Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells

International Nuclear Information System (INIS)

Chamoto, Kenji; Wakita, Daiko; Takeshima, Tsuguhide

2009-01-01

Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG+OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG+OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG+OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG+OVA-liposome allowed the augmented induction of OVA-tetramer + LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (author)

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

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

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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.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

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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.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

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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.

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

Portal Vein Tumor Thrombus of Liver Metastasis from Lung Cancer

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Ryoko Ogawa

2009-01-01

Full Text Available We report a case of liver metastasis of lung carcinoma with portal vein tumor thrombus (PVTT. Although the primary lesion of lung tumor remained unchanged, the patient rapidly developed wide-spread metastases and formed PVTT of liver metastasis. The primary lesion showed features of mixed Clara and bronchial surface epithelial cell component type adenocarcinoma with small foci of micropapillary pattern. Micropapillary pattern was observed in the metastatic lesions in the liver and PVTT. Micropapillary pattern lung adenocarcinoma may develop rapid metastases and cause PVTT associated with liver metastasis. We should perform a detailed examination to establish correct diagnosis.

Squamous cell lung carcinoma presenting as melena: a case report and review of the literature

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Ibrahim Azar

2017-10-01

Full Text Available Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.

Classification of primary lung tumors in dogs: 210 cases (1975-1985)

International Nuclear Information System (INIS)

Ogilvie, G.K.; Haschek, W.M.; Withrow, S.J.; Richardson, R.C.; Harvey, H.J.; Henderson, R.A.; Fowler, J.D.; Norris, A.M.; Tomlinson, J.; McCaw, D.

1989-01-01

Two hundred ten dogs that had primary lung tumors diagnosed between 1975 and 1985 were evaluated. The majority of the tumors were classified as adenocarcinoma (74.8%) and alveolar carcinoma (20%). The most common clinical signs of disease were cough (52%), dyspnea (23.8%), lethargy (18.1%), weight loss (12.4%), and tachypnea (4.8%). The clinical methods that were most successful in directly or indirectly leading to a diagnosis of primary lung tumor were thoracic radiography (77.1%) and cytologic examination of fine-needle aspirate specimens (24.8%)

[A case of lung abscess during chemotherapy for testicular tumor].

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Hayashi, Yujiro; Miyago, Naoki; Takeda, Ken; Yamaguchi, Yuichiro; Nakayama, Masashi; Arai, Yasuyuki; Kakimoto, Ken-ichi; Nishimura, Kazuo

2014-05-01

32-year-old man was seen in a clinic because of prolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor. The lung abscess was treated successfully with antibiotics.

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

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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

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

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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.

Effect of induced hyperglycemia on metastatic spreading in Lewis lung carcinoma

International Nuclear Information System (INIS)

Shmakova, N.L.; Fomenkova, T.E.; Fadeeva, T.A.

1991-01-01

The effect of induced hyperglycemia on the intensity of metastatic dissemination of Lewis lung carcinoma was investigated in experiments on mice. Neither long-, nor short-term hyperglycemia, induced at different phases of dissemination, influenced the intensity of metastatic spreading, primary tumor growth, the time of appearance of metastases, and the average life duration of tumor-bearing animals

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

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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.

Anti-CEA monoclonal antibody in the diagnosis of colorectal, lung and ovarian carcinoma

International Nuclear Information System (INIS)

Jiang, N.; Lu, B.; Lu, X.; Sha, X.; Yue, D.

2000-01-01

This study evaluated the diagnostic value of radioimmnoimaging (RII) with 99 Tc labeled monoclonal antibody C50, raised originally against carcinoembryonic antigen (anti-CEA) in various tumors. 152 pathologically confirmed patients with a tumor were imaged prior to surgery with an anti-CEA monoclonal antibody labeled with 99 Tc. There were 115 patients with ovarian carcinoma, 26 patients with colorectal carcinoma and 11 patients with lung carcinoma. Images were acquired at 3-6 h post injection and were analyzed by the double blind method. Images of patients with ovarian cancer were compared with B-ultrasound images. Immunohistochemical staining was performed on all cases of colorectal cancer. All RII images demonstrated excellent contrast, clear lesions, and no serious toxic or other side reactions occurred. Transient chills and fever were observed in 3 cases. This study showed a sensitivity=88.2%, specificity=83.2%, and an accuracy=4.0%. The smallest lesion size detected was 2 x 2 cm. The total combined lesion detection rate for primary, metastatic, and recurrence lesions was 84.4%. We conclude that 99 Tc labeled anti-CEA MoAb C50 can be used in the diagnosis of colorectal carcinoma, ovarian carcinoma, and lung carcinoma

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

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

Primary epithelial myoepithelial carcinoma of lung, reporting of a rare entity, its molecular histogenesis and review of the literature.

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Arif, Farzana; Wu, Susan; Andaz, Shahriyour; Fox, Stewart

2012-01-01

Primary epithelial myoepithelial carcinoma of lung is a rare entity and is thought to arise from the submucosal bronchial glands distributed throughout the lower respiratory tract. Because of the rarity of this tumor, we describe one case of epithelial myoepithelial carcinoma arising in the bronchus intermedius and presenting as an endobronchial mass. A 57-year-old male patient presented with an incidental finding of an endobronchial mass located in the lumen of the right lower lobe bronchus and caused near total luminal occlusion of the bronchus. An endobronchial carcinoid tumor was entertained clinically. Subsequently the patient underwent an uneventful videothoracoscopic lobectomy of lower and middle lobes of the right lung. Morphologically and immunohistochemically the tumor was characterized by two cell populations with epithelial and myoepithelial cells forming duct-like structure. The final diagnosis of epithelial myoepithelial carcinoma of lung was rendered.

Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis

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Giulia Fregni

2018-03-01

Full Text Available Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis. We also demonstrate that tumor-associated MSCs induce the expression of genes associated with an aggressive phenotype in primary lung cancer cells and selectively promote their dissemination rather than local growth. Our observations provide insight into mechanisms by which the stroma promotes lung cancer metastasis. Keywords: Tumor-associated MSCs, lung cancer, metastasis, GREM1, LOXL2, ADAMTS12, ITGA11

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

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In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to

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.

Mucoepidermoid carcinoma of the conjunctiva with lung metastasis

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Pukhraj Rishi

2015-01-01

Full Text Available A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC, indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis.

Subclassification of pulmonary non-small cell lung carcinoma in fine needle aspirates using a limited immunohistochemistry panel

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Kusum Kapila

2013-01-01

Conclusion: Use of limited IHC panel helps categorize primary versus secondary tumors to the lung. The p63 is a useful marker for detecting squamous cell carcinoma. In countries where antibodies are not readily available, using a limited IHC panel of TTF-1, p63, and CK7 can help further type NSCLC lung tumors.

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)

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

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.

