reviewed by two radiologists, with findings being consensually described focusing on changes observed at computed tomography. Results: The authors have described five typical carcinoids, three atypical carcinoids, three large-cell neuroendocrine carcinomas (LCNCs), and 11 small-cell lung cancers (SCLCs). Only one typical carcinoid presented the characteristic appearance of central endobronchial nodule with distal pulmonary atelectasis, while the others were pulmonary nodules or masses. The atypical carcinoids corresponded to peripheral heterogeneous masses. One out of the three LCNCs was a peripheral homogeneous mass, while the others were ill-defined and heterogeneous. The 11 SCLCs corresponded to central, infiltrating and heterogeneous masses with secondary pleuropulmonary changes. Calcifications were absent both in LGNCs and SCLCs. Metastases were found initially and also at follow-up of all the cases of LCNCs and SCLCs. Conclusion: Although some imaging features may be similar, radiologic findings considered together with clinical information may play a relevant role in the differentiation of histological types of NTLs. (author)

  5. Tumor necrosis factor-α induced protein 6 attenuates acute lung injury following paraquat exposure.

    Science.gov (United States)

    Xu, Jiajun; Zhen, Jiantao; Zhu, Jingfa; Lin, Qingming

    2016-01-01

    Paraquat exposure commonly occurs in the developing countries and the mortality rate is high. However, there is currently no consensus on the efficacy of treatment for paraquat exposure. The study was aimed to explore the effects of tumor necrosis factor-α (TNF-α) induced protein 6 (TSG-6) on acute lung injury (ALI) following paraquat exposure in rats. Male Sprague-Dawley (SD) rats were randomly divided into the sham group (n = 8), the paraquat group (n = 8), and the paraquat TSG-6-treated group (n = 8). Rats were administered with 50 mg/kg of paraquat intraperitoneally. At 1 h after exposure, rats were treated with 30 μg of recombinant human TSG-6 (rhTSG-6) intraperitoneally. After 6 h of exposure, ALI scores were evaluated by histology and the expression of pro-inflammatory cytokines in lung was assayed using real-time RT-PCR. ALI scores were significantly lower in the paraquat TSG-6-treated group, compared with the paraquat group (p paraquat TSG-6-treated group, compared with the paraquat group (p paraquat exposure by suppressing inflammatory response.

  6. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

    Science.gov (United States)

    Pan, Y W; Zhou, Z G; Wang, M; Dong, J Q; Du, K P; Li, S; Liu, Y L; Lv, P J; Gao, J B

    2016-11-03

    Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

  7. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex.

    Science.gov (United States)

    Zhang, Wenjing; Gao, Yijun; Li, Peixue; Shi, Zhubing; Guo, Tong; Li, Fei; Han, Xiangkun; Feng, Yan; Zheng, Chao; Wang, Zuoyun; Li, Fuming; Chen, Haiquan; Zhou, Zhaocai; Zhang, Lei; Ji, Hongbin

    2014-03-01

    Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality. Hippo (Hpo) pathway is a conserved regulator of organ size in both Drosophila and mammals. Emerging evidence has suggested the significance of Hpo pathway in cancer development. In this study, we identify VGLL4 as a novel tumor suppressor in lung carcinogenesis through negatively regulating the formation of YAP-TEAD complex, the core component of Hpo pathway. Our data show that VGLL4 is frequently observed to be lowly expressed in both mouse and human lung cancer specimens. Ectopic expression of VGLL4 significantly suppresses the growth of lung cancer cells in vitro. More importantly, VGLL4 significantly inhibits lung cancer progression in de novo mouse model. We further find that VGLL4 inhibits the activity of the YAP-TEAD transcriptional complex. Our data show that VGLL4 directly competes with YAP in binding to TEADs and executes its growth-inhibitory function through two TDU domains. Collectively, our study demonstrates that VGLL4 is a novel tumor suppressor for lung cancer through negatively regulating the YAP-TEAD complex formation and thus the Hpo pathway.

  8. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

    International Nuclear Information System (INIS)

    Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

    2007-01-01

    Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

  9. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

    2015-01-01

    , decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts......BACKGROUND: The tumor microenvironment plays a determinative role in stimulating tumor progression and metastasis. Notably, tumor-stroma signals affect the pattern of infiltrated immune cells and the profile of tumor-released cytokines. Among the known molecules that are engaged in stimulating...... the metastatic spread of tumor cells is the S100A4 protein. S100A4 is known as an inducer of inflammatory processes and has been shown to attract T-cells to the primary tumor and to the pre-metastatic niche. The present study aims to examine the immunomodulatory role of S100A4 in vivo and in vitro and assess...

  10. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  11. Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implication on Anti-Tumor Immunity in Lung Cancer

    Science.gov (United States)

    Herrmann, Amanda C.; Bernatchez, Chantale; Haymaker, Cara; Molldrem, Jeffrey J.; Hong, Waun Ki; Perez-Soler, Roman

    2016-01-01

    Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity. Erlotinib up-regulated MHC-I and MHC-II proteins on IFNγ treated keratinocytes but abrogated IFNγ-induced expression of PD-L1, suggesting the potential role of infiltrating autoreactive T cells in the damage of keratinocytes in affected skin. Interestingly, the surface expression of MHC-I, MHC-II, and PD-L1 was up-regulated in response to IFNγ more often in lung cancer cell lines sensitive to erlotinib, but only expression of PD-L1 was inhibited by erlotinib. Further, erlotinib significantly increased T cell mediated cytotoxicity on lung cancer cells. Lastly, the analysis of gene expression dataset of 186 lung cancer cell lines from Cancer Cell Line Encyclopedia demonstrated that overexpression of PD-L1 was associated with sensitivity to erlotinib and higher expression of genes related to antigen presenting pathways and IFNγ signaling pathway. Our findings suggest that the EGFR inhibitors can facilitate anti-tumor adaptive immune responses by breaking tolerance especially in EGFR driven lung cancer that are associated with overexpression of PD-L1 and genes related to antigen presentation and inflammation. PMID:27467256

  12. Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implication on Anti-Tumor Immunity in Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Jin S Im

    Full Text Available Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity. Erlotinib up-regulated MHC-I and MHC-II proteins on IFNγ treated keratinocytes but abrogated IFNγ-induced expression of PD-L1, suggesting the potential role of infiltrating autoreactive T cells in the damage of keratinocytes in affected skin. Interestingly, the surface expression of MHC-I, MHC-II, and PD-L1 was up-regulated in response to IFNγ more often in lung cancer cell lines sensitive to erlotinib, but only expression of PD-L1 was inhibited by erlotinib. Further, erlotinib significantly increased T cell mediated cytotoxicity on lung cancer cells. Lastly, the analysis of gene expression dataset of 186 lung cancer cell lines from Cancer Cell Line Encyclopedia demonstrated that overexpression of PD-L1 was associated with sensitivity to erlotinib and higher expression of genes related to antigen presenting pathways and IFNγ signaling pathway. Our findings suggest that the EGFR inhibitors can facilitate anti-tumor adaptive immune responses by breaking tolerance especially in EGFR driven lung cancer that are associated with overexpression of PD-L1 and genes related to antigen presentation and inflammation.

  13. Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

    International Nuclear Information System (INIS)

    Kolesnichenko, T.S.; Gor'kova, T.G.

    1985-01-01

    Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

  14. Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea.

    Science.gov (United States)

    Campillo, Noelia; Torres, Marta; Vilaseca, Antoni; Nonaka, Paula Naomi; Gozal, David; Roca-Ferrer, Jordi; Picado, César; Montserrat, Josep Maria; Farré, Ramon; Navajas, Daniel; Almendros, Isaac

    2017-03-16

    An adverse role for obstructive sleep apnea (OSA) in cancer epidemiology and outcomes has recently emerged from clinical and animal studies. In animals, intermittent hypoxia (IH) mimicking OSA promotes tumor malignancy both directly and via host immune alterations. We hypothesized that IH could potentiate cancer aggressiveness through activation of the cyclooxygenase-2 (COX-2) pathway and the concomitant increases in prostaglandin E2 (PGE 2 ). The contribution of the COX-2 in IH-induced enhanced tumor malignancy was assessed using celecoxib as a COX-2 specific inhibitor in a murine model of OSA bearing Lewis lung carcinoma (LLC1) tumors. Exposures to IH accelerated tumor progression with a tumor associated macrophages (TAMs) shift towards a pro-tumoral M2 phenotype. Treatment with celecoxib prevented IH-induced adverse tumor outcomes by inhibiting IH-induced M2 polarization of TAMs. Furthermore, TAMs isolated from IH-exposed mice treated with celecoxib reduced the proliferation of LLC1 naïve cells, while the opposite occurred with placebo-treated IH-exposed mice. Finally, in vitro IH exposures of murine macrophages and LLC1 cells showed that both cell types increased PGE 2 release in response to IH. These results suggest a crucial role for the COX-2 signaling pathway in the IH-exacerbated malignant processes, and designate macrophages and lung adenocarcinoma cells, as potential sources of PGE 2 .