Potential targets for lung squamous cell carcinoma

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Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

Immunohistochemical detection of epidermal growth factor receptor in radiation-induced lung tumors in Beagle dogs

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Gillett, N A; Haley, P J; Hahn, F F

1988-12-01

Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to {sup 239}PuO{sub 2}- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

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Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I.; Creighton, Chad J.; Kheradmand, Farrah; DeMayo, Francesco J.

2015-01-01

Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 resul...

Detection and Analysis of EGFR and KRAS Mutations 
in the Patients with Lung Squamous Cell Carcinomas

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Hui ZHANG

2015-10-01

Full Text Available Background and objective Activating mutations in epidermal growth factor receptor (EGFR and KRAS are important markers in non-small cell lung cancer. However, EGFR and KRAS gene mutations in lung squamous cell carcinoma are rarely reported. The aim of this study was to analyze EGFR and KRAS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for naïve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KRAS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%, KRAS mutations were detected in 7 cases (5%, and the presence of both EGFR and KRAS mutations was detected in 1 case (0.7%. EGFR mutations occurred more often in females than in males (33.3% vs 16.5% and in patients that never smoked than in those who smoke (29.6% vs 16.1%. However, the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, and different biopsy type. KRAS mutations occurred more often in males than in females (5.5% vs 0%, but the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05. Conclusion EGFR and KRAS mutations were low in lung squamous cell carcinomas, and had no significant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KRAS mutations should be detected in patients with lung squamous cell carcinomas.

Therapeutic Non-Toxic Doses of TNF Induce Significant Regression in TNFR2-p75 Knockdown Lewis Lung Carcinoma Tumor Implants

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Sasi, Sharath P.; Bae, Sanggyu; Song, Jin; Perepletchikov, Aleksandr; Schneider, Douglas; Carrozza, Joseph; Yan, Xinhua; Kishore, Raj; Enderling, Heiko; Goukassian, David A.

2014-01-01

Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (ptumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics. PMID:24664144

Radiographic findings of oat cell carcinoma of the lung

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Park, Y. H.; Yoon, Y.; Kim, S. Y.

1984-01-01

Growth of oat cell carcinoma tends to be invasive and extends rapidly through the bronchial lymphatics to the hilus and mediastinum, where bulky mass of tumor develop. Authors have analysed roentgenologic manifestations of 22 cases of histologically proven oat cell carcinoma of the lung seen during the period of 3 years from Jan, 1980 to May. 1983. The results 18 males and 4 females. Incidence was the most common in 7th decade as 45%. 2. Chief complaints are cough, sputum and dyspnea. Metastatic symptoms are hoarseness, SVC syndrome and back pain. 3. The radiographic findings of oat cell carcinoma were as follows. 1) hilar and perihilar mass 73% 2) Mediastinal mass 64% 3) Bronchial obstruction sign 55% 4) Peripheral mass 18% 5) Pleural effusion 18%

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

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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

CT-guided percutaneous conformal cryoablation for lung carcinoma

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Yueyong, Xiao; Bin, Wu; Xiao, Zhang; Hongjun, Li; Da, Yu; Jie, Li; Jun, Li [Department of Radiology, PLA General Hospital, Beijing (China)

2010-02-15

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

CT-guided percutaneous conformal cryoablation for lung carcinoma

International Nuclear Information System (INIS)

Xiao Yueyong; Wu Bin; Zhang Xiao; Li Hongjun; Yu Da; Li Jie; Li Jun

2010-01-01

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

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Chen, Ming-Feng; Yang, Chih-Min; Su, Cheng-Ming; Liao, Jiunn-Wang; Hu, Miao-Lin

2011-01-01

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

The Notch ligand delta-like 3 promotes tumor growth and inhibits Notch signaling in lung cancer cells in mice

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Deng, San-Ming; Yan, Xian-Chun; Liang, Liang; Wang, Li; Liu, Yuan; Duan, Juan-Li; Yang, Zi-Yan; Chang, Tian-Fang; Ruan, Bai; Zheng, Qi-Jun; Han, Hua

2017-01-01

Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues. Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro, and enhanced tumor growth when inoculated in vivo in mice. The Dll3-mediated proliferation could be due to increased Akt phosphorylation in LLC cells, because an Akt inhibitor counteracted Dll3-induced proliferation. Moreover, Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling. - Highlights: • The level of Dll3 in Lewis lung carcinoma changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with TNF-α. • The Dll3 was rarely detectable in the para-carcinoma tissues, but positive in 82.1% of NSCLC tissues from 84 patients. • Overexpression of Dll3 in LLC cells promoted tumor growth but did not remarkably alter TME after inoculated in mice. • Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro in an Akt-dependent way. • Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling.

Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

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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)

Immunocytochemical characterization of lung tumors in fine-needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma.

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Bruderman, I; Cohen, R; Leitner, O; Ronah, R; Guber, A; Griffel, B; Geiger, B

1990-10-15

In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine-needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma.

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

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Kodama, Tetsuro

1978-01-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

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Kodama, T [Hiroshima Univ. (Japan). School of Medicine

1978-08-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining.

[Indication for limited surgery on small lung cancer tumors measuring 1cm or less in diameter on preoperative computed tomography and long-term results].

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Togashi, K; Koike, T; Emura, I; Usuda, H

2008-07-01

Non-invasive lung cancers showed a good prognosis after limited surgery. But it is still uncertain about invasive lung cancers. We investigated the indications for limited surgery for small lung cancer tumors measuring 1 cm or less in diameter on preoperative computed tomography (CT). This study retrospectively analyzed of 1,245 patients who underwent complete resection of lung cancer between 1989 and 2004 in our hospital. Sixty-two patients (5%) had tumors measuring 1 cm or less in diameter. The probability of survival was calculated using the Kaplan-Meier method. All diseases were detected by medical checkup, 52 % of the patients were not definitively diagnosed with lung cancer before surgery. Adenocarcinoma was histologically diagnosed in 49 patients (79%). Other histologic types included squamous cell carcinoma (8), large cell carcinoma (1), small cell carcinoma (1), carcinoid (2), and adenosquamous cell carcinoma (1). Fifty-seven patients (92%) showed pathologic stage IA. The other stages were IB (2), IIA (1), and IIIB (2). There were 14 bronchioloalveolar carcinomas (25% of IA diseases). The 5-year survival rates of IA patients were 90%. The 5-year survival rate of patients with tumors measuring 1cm or less diameter was 91% after lobectomy or pneumonectomy, and 90% after wedge resection or segmentectomy. There were 3 deaths from cancer recurrence, while there were no deaths in 14 patients with bronchioloalveolar carcinoma After limited surgery, non-invasive cancer showed good long-term results, while invasive cancer showed a recurrence rate of 2.3% to 79% even though the tumor measured 1 cm or less in diameter on preoperative CT.

Mucoepidermoid carcinoma of the lung with initial presentation of microangiopathic hemolytic anemia and thrombocytopenia

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Yuan-Chun Huang

2017-12-01

Full Text Available Mucoepidermoid carcinoma is a rare entity of lung malignancy that is subclassified into high-grade or low-grade types according to its histological features. High-grade mucoepidermoid carcinoma is a more aggressive form of malignancy, with a tendency towards lymph node involvement and distant metastasis. Cancer-related microangiopathic hemolytic anemia as a less common situation of paraneoplastic syndrome may be encountered with metastatic malignancy, but has not been reported previously in mucoepidermoid carcinoma of the lung. Herein, we report a 78-year-old male patient who presented with hemoptysis for one day. Laboratory tests showed microangiopathic hemolytic anemia and thrombocytopenia. A chest X-ray demonstrated consolidation in the left lung field. Chest computed tomography revealed a mass in the left upper lobe, and a subsequent bronchoscopic biopsy was performed. The histopathological results indicated a high-grade mucoepidermoid carcinoma. Magnetic resonance imaging of the brain demonstrated leptomeningeal carcinomatosis. The patient refused systemic chemotherapy, and palliative radiation therapy only was conducted for local disease control. The patient has performed well for 12 months to date since diagnosis of the tumor.

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)

A case of limbic encephalitis with small cell lung carcinoma in which the cognitive function improved and redeteriorated during tumor therapy

International Nuclear Information System (INIS)

Fujimoto, So; Yamaguchi, Yasuhiro; Gotanda, Hiroshi

2010-01-01

We report the findings regarding a 70-year-old man with paraneoplastic limbic encephalitis. He presented with a chief complaint of inability to recall any events. He had been well until one month before admission, and then he abruptly began to show progressive amnesia. At admission, the patient's score on the Revised Hasegawa Dementia Scale (HDS-R) showed a decline to 13/30, thus indicating the existence of severe disorientation and an impaired memory. The brain CT and electroencephalogram (EEG) showed no specific abnormalities and an analysis of cerebrospinal fluid showed only a mild increase in the total protein level. A chest X-ray film revealed a mass in the right hilum, while a histological analysis of the biopsied specimen finally established a diagnosis of small cell lung carcinoma. The fluorodeoxyglucose (FDG)-positron emission tomography (PET) and the enhanced brain MRI showed a single small metastatic lesion in the cerebellum. After the 1st course of chemotherapy and whole brain radiation, cognitive function, especially the short-term memory, remarkably improved and the HDS-R score increased to 21/30. However, the tumor again increased in size during the 3rd and 4th courses of chemotherapy. Interestingly, cognitive function also worsened again and the score of HDS-R declined to 15/30, 20 weeks after the start of chemotherapy. Limbic encephalitis can be associated with malignant tumors, such as small cell lung carcinoma, and some reported cases have shown a cognitive improvement after tumor therapy. In our case, we also observed a reworsening of the cognitive function in association with the acquired chemoresistence. (author)

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

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Jian Liu

2015-03-01

Full Text Available Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

Radiofrequency Ablation of Lung Tumors

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... News Physician Resources Professions Site Index A-Z Radiofrequency Ablation (RFA) / Microwave Ablation (MWA) of Lung Tumors ... and Microwave Ablation of Lung Tumors? What are Radiofrequency and Microwave Ablation of Lung Tumors? Radiofrequency ablation, ...

Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report

International Nuclear Information System (INIS)

Chen, Xiao-Hong; Bao, Yang-Yang; Zhou, Shui-Hong; Wang, Qin-Ying; Zhao, Kui

2013-01-01

Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for only 0.8% of all tonsillar tumors, with only 100 cases reported in the English-language literature. Various malignant lung carcinomas may metastasize to the tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma have been reported. A 67-year-old female underwent a right tonsillectomy because of a sore throat and an enlarged right tonsil. The postoperative pathology showed right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated metabolic activity in the lower lobe of the right lung. In addition, hypermetabolic foci were noted in the lymph nodes of the right neck and mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient received chemotherapy and died of multiple distant metastases after 6 months. This is the first report using PET/CT to evaluate tonsillar metastasis from lung SCNC

Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

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Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

2017-09-01

The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

International Nuclear Information System (INIS)

Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

2009-01-01

The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

Alterations of tumor suppressor genes (Rb, p16, p27 and p53) and an increased FDG uptake in lung cancer

International Nuclear Information System (INIS)

Sasaki, Masayuki; Sugio, Kenji; Kuwabara, Yasuo

2003-01-01

The FDG uptake in lung cancer is considered to reflect the degree of malignancy, while alterations of some tumor suppressor genes are considered to be related to the malignant biological behavior of tumors. The aim of this study is to examine the relationship between FDG-PET and alterations in the tumor suppression genes of lung cancer. We examined 28 patients with primary lung cancer who underwent FDG-PET before surgery consisting of 17 patients with adenocarcinoma, 10 with squamous cell carcinoma and 1 with large cell carcinoma. The FDG-PET findings were evaluated based on the standardized uptake value (SUV). Alterations in the tumor suppressor genes, Rb, p16, p27 and p53, were evaluated immunohistochemically. The FDG uptake in lung cancer with alteration in each tumor suppressor gene tended to be higher than in those genes without alterations, although the differences were not significant. In 15 tumors with alterations in either tumor suppressor genes, the FDG uptake was 6.83±3.21. On the other hand, the mean FDG uptake was 1.95 in 2 tumors without alterations in any genes. The difference in the FDG uptake between the 2 groups was statistically significant (p<0.001). In conclusion, the presence of abnormalities in the tumor suppressor genes, which results in an accelerated cell proliferation, is thus considered to increase the FDG uptake in lung cancer. (author)

Time-dependent cell disintegration kinetics in lung tumors after irradiation

International Nuclear Information System (INIS)

Chvetsov, Alexei V; Palta, Jatinder J; Nagata, Yasushi

2008-01-01

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T 1/2 . The half-life T 1/2 is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T 1/2 of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations

Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

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Phadke, Manali; Krynetskaia, Natalia [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Mishra, Anurag [Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Krynetskiy, Evgeny, E-mail: ekrynets@temple.edu [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States)

2011-07-29

Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

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Polo, Valentina; Pasello, Giulia; Frega, Stefano; Favaretto, Adolfo; Koussis, Haralabos; Conte, Pierfranco; Bonanno, Laura

2016-01-01

Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization. PMID:26933818

A non-metastatic remote effect of lung carcinoma.

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van der Pol, B A; Planten, J T

1987-01-01

A 37-year-old man, who had an oat cell carcinoma of the left lung, lost in a few months a substantial part of both visual fields, on account of a destructive retinal process. This syndrome is known in the literature as a visual paraneoplastic syndrome, which clinically shows the very rapid development of a pseudoretinitis pigmentosa sine pigmento. For most of the patients described the visual problem was the presenting symptom. In contrast with most other described cases, our patient responded very well to systemic tumor treatment and his ocular process also came to a standstill after some delay. The nature of the relationship between the primary tumor and the photoreceptor destruction is not yet clear in detail. An auto-immune process probably forms the basis of the syndrome, but hormonal activity of the tumor could not be excluded in all cases.

The effect of dose protraction on the incidence of lung carcinomas in beagle dogs with internally deposited β-emitting radionuclides

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Griffith, W.C.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Snipes, M.B.