  15. Tumor Associated Fibroblasts Promote PD-L1 Expression in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Haiyang HE

    2017-05-01

    Full Text Available Background and objective Tumor-associated fibroblasts (TAF is an important part of TME, which inhibits the function of immune cells. CD8+ T cells play a significant role in tumor immunity. T-cell membrane possesses a distinct type of molecule with a negative regulatory function. Upon interaction with its corresponding ligand [programmed death factor ligand 1 (PD-L1], programmed death factor 1 (PD-1 is activated and thus inhibits the kinase activity of T cells. This study aims to explore the possible effects of TAF on PD-L1 expression in lung cancer cells. Methods Lung cancer cell lines H1975 and H520 were co-cultured with (experiment or without TAF (control via Transwell assay for through 48 hours under the same culture condition. H1975 and H520 cells were counted using a microscope. The protein and mRNA expression levels of PD-L1 were detected by FCM assay and PCR analysis, respectively. Results The numbers of lung cancer cells in 100 μm2 for H1975 and H520 cells are (46±21 and (38±10 in the experiment group, respectively, and (16±5 and (12±5 in the control group, respectively (P<0.05. The expression levels of the PD-L1 protein in H1975 and H520 cells are (20.93%±3.54% and (19.26%±3.04% in the experiment group, respectively, and (12.58%±2.52% and (11.60%±2.65% in the control group, respectively (P<0.05. The mRNA expression levels in H1975 and H520 cells are (16.45±1.25 and (15.38±2.02 pg/mL in the experiment group, respectively, and (7.78±1.27 and (7.20±1.58 pg/mL (P<0.05 in the control group, respectively (P<0.05. Conclusion TAF promotes the growth and increases the expression of PD-L1 in H1975 and H520 cells.

  16. Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors

    International Nuclear Information System (INIS)

    Kitahashi, Tsukasa; Takahashi, Mami; Yamada, Yutaka

    2008-01-01

    Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in exons 18 and 21 (4/12, 33%), but no activating mutation of K-ras was detected. In addition, one and four silent mutations were identified in K-ras (exon 1) and Egfr (exons 18, 20 and 21), respectively. Most mutations in both Egfr and K-ras were G/C→A/T transitions (7/8, 88% and 31/34, 91%, respectively). Although, the mutational patterns in equivalent human lesions were not completely coincident, this first report of Egfr mutations in an experimental lung tumor model suggests that X-rays or other factors producing oxygen radicals could cause EGFR mutations in some proportion of lung cancers in humans. (author)

  17. v-Ha-ras oncogene insertion: A model for tumor progression of human small cell lung cancer

    International Nuclear Information System (INIS)

    Mabry, M.; Nakagawa, Toshitaro; Nelkin, B.D.; McDowell, E.; Gesell, M.; Eggleston, J.C.; Casero, R.A. Jr.; Baylin, S.B.

    1988-01-01

    Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed classic SCLC lines, have properties similar to SCLC tumors in patients. To delineate further the relationships between these phenotypes and the molecular events involved, the authors inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The finding provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types

  18. Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

    Science.gov (United States)

    Hayashi, Kazuhiko; Yamamoto, Naoyoshi; Karube, Masataka; Nakajima, Mio; Tsuji, Hiroshi; Ogawa, Kazuhiko; Kamada, Tadashi

    2018-03-02

    Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. [Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats]. Progress report

    International Nuclear Information System (INIS)

    Moolgavkar, S.H.

    1994-01-01

    During the past several years, the authors have made considerable progress in modeling carcinogenesis in general, and in modeling radiation carcinogenesis, in particular. They present an overview of their progress in developing stochastic carcinogenesis models and applying them to experimental and epidemiologic data sets. Traditionally, cancer models have been used for the analysis of incidence (or prevalence) data in epidemiology and time to tumor data in experimental studies. The relevant quantities for the analysis of these data are the hazard function and the probability of tumor. The derivation of these quantities is briefly described here. More recently, the authors began to use these models for the analysis of data on intermediate lesions on the pathway to cancer. Such data are available in experimental carcinogenesis studies, in particular in initiation and promotion studies on the mouse skin and the rat liver. If however, quantitative information on intermediate lesions on the pathway to lung cancer were to be come available at some future date, the methods that they have developed for the analysis of initiation-promotion experiments could easily be applied to the analysis of these lesions. The mathematical derivations here are couched in terms of a particular two-mutation model of carcinogenesis. Extension to models postulating more than two mutations is not always straightforward

  20. Effect of radiation on the expression of tumor-associated antigens of human lung adenocarcinoma cells

    International Nuclear Information System (INIS)

    Hareyama, Masato

    1988-01-01

    We studied the effects of irradiation on the expression of a tumor-associated antigen (YH206 antigen) of cultured human lung adenocarcinoma A549 cells by using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. YH206 antigen is preferentially expressed on adenocarcinoma cells. Irradiation of A549 cells remarkably increased the expression of YH206 antigen on the cell surface and the level of the antigen in the culture supernatant as well as in the cell lysate, whereas it significantly affected the expression of HLA (MHC-class I) antigen on the same cells. The expression of HLA antigen on the cell was also increased after treatment of the cells with interferon-γ. In an additional experiment, cells were stained simultaneously for surface antigens (fluorescein coupled antibodies) and for DNA content (propidium iodide), and then dual parameter measurements were performed by flow cytometry to analyse the relationship between antigen levels and the cell cycle. YH206 antigen and HLA antigen increased more in the S and G 2 /M phases of the cell cycle than in G 0 /G 1 . The expression of YH206 antigen was enhanced in the S and G 2 /M phases by irradiation, whereas the expression of HLA antigen was enhanced in each phase of the cell cycle with irradiation or IFN. These results suggest that irradiation plays a key role in the change of the expression of certain tumor-associated antigens. (author)

  1. Studies in a Rat Lung Tumor Model: Cellular Biochemistry and Cytogenetics

    Science.gov (United States)

    1983-08-01

    returned to control levels at times when lung enzymes were still well above controls. This result suggests that xenobiotics reaching the lung via the...such effect, either in the lung or liver. This lung-specific enzyme induction by 2-NN is unusual, since most xenobiotics induce activity primarily in the...3 H-BaP by Lung and Liver Microsomes from MCA-- meated Rats After a single Intratracheal inoculation with 1.0 mg MCA the enzyme activity in lung

  2. Aberrant Promoter Methylation of p16 and MGMT Genes in Lung Tumors from Smoking and Never-Smoking Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2006-01-01

    Full Text Available Aberrant methylation in gene promoter regions leads to transcriptional inactivation of cancer-related genes and plays an integral role in tumorigenesis. This alteration has been investigated in lung tumors primarily from smokers, whereas only a few studies involved never-smokers. Here, we applied methylation-specific polymerase chain reaction to compare the frequencies of the methylated promoter of p16 and O6-methylguanine-DNA methyltransferase (MGMT genes in lung tumors from 122 patients with non-small cell lung cancer, including 81 smokers and 41 never-smokers. Overall, promoter methylation was detected in 52.5% (64 of 122 and 30.3°/a (37 of 122 of the p16 and MGMT genes, respectively. Furthermore, the frequency of promoter methylation was significantly higher among smokers, compared with never-smokers, for both the p16 [odds ratio (OR = 3.28; 95% confidence interval (CI = 1.28-8.39; P = .013] and MGMT (OR = 3.93; 95% CI =1.27-12.21; P = .018 genes. The trend for a higher promoter methylation frequency of these genes was also observed among female smokers compared with female never-smokers. Our results suggest an association between tobacco smoking and an increased incidence of aberrant promoter methylation of the p16 and MGMT genes in non-small cell lung cancer.