1992-01-01

Studies using Beagle dogs were conducted to understand health effects when lung is the primary organ irradiated after inhaling insoluble radioactive particles containing one of four β-emitting radionuclides, 90 Y, 91 Y, 144 Ce, or 90 Sr. The low-LET β irradiation was delivered over a wide range of total doses and dose rate patterns that protracted the dose to lung from about 1 wk to several years. The tumor incidence rates for lung carcinomas were estimated using a proportional hazard rate model. These studies suggest that dose protraction only affects production of lung carcinomas at doses above 50 Gy

Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

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Dilip K Das

2011-01-01

Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

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2018-05-14

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.

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Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I; Creighton, Chad J; Kheradmand, Farrah; DeMayo, Francesco J

2015-03-03

Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Not traditional regimes of radiotherapeutic dose fractionation as modifier of radiotherapy for carcinoma of lungs

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Artemova, N.A.

2008-01-01

The efficiency of applying various of radiotherapeutic dose fractionation was analyzed. The results of the own studies performed at the Scientific and Research Institute of Oncology and Medical Radiology for elaborating not traditional regimes of radiotherapeutic dose fractionation (a dynamic fractionation applying enlarged regimes at the first stage and the classic ones at the second stage) were presented. Appliance of the modified radiotherapy for the epidermoid carcinoma of the lungs allowed to increase the objective response from 45,3+-3% to 80+-5% the tumor disappearing completely in 40+-6% of patients as compared with 10+-2%. Appliance of the intensive not traditional variant of the radiotherapy dynamic fractionation in case of a small cell carcinoma of the lungs resulted in the therapy duration reduction from 6 to 4 weeks. Thus the not traditional dose fractionation might become a mechanism for the improving the radiotherapy of persons suffering from the carcinoma of the lungs. (authors)

Correlation between dose and tumor response in the radiotherapy of lung cancer of various histological types

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Koga, Kenji; Kusuhara, Toshiyuki; Nishikawa, Kiyoshi; Asada, Keiko; Watanabe, Katsushi

1984-01-01

Correlation between dose and tumor response by cell types was determined in 50 patients with lung cancer in order to predict the possibility of further tumor regression. The TDF (time-dose-fractionation) concept was used as dose factor. The radiation source was a cobalt-60 γ-ray or linear accelerator 10 MV X-ray. As a routine regime a fraction dose of 2 Gy five times per week was given to 39 of the 50 patients, but a dose of 2 Gy three times per week or of 1.5 Gy five times per week was given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma and better in adenocarcinoma than in squamous cell carcinoma, showing a tumor regression rate of 50% or more in 90%, 80% and 58% of the patients, respectively. The correlation between tumor regression rate and TDF values was good in squamous cell carcinoma (r = 0.73) and small cell carcinoma (r = - 0.72), but poor in adenocarcinoma (r = - 0.10). These results suggest that in squamous cell carcinoma improvement of tumor regression can be expected by increasing TDF values, and in adenocarcinoma and small cell carcinoma the optimal TDF values are about 100 and 60 to 80, respectively. (author)

Time-dependent cell disintegration kinetics in lung tumors after irradiation

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Chvetsov, Alexei V; Palta, Jatinder J [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Nagata, Yasushi [Department of Therapeutic Radiology and Oncology, Kyoto University, Kyoto (Japan)], E-mail: chvetsov@ufl.edu

2008-05-07

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T{sub 1/2}. The half-life T{sub 1/2} is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T{sub 1/2} of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations.

Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder

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Graham, Donna M.; O’Connor, Kate M.; Hinchion, John; Coate, Linda E.; Burke, Louise; Power, Derek G.

2013-01-01

Background Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. Case report We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. Conclusion This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours. PMID:24936321

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

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Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

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The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

Wedge resection and segmentectomy in patients with stage I non-small cell lung carcinoma

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Konstantinos Reveliotis

2014-09-01

Full Text Available The use of sublobar resections as definitive management in stage I non-small cell lung carcinoma is a controversial topic in the medical community. We intend to report the latest developments and trends in relative indications for each of the above-mentioned surgical approaches for the treatment of stage I non-small cell lung carcinoma as well as the results of studies regarding local recurrence, disease-free survival and five-year survival rates. We reviewed 45 prospective and retrospective studies conducted over the last 25 years listed in the Pubmed and Scopus electronic databases. Trials were identified through bibliographies and a manual search in journals. Authors, citations, objectives and results were extracted. No meta-analysis was performed. Validation of results was discussed. Segmentectomies are superior to wedge resections in terms of local recurrences and cancer-related mortality rates. Sublobar resections are superior to lobectomy in preserving the pulmonary parenchyma. High-risk patients should undergo segmentectomy, whereas lobectomies are superior to segmentectomies only for tumors >2 cm (T2bN0M0 in terms of disease-free and overall 5-year survival. In most studies no significant differences were found in tumors <2 cm. Disease-free surgical margins are crucial to prevent local recurrences. Systematic lymphadenectomy is mandatory regardless of the type of resection used. In sublobar resections with less thorough nodal dissections, adjuvant radiotherapy can be used. This approach is preferable in case of prior resection. In pure bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are associated with a shorter hospital stay. The selection of the type of resection in T1aN0M0 tumors should depend on characteristic of the patient and the tumor. Patient age, cardiopulmonary reserve and tumor size are the most important factors to be considered. However further prospective randomized trials are needed to

Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma.

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Sabater-Marco, Vicente; García-García, José Angel; Roig-Vila, José Vicente

2013-08-01

The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61-year-old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein-Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography-guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene alterations in radiation-induced F344 rat lung tumors

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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

A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

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Roussos Charis

2009-12-01

Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

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2017-08-01

AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung Carcinomas

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Jason H. Gill

2004-11-01

Full Text Available Matrix metalloproteinase (MMP-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC. Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

Time course of development of metastasis in irradiated Lewis lung carcinoma

International Nuclear Information System (INIS)

Ohizumi, Yukio; Maezawa, Hiroshi; Mori, Tomoyuki

1988-01-01

The influence of local irradiation on the development of metastases and primary tumor volume was studied in Lewis lung carcinoma growing intramuscularly in the hind leg of C57BL/6 mice. The time course of development of metastases was determined from the size of the lung colonies at autopsy by determining the growth rate of the colonies. Irradiation within five days after tumor cell injection inhibited the incidence of metastases in accordance with irradiation dose. For irradiation more than seven days after the injection, promotion of metastases was observed around the time of the experiment as a function of irradiation dose and tumor volume. After the irradiation phase, the development of metastases was inhibited in accordance with radiation dose. When delay in metastasis was defined as additional days needed to develop two or ten colonies compared with controls, the relationship between delay and dose was linear. At the regrowth phase of the primary tumor, the incidence of metastases from the irradiated tumor was reduced in comparison with that from unirradiated tumors of the same size. Inhibition of metastases was observed only at 5 Gy and showed slight dose-dependency. Mechanisms in the development of metastases as they related to these findings are also discussed. (autho)

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

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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.)