  3. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    of peritumoral brain edema (p tumors (p = 0.019), in younger patients (= 50 years) (p = 0.042), and in females (p = 0.016). The time to development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain......Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p

  4. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Baba, Masayuki; Sugawara, Toshiyuki; Yashiro, Tomoyasu; Saegusa, Kumiko; Furuno, Aki; Michikawa, Yuichi; Imai, Takashi

    2005-01-01

    Using cultured and nude mouse tumor cell (IA) derived frome a human lung cancer, we studied their radiosensitivity by focusing attention on the dynamics of tumor clonogens. The movement of clonogens in the regrowing IA tumor after X rays irradiation can be divided into three phases: first,: the early and rapid survival recovery (PLD repair) phase, second, the delay phase involving a certain lag in survival change, and third, the repopulation phase consisting of two stagea. Now we compare with the dynamics of tumor clonogens before or after exposure to X rays and carbon-ion beams. PLD repair was not observed in a carbon-ion beam. In relation to radiosensitivity and repair mechanism, we studied the gene expression of the cultured cell and nude tumor with a microarray method using 22K custom oligoallele. (author)

  5. Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

    International Nuclear Information System (INIS)

    Hanley, Joseph; Debois, Marc M.; Mah, Dennis; Mageras, Gikas S.; Raben, Adam; Rosenzweig, Kenneth; Mychalczak, Borys; Schwartz, Lawrence H.; Gloeggler, Paul J.; Lutz, Wendell; Ling, C. Clifton; Leibel, Steven A.; Fuks, Zvi; Kutcher, Gerald J.

    1999-01-01

    Purpose/Objective: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. Methods and Materials: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. Results: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free

  6. Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer.

    Science.gov (United States)

    Dinkel, J; Khalilzadeh, O; Hintze, C; Fabel, M; Puderbach, M; Eichinger, M; Schlemmer, H-P; Thorn, M; Heussel, C P; Thomas, M; Kauczor, H-U; Biederer, J

    2013-10-01

    Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. Manual measurements of the tumor longest diameter were significantly (p < 0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p < 0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement. By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Anesthesia condition for {sup 18}F-FDG imaging of lung metastasis tumors using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Cheon, Gi Jeong [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)], E-mail: larry@kcch.re.kr; Choi, Chang Woon; Lim, Sang Moo [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)

    2008-01-15

    Small animal positron emission tomography (PET) with {sup 18}F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal {sup 18}F-FDG PET. Methods: To determine the impact of anesthesia on {sup 18}F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of {sup 18}F-FDG in various tissues were evaluated. The {sup 18}F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of {sup 18}F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased {sup 18}F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest {sup 18}F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by {sup 18}F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal {sup 18}F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire {sup 18}F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

  8. Lung tumor tracking during stereotactic radiotherapy treatment with the CyberKnife: Marker placement and early results

    International Nuclear Information System (INIS)

    Nuyttens, J.J.; Prevost, J.B.; Praag, J.; Hoogeman, M.; Levendag, P.C.; Klaveren, R.J. van; Pattynama, P.M.T.

    2006-01-01

    Lung tumor tracking during stereotactic radiotherapy with the CyberKnife requires the insertion of markers in or close to the tumor. To reduce the risk of pneumothorax, three methods of marker placement were used: 1) intravascular coil placement, 2) percutaneous intrathoracal, and 3) percutaneous extrathoracal placement. We investigated the toxicity of marker placement and the tumor response of the lung tumor tracking treatment. Markers were placed in 20 patients with 22 tumors: 13 patients received a curative treatment, seven a palliative. The median Charlson Comorbidity Score was 4 (range: 1-8). Platinum fiducials and intravascular embolisation coils were used as markers. In total, 78 markers were placed: 34 intrathoracal, 23 intravascular and 21 extrathoracal. The PTV equaled the GTV + 5 mm. A median dose of 45 Gy (range: 30-60 Gy, in 3 fractions) was prescribed to the 70-85% isodose. The response was evaluated with a CTscan performed 6-8 weeks after the last treatment and routinely thereafter. The median follow-up was 4 months (range: 2-11). No severe toxicity due to the marker placement was seen. Pneumothorax was not seen. The local control was 100%. Four tumors in four patients showed a complete response, 15 tumors in 14 patients a partial response, and three tumors in two patients with metastatic disease had stable disease. No severe toxicity of marker placement was seen due to the appropriate choice of one of the three methods. CyberKnife tumor tracking with markers is feasible and resulted in excellent tumor response. Longer follow-up is needed to validate the local control

  9. Assessing Respiration-Induced Tumor Motion and Internal Target Volume Using Four-Dimensional Computed Tomography for Radiotherapy of Lung Cancer

    International Nuclear Information System (INIS)

    Liu, H. Helen; Balter, Peter; Tutt, Teresa; Choi, Bum; Zhang, Joy; Wang, Catherine; Chi, Melinda; Luo Dershan; Pan Tinsu; Hunjan, Sandeep; Starkschall, George; Rosen, Isaac; Prado, Karl; Liao Zhongxing; Chang, Joe; Komaki, Ritsuko; Cox, James D.; Mohan, Radhe; Dong Lei

    2007-01-01

    Purpose: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. Methods and Materials: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. Results: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. Conclusions: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung

  10. Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): Planning considerations and early toxicity

    International Nuclear Information System (INIS)

    Ong, Chin Loon; Palma, David; Verbakel, Wilko F.A.R.; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose: To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm 3 . Methods: Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc TM ) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy (V 5 , V 10 , V 15 and V 20 ) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP). Results: Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm 3 , respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V 5 (p 80 cm 3 , the contralateral lung V 5 best predicts RP. Limiting contralateral lung V 5 to <26% may reduce acute toxicity.

  11. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

    Science.gov (United States)

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2015-11-01

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress

  12. Tamaño del tumor y supervivencia en carcinoma de pulmón, estadio IA Tumor size and survival in lung cancer, stage IA

    Directory of Open Access Journals (Sweden)

    Gustavo Lyons

    2008-02-01

    Full Text Available El estadio determinado por el sistema TNM (tumor, ganglios, metástasis sigue siendo el factor predictor de supervivencia más importante en el carcinoma de pulmón. Sin embargo, varios estudios demostraron que el tamaño del tumor tenía valor pronóstico en sí mismo, aunque la relación entre tamaño tumoral y supervivencia dentro del grupo de tumores T1 todavía no es clara. El objetivo del presente estudio fue evaluar el valor del tamaño del tumor como factor pronóstico para la supervivencia en pacientes con carcinoma de pulmón de estadio IA, resecado quirúrgicamente. Se revisaron 79 pacientes con carcinoma de pulmón de células no pequeñas. En 34.4% de los pacientes (n = 28 el tamaño fue igual o menor a 1.5 cm. La mortalidad operatoria fue de 1.3%. Hubo recurrencia de la enfermedad en el 19%. Los pacientes con tumores de hasta 15 mm tuvieron una supervivencia a los 5 años de 95% (IC: 0.05 y con más de 15 mm, de 77%. (IC: 0.07, siendo la diferencia estadísticamente significativa (log-rank test: 0.035. La supervivencia libre de enfermedad fue de 95% en los tumores de hasta 15 mm y de 72% (IC: 0.09 en los de más de 15 mm. El análisis multivariado (Cox mostró que el mayor determinante del riesgo de mortalidad fue el tamaño mayor de 15 mm (riesgo relativo 25.9, IC: 2.3-292, p = 0.004. Este estudio demuestra la influencia del tamaño del tumor en estadio IA, lo cual puede tener importancia práctica en función de las recientes propuestas de investigación sistemática de pacientes con alto riesgo de cáncer pulmonar.TNM staging is an important long-term predictor for survival of lung cancer patients. Some studies have shown, however, that tumor size may have intrinsic prognostic value independent of TNM stage. The relationship between tumor size and survival is particularly unclear in T1 tumors. The objective of this study was to assess the prognostic value of tumor size in surgically resected stage I of non-small cell lung cancer

  13. Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy

    International Nuclear Information System (INIS)

    Tanio, Yoshiro; Watanabe, Masatoshi; Inoue, Tamotsu

    1990-01-01

    New cell lines of small cell lung cancer (SCLC) were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy. The advantage of this method was ease of obtaining specimens from lung tumors. Establishment of cell lines was successful with 4 of 13 specimens (30%). Clinical responses of the tumors showed considerable variation, but were well correlated with the in vitro sensitivity of the respective cell lines to chemotherapeutic drugs and irradiation. One of the cell lines was resistant to all drugs tested and irradiation, while another was sensitive to all of them. Although the acquired resistance of SCLC is the biggest problem in treatment, the natural resistance to therapy is another significant problem. Either acquired or natural, resistance mechanisms of SCLC may be elucidated by the use of such cell lines derived from untreated tumors. This method and these SCLC cell lines are expected to be useful for the serial study of biologic and genetic changes of untreated and pre-treated tumors, or primary and secondary tumors. (author)

  14. Modelo de tumor de pulmão em rato com o carcinossarcoma de Walker Lung tumor model in rats with Walker’s carcinosarcoma

    Directory of Open Access Journals (Sweden)