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.)

GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

Science.gov (United States)

Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

2013-01-18

Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

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. "9"9"mTc-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 "9"9"mTc-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 "9"9"mTc-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

Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse

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Kimura Shioko

2012-12-01

Full Text Available Abstract Background The CCAAT/enhancer binding proteins (C/EBPs play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. Methods A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined. Results A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse. Conclusions The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

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Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

Dramatic Tumor Shrinkage of Locally Advanced and Inoperable Adenoid Cystic Carcinoma after Intra-arterial Chemotherapy

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Fu-Jen Hsueh

2015-06-01

Full Text Available Adenoid cystic carcinoma is rare and usually arises in the salivary glands. It grows slowly, but is characterized by easy perineural invasion with local infiltration and distant metastasis. In metastatic setting, the efficacy of intravenous chemotherapy is limited. Herein, we report one male patient who had a advanced, inoperable adenoid cystic carcinoma with lung metastasis, presenting with right buccal unhealed ulcer, pain and poor intake, whose loco-regional tumors responded dramatically after intra-arterial chemotherapy and his symptoms were almost completely relieved. We also make a literature review for treatment of adenoid cystic carcinoma.

File list: Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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Collision tumor of the thyroid: follicular variant of papillary carcinoma and squamous carcinoma

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Kane Subhadra V

2006-09-01

Full Text Available Abstract Background Collision tumors of the thyroid gland are a rare entity. We present a case of a follicular variant of papillary carcinoma and squamous carcinoma in the thyroid. To the best of our knowledge, this is the first documentation of a collision tumor with a papillary carcinoma and a squamous carcinoma within the thyroid gland. The clinicopathological features and immunohistochemical profile are reported. The theories of origin, epidemiology and management are discussed with a literature review. Case presentation A 65 year old woman presented with a large thyroid swelling of 10 years duration and with swellings on the back and scalp which were diagnosed to be a follicular variant of papillary thyroid carcinoma with metastasis. Clinical examination, radiology and endoscopy ruled out any other abnormality of the upper aerodigestive tract. The patient was treated surgically with a total thyroidectomy with central compartment clearance and bilateral selective neck dissections. The histopathology revealed a collision tumor with components of both a follicular variant of papillary carcinoma and a squamous carcinoma. Immunohistochemical analysis confirmed the independent origin of these two primary tumors. Adjuvant radio iodine therapy directed toward the follicular derived component of the thyroid tumor and external beam radiotherapy for the squamous component was planned. Conclusion Collision tumors of the thyroid gland pose a diagnostic as well as therapeutic challenge. Metastasis from distant organs and contiguous primary tumors should be excluded. The origins of squamous cancer in the thyroid gland must be established to support the true evolution of a collision tumor and to plan treatment. Treatment for collision tumors depends upon the combination of primary tumors involved and each component of the combination should be treated like an independent primary. The reporting of similar cases with longer follow-up will help define the

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Lifescience Database Archive (English)

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File list: DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

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Linghan Jia

Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

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

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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.

Different Response to Nivolumab in a Patient with Synchronous Double Primary Carcinomas of Hypopharyngeal Cancer and Non-Small-Cell Lung Cancer

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Teppei Yamaguchi

2017-09-01

Full Text Available Nivolumab is a humanized IgG4 and programmed death 1 (PD-1 monoclonal antibody that has demonstrated antitumor efficacy in clinical trials of various malignant tumors including non-small-cell lung cancer and head and neck squamous cell carcinoma (SCC. However, patients with multiple primary malignancies were excluded in clinical trials. Thus, the efficacy of nivolumab in such patients has not been revealed yet. The programmed death ligand 1 (PD-L1 expression level is currently the main predictive biomarker of PD-1 inhibitors in various types of solid tumors and hematological malignancies. Here we describe a patient with synchronous double primary carcinomas of hypopharyngeal SCC and lung adenocarcinoma who exhibited different responses to nivolumab. After nivolumab treatment, hypopharyngeal SCC with moderate PD-L1 positivity by immunohistochemical staining showed a remarkable response; conversely, nivolumab was not effective against lung adenocarcinoma, which was negative for PD-L1. This suggests that tumors with different PD-L1 expressions may exhibit different responses to PD-1 inhibitors when multiple primary malignancies are present within one patient.

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

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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.

Enhanced tumor growth in the remaining lung after major lung resection.

Science.gov (United States)

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

2016-05-01

Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuro-endocrine carcinoma of lung

International Nuclear Information System (INIS)

Castillo P, Luis Fernando; Restrepo Uribe, Santiago

1996-01-01

Review of a case of pathologically proven neuroendocrine tumour of the lung, with clinical and radiological correlation. The case of a young patient is presented that in the first month, it presents two episodes of pneumonitis of the superior lobe from the left lung to the one who after the imagenologic studies and pathological practiced, it was made the diagnose definitive of tumor carcinoid of the lung. Due to the drop incidence in the presentation of this type of tumors in the lung, a revision of the general aspects so much is made clinical as pathological, as well as of the discoveries but important from the imagenologic point of view

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

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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.

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

File list: His.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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Usefulness of SCC-antigen for diagnosis and monitoring recurrence and effectiveness of therapies of squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Mino, Naoko; Iio, Atsushi; Ata, Mariko; Murase, Kenya; Kataoka, Masaaki; Ito, Hisao; Ishine, Masahiro; Kawamura, Masashi; Hamamoto, Ken

1987-01-01

The serum levels of SCC antigen (squamous cell carcinoma related antigen) were measured in 111 patients with primary lung cancer to assess its clinical usefulness for diagnosis of squamous cell carcinoma and for monitoring recurrence and effectiveness of therapies. Serum SCC antigen level in patients with squamous cell carcinoma of the lung was 5.9 ± 10.4 ng/ml, which was high (p < 0.05) compared with those in normal controls (1.6 ± 0.5 ng/ml), patients with other types of lung cancer (2.4 ± 2.9 ng/ml) or benign disease (1.8 ± 1.1 ng/ml). Studies at various clinical stages of squamous cell carcinoma of the lung showed, however, that the SCC antigen levels were high only in the advanced stages (III and IV), whereas not so high in the earlier stages. These results confirmed that SCC antigen is a relatively specific marker to squamous cell carcinoma in the lung, as reported in the uterine cervix and the esophagus. The SCC antigen levels decreased after operation and more markedly after radiotherapy in dose-dependent manner, corresponding to the reduction of the tumor size. On the other hand, the SCC antigen levels were extremely high in the recurrence. It was concluded that SCC antigen is a useful marker for monitoring recurrence or effectiveness of the therapies of SCC of the lung, although not so for its early diagnosis. (author)

Carcinoma ex mixed tumor arising in the parotid gland

International Nuclear Information System (INIS)

Choi, Y. S.; Hwang, E. H.; Lee, S. R.