    Antero Gomes Neto

    2002-02-01

    Full Text Available OBJETIVO: Desenvolver um modelo de tumor pulmonar em ratos com o carcinossarcoma de Walker e verificar in vivo a presença de tumor por meio de tomografia computadorizada (TC. MÉTODOS: Ratos Wistar fêmeas (n=47 foram anestesiados com pentobarbital, intubados por traqueostomia e submetidos a toracotomia para injeção no parênquima pulmonar de células do tumor de Walker ou do veículo das mesmas. O estudo consistiu de duas etapas: na primeira desenvolveu-se a técnica de implante do tumor e estabeleceu-se o número de células necessário para um bom índice de pega tumoral. Na segunda etapa, determinou-se o volume do tumor em cm³ (Dxd²/2 através de TC e necropsia (6° dia do implante, e analizou-se a sobrevida dos animais. RESULTADOS: O índice de pega do tumor foi 93,3%, sendo 81,8% na primeira etapa e 100% na segunda. A mortalidade cirúrgica foi 17,0%. As medidas dos tumores foram semelhantes (0,099 vs. 0,111 cm³ na tomografia e na necropsia, respectivamente (r=0,993; pOBJECTIVE: To develop a lung tumor model in rats using Walker’s carcinosarcoma and to verify the presence in vivo of tumors using computerized tomography (CT. METHODS: Female Wistar rats (n=47 were anesthetized with pentobarbital, intubated through tracheostomy and submitted to thoracotomy; subsequently a 50-70 mu L volume containing Walker’s tumor cells, or the suspension of these same cells, was injected into the lung parenchyma. The study consisted of two phases: in the first a tumor implantation technique was developed and the number of cells required to attain a satisfactory tumor development rate was established. In the second phase, the tumor volume in cm³ (Dxd²/2 was determined through CT scan and necropsis, and the survival rates were analyzed. RESULTS: The overall tumor development rate was 93.3%, or rather, 81.1% in the first phase and 100% in the second. The surgical mortality rate was 17.0%. The average tumor volume was similar (0.099 vs. 0.111 cm

  15. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

    Directory of Open Access Journals (Sweden)

    Baohua Wang

    Full Text Available In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-α-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-α/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-α. After matching the TNF-α-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-α-mediated genes in normal and tumor lung tissues obtained from humans. Based on the TNF-α-mediated genes that were dysregulated in lung tumors, we developed a prognostic gene signature that effectively predicted recurrence-free survival in lung cancer in two validation cohorts. Resampling tests suggested that the prognostic power of the gene signature was not by chance, and multivariate analysis suggested that this gene signature was independent of the traditional clinical factors and enhanced the identification of lung cancer patients at greater risk for recurrence.

  16. Clinical Implementation of Intrafraction Cone Beam Computed Tomography Imaging During Lung Tumor Stereotactic Ablative Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruijiang; Han, Bin; Meng, Bowen [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Maxim, Peter G.; Xing, Lei; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2013-12-01

    Purpose: To develop and clinically evaluate a volumetric imaging technique for assessing intrafraction geometric and dosimetric accuracy of stereotactic ablative radiation therapy (SABR). Methods and Materials: Twenty patients received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At the beginning of each fraction, pretreatment cone beam computed tomography (CBCT) was used to align the soft-tissue tumor position with that in the planning CT. Concurrent with dose delivery, we acquired fluoroscopic radiograph projections during VMAT using the Varian on-board imaging system. Those kilovolt projections acquired during millivolt beam-on were automatically extracted, and intrafraction CBCT images were reconstructed using the filtered backprojection technique. We determined the time-averaged target shift during VMAT by calculating the center of mass of the tumor target in the intrafraction CBCT relative to the planning CT. To estimate the dosimetric impact of the target shift during treatment, we recalculated the dose to the GTV after shifting the entire patient anatomy according to the time-averaged target shift determined earlier. Results: The mean target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the 95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6, and 4.9 mm along the anterior-posterior, left-right, and superior-inferior directions. Thus, the time-averaged intrafraction gross tumor volume (GTV) position was always within the planning target volume. We observed some degree of target blurring in the intrafraction CBCT, indicating imperfect breath-hold reproducibility or residual motion of the GTV during treatment. By our estimated dose recalculation, the GTV was consistently covered by the prescription dose (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100% PD for 18 patients and >95% PD for all patients. Conclusions: Intrafraction CBCT during VMAT can provide

  17. Development of a Virtual Multidisciplinary Lung Cancer Tumor Board in a Community Setting

    Science.gov (United States)

    Stevenson, Marvaretta M.; Irwin, Tonia; Lowry, Terry; Ahmed, Maleka Z.; Walden, Thomas L.; Watson, Melanie; Sutton, Linda

    2013-01-01

    Purpose: Creating an effective platform for multidisciplinary tumor conferences can be challenging in the rural community setting. The Duke Cancer Network created an Internet-based platform for a multidisciplinary conference to enhance the care of patients with lung cancer. This conference incorporates providers from different physical locations within a rural community and affiliated providers from a university-based cancer center 2 hours away. An electronic Web conferencing tool connects providers aurally and visually. Methods: Conferences were set up using a commercially available Web conferencing platform. The video platform provides a secure Web site coupled with a secure teleconference platform to ensure patient confidentiality. Multiple disciplines are invited to participate, including radiology, radiation oncology, thoracic surgery, pathology, and medical oncology. Participants only need telephone access and Internet connection to participate. Results: Patient histories and physicals are presented, and the Web conferencing platform allows radiologic and histologic images to be reviewed. Treatment plans for patients are discussed, allowing providers to coordinate care among the different subspecialties. Patients who need referral to the affiliated university-based cancer center for specialized services are identified. Pertinent treatment guidelines and journal articles are reviewed. On average, there are 10 participants with one to two cases presented per session. Conclusion: The use of a Web conferencing platform allows subspecialty providers throughout the community and hours away to discuss lung cancer patient cases. This platform increases convenience for providers, eliminating travel to a central location. Coordination of care for patients requiring multidisciplinary care is facilitated, shortening evaluation time before definitive treatment plan. PMID:23942505

  18. Observation of Interfractional Variations in Lung Tumor Position Using Respiratory Gated and Ungated Megavoltage Cone-Beam Computed Tomography

    International Nuclear Information System (INIS)

    Chang, Jenghwa; Mageras, Gig S.; Yorke, Ellen; De Arruda, Fernando; Sillanpaa, Jussi; Rosenzweig, Kenneth E.; Hertanto, Agung; Pham, Hai; Seppi, Edward; Pevsner, Alex; Ling, C. Clifton; Amols, Howard

    2007-01-01

    Purpose: To evaluate the use of megavoltage cone-beam computed tomography (MV CBCT) to measure interfractional variation in lung tumor position. Methods and Materials: Eight non-small-cell lung cancer patients participated in the study, 4 with respiratory gating and 4 without. All patients underwent MV CBCT scanning at weekly intervals. Contoured planning CT and MV CBCT images were spatially registered based on vertebral anatomy, and displacements of the tumor centroid determined. Setup error was assessed by comparing weekly portal orthogonal radiographs with digitally reconstructed radiographs generated from planning CT images. Hypothesis testing was performed to test the statistical significance of the volume difference, centroid displacement, and setup uncertainty. Results: The vertebral bodies and soft tissue portions of tumor within lung were visible on the MV CBCT scans. Statistically significant systematic volume decrease over the course of treatment was observed for 1 patient. The average centroid displacement between simulation CT and MV CBCT scans were 2.5 mm, -2.0 mm, and -1.5 mm with standard deviations of 2.7 mm, 2.7 mm, and 2.6 mm in the right-left, anterior-posterior and superior-inferior directions. The mean setup errors were smaller than the centroid shifts, while the standard deviations were comparable. In most cases, the gross tumor volume (GTV) defined on the MV CBCT was located on average at least 5 mm inside a 10 mm expansion of the GTV defined on the planning CT scan. Conclusions: The MV CBCT technique can be used to image lung tumors and may prove valuable for image-guided radiotherapy. Our conclusions must be verified in view of the small patient number

  19. Measurement of Lung Cancer Tumor Markers in a Glass Wool Company Workers Exposed to Respirable Synthetic Vitreous Fiber and Dust

    Directory of Open Access Journals (Sweden)

    Shabnam Abtahi

    2018-01-01

    Full Text Available Background: Occupational exposures to respirable synthetic vitreous fiber (SVF and dust are associated with many lung diseases including lung cancer. Low-dose computed tomography is used for screening patients who are highly suspicious of having lung carcinoma. However, it seems not to be cost-effective. Serum biomarkers could be a useful tool for the surveillance of occupational exposure, by providing the possibility of diagnosing lung cancer in its early stages. Objective: To determine if serum carcinoembryonic antigen (CEA and cytokeratin fragment (CYFRA 21-1 levels in workers exposed more than normal population to respirable SVF and dust may be used as indicators of progression towards lung cancer. Methods: An analytic cross-sectional study, including 145 personnel of a glass wool company, along with 25 age-matched healthy individuals, was conducted to investigate the relationship between occupational exposure to respirable SVFs and dust and serum levels of two lung/pleura serum tumor markers, CEA and CYFRA 21-1, measured by ELISA. Results: Individuals exposed to higher than the recommended levels of respirable SVF had higher serum concentrations of CEA and CYFRA 21-1, compared to controls (p=0.008 and 0.040, respectively, as well as in comparison to those exposed to lower than recommended OSHA levels (p=0.046 and 0.033, respectively. Workers with >9 years work experience, had significantly (p=0.045 higher levels of serum CYFRA 21-1 than those with ≤9 years of experience. Conclusion: It seems that working for >9 years in sites with detectable levels of respirable SVF and dust would increase the levels of known lung cancer serum tumor markers. Transferring these workers to sites with respirable SVF concentrations lower than the limit of detection in the air is recommended.