2000-01-01

Carcinoma ex mixed tumor is a mixed tumor in which a second neoplasm develops from the epithelial component that fulfills the criteria for malignancy. This tumor occurs frequently in the parotid glands. Individuals in whom carcinoma ex mixed tumor have a past history of benign mixed tumor. These lesions contain both a benign mixed tumor as well as a malignant neoplasm. We report a case of carcinoma ex mixed tumor which occurred in the parotid gland. A 67-year-old woman presented with movable right mass. She complained pain and facial paralysis. The clinical presentation, several diagnostic images, and histopathologic findings are presented.

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File list: NoD.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: NoD.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

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

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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.

Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells.

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Yamauchi, Yoshikane; Izumi, Yotaro; Asakura, Keisuke; Kawai, Kenji; Wakui, Masatoshi; Ohmura, Mitsuyo; Suematsu, Makoto; Nomori, Hiroaki

2013-09-01

The interactions of tumor cells with stromal fibroblasts influence tumor biology, but the exact mechanisms involved are still unclear. In the present study, we evaluated the effects of a human lung fibroblast cell line, TIG-3, on Lewis lung carcinoma (LLC) cells both in vitro and in vivo. LLC and TIG-3 cells were co-cultured/co-implanted in vitro and in vivo. Cell invasion was assayed. Local tumor growth, as well as lung metastasis, were evaluated after subcutaneous cell co-implantation into NOD/SCID/γ-null (NOG) mice. LLC, and TIG-3 cells were pre-treated with either SB431542, a small molecule TGF-β receptor antagonist, or siRNA for transforming growth factor (TGF)-β before co-culture or co-implantation, and the effects of pre-treatments were compared both in cell culture and in mice. Subcutaneous LLC tumor growth (L group) in NOG mice was significantly increased by co-implantation of TIG-3 cells (L+T group) at four weeks. The number of macroscopic lung metastases was also significantly increased in the L+T group in comparison to the L group. In vitro cell invasion was significantly increased in the L+T group in comparison to the L group. In vitro expression of phosphorylated-SMAD3 was significantly increased in the L+T group in comparison to the L group. Furthermore, pre-treatment with either SB431542 or siRNA for TGF-β reduced the invasiveness both in culture and in mice. This study suggested that in vitro as well as in vivo progression of LLC was facilitated by co-culture/co-implantation with TIG-3 cells, and that this process was at least in part dependent on TGF-β-mediated interactions.

Tumorous interstitial lung disease

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Dinkel, E.; Meyer, E.; Mundinger, A.; Helwig, A.; Blum, U.; Wuertemberger, G.

1990-01-01

The radiological findings in pulmonary lymphangitic carcinomatosis and in leukemic pulmonary infiltrates mirror the tumor-dependent monomorphic interstitial pathology of lung parenchyma. It is a proven fact that pulmonary lymphangitic carcinomatosis is caused by hematogenous tumor embolization to the lungs; pathogenesis by contiguous lymphangitic spread is the exception. High-resolution CT performed as a supplement to the radiological work-up improves the sensitivity for pulmonary infiltrates in general and thus makes the differential diagnosis decided easier. Radiological criteria cannot discriminate the different forms of leukemia. Plain chest X-ray allows the diagnosis of pulmonary involvement in leukemia due to tumorous infiltrates and of tumor- or therapy-induced complications. It is essential that the radiological findings be interpreted with reference to the stage of tumor disease and the clinical parameters to make the radiological differential diagnosis of opportunistic infections more reliable. (orig.) [de

A Comparative Study of Primary Adenoid Cystic and Mucoepidermoid Carcinoma of Lung

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Vivek Kumar

2018-05-01

Full Text Available BackgroundPulmonary mucoepidermoid carcinoma (PMEC and pulmonary adenoid cystic carcinoma (PACC are the two major types of primary salivary gland-type (PSGT lung cancers. The demographic profile, clinicopathological features, and predictors of survival as an overall group have not been described for PSGT cancers of lung.MethodsIn this study, we analyzed demographic, clinical, and survival data from 1,032 patients (546 PMEC and 486 PACC who were diagnosed of PSGT lung cancer in the Surveillance, Epidemiology and End Results database from 1973 to 2014.ResultsThe PSGT constituted 0.09% of all lung cancers with age-adjusted incidence rate of 0.07 per 100,000 person-years and change of −32% from 1973 to 2014. The incidence of PMEC was slightly higher than PACC but there were no differences in the age and sex distribution. PACCs (55% were significantly higher at trachea and main bronchus while PMECs were more common at peripheral lungs (85%. Most of the tumors were diagnosed at an early stage and were low grade irrespective of histology. As compared to PMEC, significantly higher number of patients with PACC underwent radical surgery and received adjuvant radiation. The 1- and 5-year cause-specific survival was 76.6 and 62.8%, respectively. On multivariate analysis, the survival was affected by age at diagnosis, tumor stage, histological grade, period of diagnosis, and surgical resection. The histology showed strong interaction with time and hazard ratio of patients with PACC was significantly worse than patients with PMEC only after 5 years.ConclusionThe incidence of pulmonary PSGT cancer is 7 cases per 10 million population in the United States and is decreasing. There was no difference between demographic profile of patients with PMEC and PACC but pathological features were diverse. The difference in the survival of patients with the two histological types surfaced only after 5 years when survival of patients with PMEC was better than PACC.

v-Ha-ras oncogene insertion: A model for tumor progression of human small cell lung cancer

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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

[Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].

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Ma, Sheng-lin; Feng, Jian-guo; Gu, Lin-hui; Ling, Yu-tian

2003-03-01

To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied. Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST. 1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable. D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.

Circulating tumor cells in lung cancer.

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Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

2012-01-01

Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

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

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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.

Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

International Nuclear Information System (INIS)

Zamora, P.O.; Bender, H.; Biersack, H.J.; Knapp, F.F. Jr.

1995-01-01

The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 can be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity

Radiosensitization of normoxic and hypoxic h1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1α.

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Schilling, Daniela; Bayer, Christine; Li, Wei; Molls, Michael; Vaupel, Peter; Multhoff, Gabriele

2012-01-01

Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia inducible factor-1α (HIF-1α). Overexpression of HIF-1α is assumed to promote malignant transformation and tumor progression and thus might reduce the accessibility to radiotherapy. Herein, we describe the effects of the novel Hsp90 inhibitor NVP-AUY922 and 17-allylamino-17-demethoxygeldanamycin (17-AAG), as a control, on HIF-1α levels and radiosensitivity of lung carcinoma cells under normoxic and hypoxic conditions. NVP-AUY922 exhibited a similar biological activity to that of 17-AAG, but at only 1/10 of the dose. As expected, both inhibitors reduced basal and hypoxia-induced HIF-1α levels in EPLC-272H lung carcinoma cells. However, despite a down-regulation of HIF-1α upon Hsp90 inhibition, sensitivity towards irradiation remained unaltered in EPLC-272H cells under normoxic and hypoxic conditions. In contrast, treatment of H1339 lung carcinoma cells with NVP-AUY922 and 17-AAG resulted in a significant up-regulation of their initially high HIF-1α levels and a concomitant increase in radiosensitivity. In summary, our data show a HIF-1α-independent radiosensitization of normoxic and hypoxic H1339 lung cancer cells by Hsp90 inhibition.

CAFET algorithm reveals Wnt/PCP signature in lung squamous cell carcinoma.

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Yue Hu

Full Text Available We analyzed the gene expression patterns of 138 Non-Small Cell Lung Cancer (NSCLC samples and developed a new algorithm called Coverage Analysis with Fisher's Exact Test (CAFET to identify molecular pathways that are differentially activated in squamous cell carcinoma (SCC and adenocarcinoma (AC subtypes. Analysis of the lung cancer samples demonstrated hierarchical clustering according to the histological subtype and revealed a strong enrichment for the Wnt signaling pathway components in the cluster consisting predominantly of SCC samples. The specific gene expression pattern observed correlated with enhanced activation of the Wnt Planar Cell Polarity (PCP pathway and inhibition of the canonical Wnt signaling branch. Further real time RT-PCR follow-up with additional primary tumor samples and lung cancer cell lines confirmed enrichment of Wnt/PCP pathway associated genes in the SCC subtype. Dysregulation of the canonical Wnt pathway, characterized by increased levels of β-catenin and epigenetic silencing of negative regulators, has been reported in adenocarcinoma of the lung. Our results suggest that SCC and AC utilize different branches of the Wnt pathway during oncogenesis.

Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

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Kolson Kokohaare, Eva; Riva, Francesco M G; Bernstein, Jonathan M; Miah, Aisha B; Thway, Khin

2018-04-01

We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy

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Cem Gundogdu

2011-07-01

Full Text Available Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0,2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28th week of pregnancy. Patient was delivered with sectio abdominale at the 39th week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature.

The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations.

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Nicola Fusco

Full Text Available Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

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Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

2015-01-01

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

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Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

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.

Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

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G-Andre Banat

Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

Primitive neuroectodermal tumor or small cell carcinoma of the kidney, arare neoplasm: Case Report

International Nuclear Information System (INIS)

Radhi, A.; Ratnakar, K.S.; Al-Durazi, M.; Khalifa, F.

2002-01-01

Small cell carcinoma is a malignancy primarily recognized in thebronchopulmonary region. Extrapulmonary locations are extremely uncommon. Wereport here a case of renal tumor encountered in a 34-year-old female, withextensive metastases in liver, lung and bone. Histological examination wasmost compatible with primitive neuroectodermal tumor (PNET) small cellcarcinoma. There were negative immunohistochemical markers for cytokeratin,any hormonal peptides and epithelial membrane antigens, which is consistentwith the designation of neoplasm as PNET. Previously reported cases have allbeen in the elderly and, to the best of our knowledge, this is the first caseof proven PNET of the kidney described in a young female. (author)

NUT midline carcinoma mimicking a germ cell tumor: a case report

International Nuclear Information System (INIS)

Harada, Yohei; Koyama, Takafumi; Takeuchi, Kengo; Shoji, Kazufusa; Hoshi, Kazuei; Oyama, Yu

2016-01-01

NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor. A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC. Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18 F-FDG PET/CT is useful for staging and assessing responses to therapy

A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

Science.gov (United States)

Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

2017-03-01

Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

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

MS4A1 dysregulation in asbestos-related lung squamous cell carcinoma is due to CD20 stromal lymphocyte expression.

Directory of Open Access Journals (Sweden)

Casey M Wright

Full Text Available Asbestos-related lung cancer accounts for 4-12% of lung cancers worldwide. We have previously identified ADAM28 as a putative oncogene involved in asbestos-related lung adenocarcinoma (ARLC-AC. We hypothesised that similarly gene expression profiling of asbestos-related lung squamous cell carcinomas (ARLC-SCC may identify candidate oncogenes for ARLC-SCC. We undertook a microarray gene expression study in 56 subjects; 26 ARLC-SCC (defined as lung asbestos body (AB counts >20AB/gram wet weight (gww and 30 non-asbestos related lung squamous cell carcinoma (NARLC-SCC; no detectable lung asbestos bodies; 0AB/gww. Microarray and bioinformatics analysis identified six candidate genes differentially expressed between ARLC-SCC and NARLC-SCC based on statistical significance (p2-fold. Two genes MS4A1 and CARD18, were technically replicated by qRT-PCR and showed consistent directional changes. As we also found MS4A1 to be overexpressed in ARLC-ACs, we selected this gene for biological validation in independent test sets (one internal, and one external dataset (2 primary tumor sets. MS4A1 RNA expression dysregulation was validated in the external dataset but not in our internal dataset, likely due to the small sample size in the test set as immunohistochemical (IHC staining for MS4A1 (CD20 showed that protein expression localized predominantly to stromal lymphocytes rather than tumor cells in ARLC-SCC. We conclude that differential expression of MS4A1 in this comparative gene expression study of ARLC-SCC versus NARLC-SCC is a stromal signal of uncertain significance, and an example of the rationale for tumor cell enrichment in preparation for gene expression studies where the aim is to identify markers of particular tumor phenotypes. Finally, our study failed to identify any strong gene candidates whose expression serves as a marker of asbestos etiology. Future research is required to determine the role of stromal lymphocyte MS4A1 dysregulation in

Tumor-associated macrophages: Oblivious confederates in invasive mammary carcinoma

Directory of Open Access Journals (Sweden)

Imtiaz Ahmed

2017-01-01

Full Text Available Background: The infiltrating margins of carcinomas are associated with presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Amongst the inflammatory cells, Tumor Associated Macrophages (TAMs play a key role in the tumorigenesis. This study elucidates the density of TAMs in invasive mammary carcinomas and attempts to establish aa association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Materials and Methods: 90 diagnosed archival cases of invasive mammary carcinomas at a tertiary care centre were included. Density of TAMs was assessed by using CD68 which is a pan-macrophage marker by immunohistochemistry on the archival tissue blocks. The density TAMs (CD68 positive cells was dichotomised into high (>50 CD68 positive cells/ HPF and low (<5050 CD68 positive cells/ HPF and compared with the above mentioned pathological variables using appropriate statistical tests. Results: The density of TAMs was significantly higher around the infiltrating edge of the carcinoma in comparison to the adjoining normal terminal duct lobular units. The density of TAMs was more in the infiltrating edge of the tumor than within the tumor nodule/nests. A higher TAM density showed a significant association in tumors having large tumor size, higher histological grade, nodal metastasis, absence of ER and PR expression and Her2Neu overexpression (p value <0.05. Conclusion: TAMs play an important role in tumor progression in invasive mammary carcinomas. This is as a result of the multiple roles enacted by TAMs in the various stages of tumor development starting from tumor growth, invasion, angiogenesis and metastases. Targeted therapy against TAMs has great potential in the being important components of future treatment strategies against breast carcinomas.