  20. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Koto, Masashi; Imai, Reiko; Saegusa, Kimiko; Michikawa, Yuichi; Imai, Takashi

    2003-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IF127, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  1. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Baba, Masayuki; Sugawara, Toshiyuki; Furuno, Aki; Saegusa, Kimiko; Michikawa, Y.; Imai, Takashi

    2004-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IFI27, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  2. Biochemical Variations in Cytolytic Activity of Ortho- and Paramyxoviruses in Human Lung Tumor Cell Culture.

    Science.gov (United States)

    Zhirnov, O P

    2017-09-01

    Human lung cancer cells (Calu-3 line) were studied for the development of apoptosis, necrosis, and autophagy in response to infection with ortho- and paramyxoviruses. Biochemical pathways underlying various mechanisms of cell death differed for different viruses. When infected with murine Sendai paramyxovirus, Calu-3 cells demonstrated typical necrotic features such as cell swelling (but not shrinkage), lack of chromatin DNA laddering, of caspase 3 and 8 activation, and of apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) protein; an activation of antiapoptotic protein kinase Akt was also revealed. In contrast, infection with avian influenza virus A/FPV/Rostock/34 (H7N1 subtype) or Newcastle disease virus (NDV, avian paramyxovirus) caused the development of typical apoptotic markers such as cell shrinkage, ladder-type chromosomal DNA fragmentation, caspase 3 and 8 activation, and proteolytic cleavage of PARP in the absence of Akt activation. Notably, no upregulation of p53 protein phosphorylation was observed in all infected cells, which indicates that p53 is not involved in the virus-induced death of Calu-3 cells. Cell death caused by the influenza virus was accompanied by overstimulation of autophagy, whereas no stimulation of autophagy was observed in the NDV-infected cells. Infection with Sendai virus caused moderate stimulation of autophagy, which suggests that the mechanism of the virus-induced cell death and the balance between autophagy and cell death in infected cancer cells depend on the virus type and might significantly differ even for closely related viruses. Therefore, an optimal strategy for oncolytic virus-mediated destruction of tumor cells in cancer patients requires selection of the most appropriate oncolytic virus based on the mechanism of its cytolytic action in a particular type of tumor.

  3. Simultaneous Bilateral Spontaneous Pneumothorax Revealed Birt-Hogg-Dubè Syndrome

    Directory of Open Access Journals (Sweden)

    Alessandro Tamburrini

    2015-01-01

    Full Text Available Simultaneous bilateral spontaneous pneumothorax is a very rare clinical event, comprising approximately 1% of all spontaneous pneumothoraces. Clinical signs and symptoms may vary from mild chest pain and dyspnea to severe respiratory failure; nevertheless immediate treatment is mandatory as this condition can deteriorate and progress to tension pneumothorax. An underlying lung disease has been commonly described; in most istances primary or secondary tumors, interstitial diseases, and infectious diseases. Birt-Hogg-Dubè syndrome is a rare inherited disorder clinically characterized by multiple fibrofolliculomas, renal tumors, lung cysts, and, in ~24% of the patients, occurrence of spontaneous pneumothorax. In this case, we firstly report the concurrence of these rare conditions, as a patient presenting a simultaneous bilateral spontaneous pneumothorax was diagnosed with Birt-Hogg-Dubè syndrome based on the typical radiological findings and genetic testing of the folliculin gene located on chromosome 17.

  4. The variability of tumor motion and respiration pattern in Stereotactic Body RadioTherapy(SBRT) for Lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyun Joon; Bae, Sun Myeong; Baek, Geum Mun; Kang, Tae Young; Seo, Dong Rin [Dept. of Radiation Oncology, ASAN Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    The purpose of this study is to evaluate the variability of tumor motion and respiration pattern in lung cancer patients undergoing Stereotactic Body RadioTherapy(SBRT) by using On-Board imager (OBI) system and Real-time Position Management (RPM) System. This study population consisted of 60 lung cancer patient treated with stereotactic body radiotherapy (48 Gy / 4 fractions). Of these, 30 were treated with gating (group 1) and 30 without gating(group2): typically the patients whose tumors showed three-dimensional respiratory motion > 10 mm were selected for gating. 4-dimensional Computed Tomography (4DCT). Cone Beam CT (CBCT) and Fluoroscopy images were used to measure the tumor motion. RPM system was used to evaluate the variability of respiration pattern on SBRT for group1. The mean difference of tumor motion among 4DCT, CBCT and Fluoroscopy images in the cranio-caudal direction was 2.3 mm in group 1, 2. The maximum difference was 12.5 mm in the group 1 and 8.5 mm in group 2. The number of treatment fractions that patient's respiration pattern was within Upper-Lower threshold on SBRT in group 2 was 31 fractions. A patient who exhibited the most unstable pattern exceeded 108 times in a fraction. Although many patients in group 1 and 2 kept the reproducibility of tumor motion within 5 mm during their treatment, some patients exhibited variability of tumor motion in the CBCT and Fluoroscopy images. It was possible to improve the accuracy of dose delivery in SBRT without gating for lung cancer patient by using RPM system.

  5. Microwave Ablation of Lung Tumors Near the Heart: A Retrospective Review of Short-Term Procedural Safety in Ten Patients.

    Science.gov (United States)

    Maxwell, Aaron W P; Healey, Terrance T; Dupuy, Damian E

    2017-09-01

    To evaluate the rate of short-term complications associated with microwave ablation of lung tumors located near the heart. This HIPAA-compliant study was performed with a waiver for informed consent. Patients who underwent microwave ablation of lung tumors located 10 mm or less from the heart were identified by retrospective chart review. Both primary and metastatic tumors were included. Only tumors directly adjacent to one of the four cardiac chambers were included. All patients were treated in a single session using CT guidance with continuous electrocardiographic monitoring. Rates of new-onset arrhythmia and myocardial infarction (MI) within 90 days of the procedure were quantified, and evidence of cardiac or pericardiac injury was assessed for using post-ablation contrast-enhanced chest CT, electrocardiography (EKG), and-when available-echocardiography. Complications were graded using the Common Terminology Criteria for Adverse Events (CTCAE) system. Ten patients (four males, six females; mean age 73.1 ± 9.5 years) met all inclusion criteria. Mean tumor distance from the heart was 3 mm (range, 0-6 mm). New-onset arrhythmia was not observed during or following any of the microwave ablation treatments, and there were no documented 90-day MI events. CTCAE Grade 1 complications were observed by CT in eight patients, most commonly mild focal pericardial thickening. EKG and echocardiography were normal in all patients. No major complications (CTCAE Grade 3 or greater) were observed. Microwave ablation of lung tumors located 10 mm or less from the heart appears to have low associated short-term morbidity and may be appropriate in selected patients.

  6. Palliative treatment of primary lung tumors with Transpulmonary Chemoembolization (TPCE); Transpulmonale Chemoembolisation (TPCE) als palliatives Behandlungskonzept bei primaeren Lungentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Herzog, C.; Zangos, S.; Lindemayr, S. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie

    2007-03-15

    Purpose: To evaluate transpulmonary chemoembolization (TPCE) as a symptomatic palliative method for treating inoperable primary lung tumors. Materials and Method: From 2002 to 2005, 17 patients (17 males, 3 females; average age: 64.5 years) suffering from primary lung tumors were treated in 3.6 sessions (range: 2 to 8) using TPCE. The patients had the following primary tumors: adenocarcinoma (n = 6), pleural mesothelioma (n = 2), squamous cell carcinoma (n = 1), small cell carcinoma (n = 1), and non-small cell carcinoma (n = 7). After femoral vein puncture, tumor-supplying pulmonary arteries were selectively explored, and 5 - 10 mg mitomycin C and 5 - 10 mL lipiodol and microsphere particles (Spherex) (20 - 70 {mu}m in diameter) were applied with balloon protection. Diagnosis and follow-up were performed in 4-week intervals with unenhanced and contrast-enhanced computed tomography (CT). The mean follow-up was 11.3 months. Results: Treatment was well tolerated by all patients with no major side effects or complications. The laboratory parameters were not significantly influenced. 11.8 % of the patients (n = 2) showed high or moderate lipiodol uptake, and 76.5 % (n = 13) showed low lipiodol uptake. After evaluation of morphologic criteria, a mean volume regression of 12.1 ml (40.4 %) of the embolized areas was achieved in four patients (23.5 %), while a constant value was identified during follow-up for seven patients (41.2 %). In six patients (35.3 %), progression of the treated lung tumors was recorded. The tumor increased by a mean of 38.37 ml (165.38 %). (orig.)

  7. Portal imaging to assess set-up errors, tumor motion and tumor shrinkage during conformal radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Erridge, Sara C.; Seppenwoolde, Yvette; Muller, Sara H.; Herk, Marcel van; Jaeger, Katrien de; Belderbos, Jose S.A.; Boersma, Liesbeth J.; Lebesque, Joos V.

    2003-01-01

    Purpose: To investigate patient set-up, tumor movement and shrinkage during 3D conformal radiotherapy for non-small cell lung cancer. Materials and methods: In 97 patients, electronic portal images (EPIs) were acquired and corrected for set-up using an off-line correction protocol based on a shrinking action level. For 25 selected patients, the orthogonal EPIs (taken at random points in the breathing cycle) throughout the 6-7 week course of treatment were assessed to establish the tumor position in each image using both an overlay and a delineation technique. The range of movement in each direction was calculated. The position of the tumor in the digitally reconstructed radiograph (DRR) was compared to the average position of the lesion in the EPIs. In addition, tumor shrinkage was assessed. Results: The mean overall set-up errors after correction were 0, 0.6 and 0.2 mm in the x (left-right), y (cranial-caudal) and z (anterior-posterior) directions, respectively. After correction, the standard deviations (SDs) of systematic errors were 1.4, 1.5 and 1.3 mm and the SDs of random errors were 2.9, 3.1 and 2.0 mm in the x-, y- and z-directions, respectively. Without correction, 41% of patients had a set-up error of more than 5 mm vector length, but with the set-up correction protocol this percentage was reduced to 1%. The mean amplitude of tumor motion was 7.3 (SD 2.7), 12.5 (SD 7.3) and 9.4 mm (SD 5.2) in the x-, y- and z-directions, respectively. Tumor motion was greatest in the y-direction and in particular for lower lobe tumors. In 40% of the patients, the projected area of the tumor regressed by more than 20% during treatment in at least one projection. In 16 patients it was possible to define the position of the center of the tumor in the DRR. There was a mean difference of 6 mm vector length between the tumor position in the DRR and the average position in the portal images. Conclusions: The application of the correction protocol resulted in a significant

  8. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

  9. 64Cu-ATSM and 18FDG PET uptake and 64Cu-ATSM autoradiography in spontaneous canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Kristensen, Annemarie Thuri; Jørgensen, Jesper Tranekjær

    2012-01-01

    The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas.......The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas....

  10. Expression of Axl in Lung Adenocarcinoma and Correlation with Tumor Progression

    Directory of Open Access Journals (Sweden)

    Yi-Shing Shinh

    2005-12-01

    Full Text Available We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001 and the patient's clinical stage (P < .0001. Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer.

  11. Inhibition of Lung Tumor Colonization and Cell Migration with the Disintegrin Crotatroxin 2 Isolated from the Venom of Crotalus atrox

    Science.gov (United States)

    Galán, Jacob A.; Sánchez, Elda E.; Rodríguez-Acosta, Alexis; Soto, Julio G.; Bashir, Sajid; McLane, Mary Ann; Paquette-Straub, Carrie; Pérez, John C.

    2009-01-01

    Disintegrins are low molecular weight proteins (4-15 kDa) with an RGD binding region at their binding loop. Disintegrin and disintegrin-like proteins are found in the venom of four families of snakes: Atractaspididae, Elapidae, Viperidae and Colubridae. This report describes the biological activity of a disintegrin, crotatroxin 2, isolated by a three-step chromatography procedure from the venom of the Western diamondback rattlesnake (Crotalus atrox). The intact molecular mass for crotatroxin 2 was 7.384 kDa and 71 amino acids. Crotatroxin 2 inhibited human whole blood platelet aggregation with an IC50 of 17.5 nM, inhibited cell (66.3p) migration by 63%, and inhibited experimental lung tumor colonization in BALB/c mice at 1000 μg/kg. Our data suggest that while crotatroxin 2 inhibits platelet aggregation, cancer cell migration, and lung tumor colonization it is done via different integrins. PMID:18387648

  12. Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

    Science.gov (United States)

    Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie; Rasmussen, Torben Riis; Thygesen, Jesper; Hager, Henrik; Andersen, Niels Trolle; Rasmussen, Finn

    2017-05-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being studied, allowing for quick identification of the areas with the highest or lowest blood flow and blood volume. To examine whether DCE-CT could be used to distinguish between malignant and benign lung tumors in patients with suspected lung cancer. Fifty-nine patients with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. Using structured qualitative analysis of tumor blood flow patterns, it was possible to distinguish between malignant and benign lung tumors (Fisher-Freeman-Halton exact test, P  = 0.022). The inter-reader agreement of this method of analysis was slight to moderate (kappa = 0.30; 95% confidence interval [CI] = 0.13-0.46). DCE-CT in suspected lung cancer using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.

  13. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2016-12-01

    drug sen- sitivity in cancer cells. Nature 483(7391):570–575. 14. Adams JM, et al. (2005) Subversion of the Bcl-2 life/death switch in cancer de ...SCLC (N=15) other solid tumors (N=229) P= 0.001 Faber et al. Sup. Figure 3 # Cancer type 1 biliary tract 2 bladder 3 breast 4 cervix 5...lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis, Preclinical therapeutics 16. SECURITY

  14. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer

    Science.gov (United States)

    Ge, Xin; Jiang, Cheng-Fei; Shi, Zhu-Mei; Li, Dong-Mei; Liu, Wei-Tao; Yu, Xiaobo; Shu, Yong-Qian

    2016-01-01

    Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. In this study, we explored miR-137's role in the chemosensitivity of lung cancer. We found that the expression level of miR-137 is down-regulated in the human lung cancer tissues and the resistant cells strains: A549/paclitaxel(A549/PTX) and A549/cisplatin (A549/CDDP) when compared with lung cancer A549 cells. Moreover, we found that overe-expression of miR-137 inhibited cell proliferation, migration, cell survival and arrest the cell cycle in G1 phase in A549/PTX and A549/CDDP. Furthermore, Repression of miR-137 significantly promoted cell growth, migration, cell survival and cell cycle G1/S transition in A549 cells. We further demonstrated that the tumor suppressive role of miR-137 was mediated by negatively regulating Nuclear casein kinase and cyclin-dependent kinase substrate1(NUCKS1) protein expression. Importantly, miR-137 inhibits A549/PTX, A549/CDDP growth and angiogenesis in vivo. Our study is the first to identify the tumor suppressive role of over-expressed miR-137 in chemosensitivity. Identification of a novel miRNA-mediated pathway that regulates chemosensitivity in lung cancer will facilitate the development of novel therapeutic strategies in the future. PMID:26989074

  16. Recombinant protein rMBP-NAP restricts tumor progression by triggering antitumor immunity in mouse metastatic lung cancer.

    Science.gov (United States)

    Wang, Ting; Du, Mingxuan; Ji, Zhenyu; Ding, Cong; Wang, Chengbo; Men, Yingli; Liu, Shimeng; Liang, Taotao; Liu, Xin; Kang, Qiaozhen

    2018-02-01

    Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP), a potential TLR2 ligand, was reported to possess immunomodulatory effects on in situ tumors in our previous study. In the present work, we attempt to elucidate the effect of rMBP-NAP at the local immune modulation in B16-F10-induced metastatic lung cancer. Our results demonstrated that growth of B16-F10 melanoma metastases in the lung was significantly arrested after rMBP-NAP treatment, along with marked reduction in metastatic lung nodules and significant increase in survival. The treatment induced both local and systemic immune responses, which were associated with higher influx of CD4 + /CD8 + T cells and drove toward Th1-like and cytotoxic immune environment. Moreover, rMBP-NAP also showed significant anti-angiogenic activity by reducing vascularization in lung tumor sections. rMBP-NAP could induce antitumor immunity through activating Th1 cells and producing pro-inflammatory cytokines, which are responsible for the effective cytotoxic immune response against cancer progression. Our findings indicate that rMBP-NAP might be a novel antitumor therapeutic strategy.

  17. [Anti-tumor effect of the whole worm extract of Ascaris lumbricoides on Lewis lung carcinoma in mice].

    Science.gov (United States)

    Yang, Xiao-Jun; Yang, Jun-Ping; Huang, Yan-Qin; Liang, Hua; Yuan, Keng

    2013-12-01

    Forty-five C57BL/6 mice were randomly divided into five groups (A-E). Group B and D served as the control group of A and C. Each mouse of group A was intraperitoneally injected with 0.1 ml whole worm extract of Ascaris lumbricoides every other day, and 10 days later injected with 0.1 ml Lewis lung carcinoma (LLC) cells at right axillary subcutaneously region. Mice of group B were injected with normal saline and then developed tumor model. Each mouse of group C was injected with 0.1 ml LLC cells, and two days later, injected with 0.1 ml whole worm extract of A. lumbricoides every other day for 5 times. After the tumor model developed, mice in group D were injected with normal saline. Group E was the negative control group. Time intervals between implantation and active growth and tumor weight were recorded. Tumor inhibition rate was calculated. The average time interval between tumor implantation and measurable tumor growth for groups A, B, C and D was (7.0 +/-1.1), (6.0 +/- 0.7), (9.0 +/- 1.2) and (7.0 +/- 0.9) days. Tumor weight of [(338.9 +/- 282.2) mg] (P lumbricoides which may have an inhibitory effect on tumour growth.

  18. Pneumothorax, pleural effusion, and chest tube placement after radiofrequency ablation of lung tumors: incidence and risk factors.

    Science.gov (United States)

    Hiraki, Takao; Tajiri, Nobuhisa; Mimura, Hidefumi; Yasui, Kotaro; Gobara, Hideo; Mukai, Takashi; Hase, Soichiro; Fujiwara, Hiroyasu; Iguchi, Toshihiro; Sano, Yoshifumi; Shimizu, Nobuyoshi; Kanazawa, Susumu

    2006-10-01

    To retrospectively evaluate the incidence of and risk factors for pneumothorax, pleural effusion, and chest tube placement for pneumothorax after radiofrequency (RF) ablation of lung tumors. Institutional review board approval was obtained, with waiver of informed consent. This retrospective study comprised 224 ablation sessions for 392 tumors in 142 patients (92 men, 50 women; mean age, 64.0 years). Multiple variables were analyzed by using the Student t test or the Mann-Whitney U test for numerical values and by using the chi(2) test or the Fisher exact test for categorical values in order to assess risk factors for pneumothorax, pleural effusion, and chest tube placement for pneumothorax. The incidence of pneumothorax, pleural effusion, and chest tube placement for pneumothorax was 52% (117 of 224 sessions), 19% (42 of 224 sessions), and 21% (24 of 117 sessions), respectively. For pneumothorax, risk factors included male sex (P = .030), no history of pulmonary surgery (P pleural effusion, risk factors included the use of a cluster electrode (P = .008), decreased distance to the nearest pleura (P = .040), and decreased length of the aerated lung traversed by the electrode (P = .019). For chest tube placement for pneumothorax, risk factors included no history of pulmonary surgery (P = .002), the use of a cluster electrode (P pleural effusion can occur after RF ablation in patients with lung tumors, and chest tube placement for pneumothorax is sometimes required. (c) RSNA, 2006.

  19. TH-AB-202-01: Daily Lung Tumor Motion Characterization On EPIDs Using a Markerless Tiling Model

    International Nuclear Information System (INIS)

    Rozario, T; Chiu, T; Lu, W; Chen, M; Yan, Y; Bereg, S; Mao, W

    2016-01-01

    Purpose: Tracking lung tumor motion in real time allows for target dose escalation while simultaneously reducing dose to sensitive structures, thus increasing local control without increasing toxicity. We present a novel intra-fractional markerless lung tumor tracking algorithm using MV treatment beam images acquired during treatment delivery. Strong signals superimposed on the tumor significantly reduced the soft tissue resolution; while different imaging modalities involved introduce global imaging discrepancies. This reduced the comparison accuracies. A simple yet elegant Tiling algorithm is reported to overcome the aforementioned issues. Methods: MV treatment beam images were acquired continuously in beam’s eye view (BEV) by an electronic portal imaging device (EPID) during treatment and analyzed to obtain tumor positions on every frame. Every frame of the MV image was simulated by a composite of two components with separate digitally reconstructed radiographs (DRRs): all non-moving structures and the tumor. This Titling algorithm divides the global composite DRR and the corresponding MV projection into sub-images called tiles. Rigid registration is performed independently on tile-pairs in order to improve local soft tissue resolution. This enables the composite DRR to be transformed accurately to match the MV projection and attain a high correlation value through a pixel-based linear transformation. The highest cumulative correlation for all tile-pairs achieved over a user-defined search range indicates the 2-D coordinates of the tumor location on the MV projection. Results: This algorithm was successfully applied to cine-mode BEV images acquired during two SBRT plans delivered five times with different motion patterns to each of two phantoms. Approximately 15000 beam’s eye view images were analyzed and tumor locations were successfully identified on every projection with a maximum/average error of 1.8 mm / 1.0 mm. Conclusion: Despite the presence of

  20. SU-G-BRA-04: Simulation of Errors in Maximal Intensity Projection (MIP)-Based Lung Tumor Internal Target Volumes (ITV) Using Real-Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, D; Kishan, A; Santhanam, A; Min, Y; O’Connell, D; Lamb, J; Cao, M; Agazaryan, N; Yang, Y; Lee, P; Low, D [University of California, Los Angeles, Ca (United States)

    2016-06-15

    Purpose: To evaluate the effect of inter- and intra-fractional tumor motion on the error in four-dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real-time 2D-sagital cine-mode MRI acquired during lung SBRT treatments. Methods: Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP-based ITV+3–6mm margin). Sagittal slice cine-MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off-line optical-flow based deformable registration implemented on a GPU cluster. Pseudo-4DCT MIP-based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo-4DCT MIP-based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo-4DCT durations from 10-50s were analyzed. Results: Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo-4DCT based ITV volumes were observed that were as small as 29% of the entire treatment-ITV, depending on breathing irregularity and the duration of pseudo-4DCT. With an increase in duration of pseudo-4DCT from 10–50s the minimum volume acquired from 95% of all pseudo-4DCTs increased from 62%–81% of the treatment ITV. Conclusion: A 4DCT MIP-based ITV offers a ‘snap-shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap-shot varies according to inter- and intra-fractional tumor motion. Further work is required to investigate the dosimetric

  1. Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

    Science.gov (United States)

    Alifano, Marco; Mansuet-Lupo, Audrey; Lococo, Filippo; Roche, Nicolas; Bobbio, Antonio; Canny, Emelyne; Schussler, Olivier; Dermine, Hervé; Régnard, Jean-François; Burroni, Barbara; Goc, Jérémy; Biton, Jérôme; Ouakrim, Hanane; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline; Damotte, Diane

    2014-01-01

    Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC). Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all pnutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced. Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

  2. Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Demirci Ilhan

    2012-01-01

    Full Text Available Abstract Background Overdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, application of leuprolide and the Raf-1/MEK/ERK-1/2-pathway. Therefore, we examined GnrH receptor status in the examined specimen. Case presentation In 2010 a 77 year-old male patient was shown to have a tumor mass of about 1.7 cm diameter in the inferior lobe of the left lung. Since 2005, this tumor had hitherto been known and showed no progression in size. The patient suffered from prostate cancer 4 years ago and was treated with TUR-P, radiation therapy and the application of leuprolide. We conducted an explorative thoracotomy with atypical segment resection. The first histological diagnosis was a metastasis of prostate cancer with lymphangiosis carcinomatosa. After several immunohistochemical stainings, the diagnosis was changed to adenocarcinoma of the lung. We conducted a re-thoracotomy with lobectomy and systematic lymphadenectomy 12 days later. The tumor stage was pT1 N0 MX G2 L1 V0 R0. Further immunohistochemical studies were performed. We received the results 15 days after the last operation. The diagnosis was ultimately changed to typical carcinoid tumor without any signs of lymphatic vessel invasion. The patient recovered well from surgery, but still suffers from dyspnea and lack of physical performance. Lung function testing revealed no evidence of impairment. Conclusion The use of several immunohistochemical markers, careful evaluation of hematoxylin-eosin sections and the Ki-67 labelling index are important tools in discriminating between carcinoids

  3. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.

    Science.gov (United States)

    Vanderlaan, Paul A; Yamaguchi, Norihiro; Folch, Erik; Boucher, David H; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Goldstein, Michael A; Huberman, Mark S; Kocher, Olivier N; Costa, Daniel B

    2014-04-01

    Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special

  4. ERCC1 and Ki67 in Small Cell Lung Carcinoma and Other Neuroendocrine Tumors of the Lung Distribution and Impact on Survival

    DEFF Research Database (Denmark)

    Skov, Birgit Guldhammer; Holm, B.; Erreboe, A.

    2010-01-01

    .001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC + AC) and high grade NE (LCNEC + SCLC) (p ... with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic...... classification of NE tumors...

  5. Intrafractional Baseline Shift or Drift of Lung Tumor Motion During Gated Radiation Therapy With a Real-Time Tumor-Tracking System

    International Nuclear Information System (INIS)

    Takao, Seishin; Miyamoto, Naoki; Matsuura, Taeko; Onimaru, Rikiya; Katoh, Norio; Inoue, Tetsuya; Sutherland, Kenneth Lee; Suzuki, Ryusuke; Shirato, Hiroki; Shimizu, Shinichi

    2016-01-01

    Purpose: To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials: Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results: The average change in position of the treatment couch during the treatment time was 0.45 ± 2.23 mm (mean ± standard deviation), −1.65 ± 5.95 mm, and 1.50 ± 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions: Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers.

  6. Isolating and Testing Circulating Tumor DNA and Soluble Immune Markers During the Course of Treatment for Lung Cancer

    Science.gov (United States)

    2018-01-08

    Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

  7. Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.

    Science.gov (United States)

    Li, Kun; Xiu, Chen-Lin; Gao, Li-Ming; Liang, Hua-Gang; Xu, Shu-Feng; Shi, Ming; Li, Jian; Liu, Zhi-Wei

    2017-07-01

    Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.

  8. Gross tumor volume dependency on phase sorting methods of four-dimensional computed tomography images for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Yong; Lim, Sang Wook; Ma, Sun Young; Yu, Je Sang [Dept. of Radiation Oncology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of)

    2017-09-15

    To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.

  9. Clinical Significance of Tumor Marker Detection in Patients 
with Advanced Squamous Cell Carcimoma of the Lung

    Directory of Open Access Journals (Sweden)

    Ping LIANG

    2016-10-01

    Full Text Available Background and objective Due to it's concealment and no obvious symptoms, lung squamous carcimoma often has advanced disease when diagnosed. The aims of this study were to describe the characteristics of the disease, to evaluate the clinical importance of detection of multiple tumor markers in patients with squamous cell carcinoma of the lung. Methods The characteristics of all patients with advanced squamous cell lung cancer treated in Beijing Cancer Hospital of Chinese Academy of Medical Sciences during Jan. 2011 to Dec. 2015 were identified by cases reviewing and data extracting. The characteristics, detection levels and sensitivity of multiple tumor makers among patients were described. Results The 260 patients were treated with mean age of (59.4±9.2 years, 85.8% (n=223 of them were male, 14.2% (n=37 of them were female. 78.1% (n=203 of all were smokers and 3.1% (n=8 of patients had family history of tumor. The positive rate of cytokerantin 19 fragment (CYFRA21-1 was 71.2%, which was the highest among five tumor markers. The five tumor markers median level had no statistical significance between different tumor (T stages and node (N stages (all P>0.05, only the positive rate of SCC had statistical significance between different T stages (P=0.035. The combination measurement of CYFRA21-1+carcinogen-embryonic antigen (CEA, CYFRA21-1+CEA+cancer antigen (CA125, CA125+CYFRA21-1+CEA+neuron specific enolase (NSE, and CA125+CYFRA21-1+NSE+CEA+squamous cell carcinoma antigen (SCC were better and had higher clinical values, the positive rates were 82.7%, 84.6%, 85.0% and 86.2%, respectively. Conclusion The positive rate of CYFRA21-1 was the highest and the sensitivity of single test of five tumor markers was low, the combination of multiple tumor markers increased the sensitivity of diagnosis of SQCLC, the combination of CA125, CYFRA21-1 and CEA was the best choice.

  10. Histopathologic Consideration of Fiducial Gold Markers Inserted for Real-Time Tumor-Tracking Radiotherapy Against Lung Cancer

    International Nuclear Information System (INIS)

    Imura, Mikado; Yamazaki, Koichi; Kubota, Kanako C.; Itoh, Tomoo; Onimaru, Rikiya; Cho, Yasushi; Hida, Yasuhiro; Kaga, Kichizo; Onodera, Yuya; Ogura, Shigeaki; Dosaka-Akita, Hirotoshi; Shirato, Hiroki; Nishimura, Masaharu

    2008-01-01

    Purpose: Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Methods and Materials: Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Results: Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Conclusions: Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion

  11. An Evaluation of Two Internal Surrogates for Determining the Three-Dimensional Position of Peripheral Lung Tumors

    International Nuclear Information System (INIS)

    Spoelstra, Femke; Soernsen de Koste, John R. van; Vincent, Andrew; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh

    2009-01-01

    Purpose: Both carina and diaphragm positions have been used as surrogates during respiratory-gated radiotherapy. We studied the correlation of both surrogates with three-dimensional (3D) tumor position. Methods and Materials: A total of 59 repeat artifact-free four-dimensional (4D) computed tomography (CT) scans, acquired during uncoached breathing, were identified in 23 patients with Stage I lung cancer. Repeat scans were co-registered to the initial 4D CT scan, and tumor, carina, and ipsilateral diaphragm were manually contoured in all phases of each 4D CT data set. Correlation between positions of carina and diaphragm with 3D tumor position was studied by use of log-likelihood ratio statistics. Models to predict 3D tumor position from internal surrogates at end inspiration (EI) and end expiration (EE) were developed, and model accuracy was tested by calculating SDs of differences between predicted and actual tumor positions. Results: Motion of both the carina and diaphragm significantly correlated with tumor motion, but log-likelihood ratios indicated that the carina was more predictive for tumor position. When craniocaudal tumor position was predicted by use of craniocaudal carina positions, the SDs of the differences between the predicted and observed positions were 2.2 mm and 2.4 mm at EI and EE, respectively. The corresponding SDs derived with the diaphragm positions were 3.7 mm and 3.9 mm at EI and EE, respectively. Prediction errors in the other directions were comparable. Prediction accuracy was similar at EI and EE. Conclusions: The carina is a better surrogate of 3D tumor position than diaphragm position. Because residual prediction errors were observed in this analysis, additional studies will be performed using audio-coached scans.

  12. Residual motion of lung tumors in end-of-inhale respiratory gated radiotherapy based on external surrogates

    International Nuclear Information System (INIS)

    Berbeco, Ross I.; Nishioka, Seiko; Shirato, Hiroki; Jiang, Steve B.

    2006-01-01

    It has been noted that some lung tumors exhibit large periodic motion due to respiration. To limit the amount of dose to healthy lung tissues, many clinics have begun gating radiotherapy treatment using externally placed surrogates. It has been observed by several institutions that the end-of-exhale (EOE) tumor position is more reproducible than other phases of the breathing cycle, so the gating window is often set there. From a treatment planning perspective, end-of-inhale (EOI) phase might be preferred for gating because the expanded lungs will further decrease the healthy tissue within the treatment field. We simulate gated treatment at the EOI phase, using a set of recently measured internal/external anatomy patient data. This paper attempts to answer three questions: (1) How much is the tumor residual motion when we use an external surrogate gating window at EOI? (2) How could we reduce the residual motion in the EOI gating window? (3) Is there a preference for amplitude- versus phase-based gating at EOI? We found that under free breathing conditions the residual motion of the tumors is much larger for EOI phase than for EOE phase. The mean values of residual motion at EOI were found to be 2.2 and 2.7 mm for amplitude- and phase-based gating, respectively, and, at EOE, 1.0 and 1.2 mm for amplitude- and phase-based gating, respectively. However, we note that the residual motion in the EOI gating window is correlated well with the reproducibility of the external surface position in the EOI phase. Using the results of a published breath-coaching study, we deduce that the residual motion of a lung tumor at EOI would approach that at EOE, with the same duty cycle (30%), under breath-coaching conditions. Additionally, we found that under these same conditions, phase-based gating approaches the same residual motion as amplitude-based gating, going from a 28% difference to 11%, for the patient with the largest difference between the two gating modalities. We conclude

  13. Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits.

    Science.gov (United States)

    Hamamoto, Shinichi; Okuma, Tomohisa; Yamamoto, Akira; Kageyama, Ken; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

    2013-05-01

    To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P OK-432 may lead to indirectly activation of systemic antitumor immunity. © RSNA, 2013.

  14. Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA.

    Science.gov (United States)

    Johnson, Alison C; Dô, Pascal; Richard, Nicolas; Dubos, Catherine; Michels, Jean Jacques; Bonneau, Jessica; Gervai