[Pulmonary sarcomatoid carcinoma].

Science.gov (United States)

Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

2016-01-01

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics. Copyright © 2016. Published by Elsevier Masson SAS.

Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells.

Science.gov (United States)

Zhang, Zhi-Dong; Liang, Kai; Li, Kun; Wang, Guo-Quan; Zhang, Ke-Wei; Cai, Lei; Zhai, Shui-Ting; Chou, Kuo-Chen

2017-01-01

Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has been widely used as a food supplement and reported to have antioxidant and anticancer properties. The current study was designed to assess the cytotoxic, apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. A549 cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at various concentrations (0-300 μg/ml) for 24 hr. The comet assay and γH2AX assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells. Chlorella vulgaris hot water extract induced apoptosis and DNA damage in human lung carcinoma cells. CGF can thus be considered a potential cytotoxic or genotoxic drug for treatment of lung carcinoma. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mucoepidermoid Lung Carcinoma in Child

African Journals Online (AJOL)

usually includes asthma, pneumonia, atelectasis, middle lobe syndrome and pleural effusion. Recurrent pneumonia in the same region of the lung should raise clinical suspicion of an endobronchial lesion or mass, such as mucoepidermoid carcinoma.[1] Because MECs are most commonly found in the segmental or lobar ...

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.

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.

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.

Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma

DEFF Research Database (Denmark)

Helin, K; Holm, K; Niebuhr, A

1997-01-01

107, or p130 leads to growth arrest in the G1 phase of the cell cycle, and this arrest is abolished by complex formation with the adenovirus E1A, human papilloma virus E7, or simian virus 40 T oncoproteins. Inactivation of pRB by gross structural alterations or point mutations in the RB-1 gene has...... been described in a variety of human tumors, including retinoblastomas, osteosarcomas, and small cell lung carcinomas. Despite the structural and functional similarity between pRB, p107, and p130, alterations in the latter two proteins have not been identified in human tumors. We have screened a panel...

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

International Nuclear Information System (INIS)

Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro

1996-01-01

The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P=0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P=0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P=0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P=0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy. (author)

On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

International Nuclear Information System (INIS)

Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

2016-01-01

Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

Primary therapy for cancer of the lung-1985

International Nuclear Information System (INIS)

Cox, J.D.

1987-01-01

The age-adjusted death rates from cancer of the lung have soared in the past 50 years. Radiation therapy has come to have a major role in the management of patients with squamous carcinoma, adenocarcinoma, and large cell carcinoma. Resectable patients who have regional lymph node metastases benefit from postoperative irradiation. For those with unresectable tumors, radiation therapy is the only definitive, potentially curative treatment. Control of the intrathoracic tumor is a major determinant of survival in these patients, so all efforts to achieve maximum control of the local regional tumor are justified. The most important determinant of control of the intrathoracic tumor is the biologic dose of radiations. In patients with small cell carcinoma, chemotherapy employing at least three effective drugs is an essential part of the management. Prophylactic cranial irradiation reduces the frequency of brain metastasis although extracranial CNS metastases may still occur. Thoracic irradiation increases the probability of controlling the tumor that is usually most bulky and it increases long-term survival. Patients with cancer of the lung of any histopathologic type benefit from palliative irradiation of metastases that produce pain or compromise vital structures. Initial performance status is the single most important prognostic factor in patients with carcinoma of the lung. Prognosis has improved during the last decade for patients with inoperable tumors as a result of improvement in radiotherapeutic technique and the use of systemic chemotherapy for small cell carcinoma

[Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

Science.gov (United States)

Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

2016-04-20

Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (Pdifference by

Recommendations for standardized diagnostics, treatment and following care in tumor diseases

International Nuclear Information System (INIS)

2001-01-01

The paper present a series of articles developed by the specialized groups from various clinical and research sections of the Tumorzentrum Heidelberg/Mannheim. It consists of 10 volumes, as following: vol. 1 Early diagnosis. Diagnosis and therapy of cancer pains. Care by the family doctor. Geriatric patient with tumor disease; vol. 2 Breast carcinoma. Ovary carcinoma; vol. 3 Malignant tumors of salivary glands. Malignant tumors of larynx and pharynx; vol. 4 Thyroid carcinoma. Tumors of pituitary gland; 5. Malignant tumors of lung, pleura and thymus gland. Pancreas carcinoma. Hodgkins disease. Chronic myelo-proliferative diseases; 6. Rectum carcinoma. Colon carcinoma; 7. Prostate carcinoma. Malignant tumors of the urinary tract; 8. Brain tumors - gliomas and metastases; 9. Primary malignant tumors of bones. Tissue sarcomas in adults. 10. Stomach carcinoma

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.

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.

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

Science.gov (United States)

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

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.

“Marker of Self” CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors

Directory of Open Access Journals (Sweden)

Nisha G Sosale

2016-01-01

Full Text Available Lentiviruses infect many cell types and are now widely used for gene delivery in vitro, but in vivo uptake of these foreign vectors by macrophages is a limitation. Lentivectors are produced here from packaging cells that overexpress “Marker of Self” CD47, which inhibits macrophage uptake of cells when prophagocytic factors are also displayed. Single particle analyses show “hCD47-Lenti” display properly oriented human-CD47 for interactions with the macrophage's inhibitory receptor SIRPA. Macrophages derived from human and NOD/SCID/Il2rg−/− (NSG mice show a SIRPA-dependent decrease in transduction, i.e., transgene expression, by hCD47-Lenti compared to control Lenti. Consistent with known “Self” signaling pathways, macrophage transduction by control Lenti is decreased by drug inhibition of Myosin-II to the same levels as hCD47-Lenti. In contrast, human lung carcinoma cells express SIRPA and use it to enhance transduction by hCD47-Lenti- as illustrated by more efficient gene deletion using CRISPR/Cas9. Intravenous injection of hCD47-Lenti into NSG mice shows hCD47 prolongs circulation, unless a blocking anti-SIRPA is preinjected. In vivo transduction of spleen and liver macrophages also decreases for hCD47-Lenti while transduction of lung carcinoma xenografts increases. hCD47 could be useful when macrophage uptake is limiting on other viral vectors that are emerging in cancer treatments (e.g., Measles glycoprotein-pseudotyped lentivectors and also in targeting various SIRPA-expressing tumors such as glioblastomas.

Neuroendocrine carcinomas of the lung

International Nuclear Information System (INIS)

Forster, B.B.; Muller, N.L.; Miller, R.R.; Nelems, B.; Evans, K.G.

1988-01-01

Neuroendocrine lung carcinomas may be classified as Kulchitzky cell carcinoma (KCC) I (classic carcinoids), II (atypical carcinoids), and III (small cell carcinomas). The authors reviewed the clinical, CT, and pathologic findings in 31 patients with KCC. KCC I occurred mainly in younger nonsmoking women, and on CT were small (1.8 cm average diameter) and showed lymphadenopathy in one of ten patients. KCC II were found mainly in older smoking men and were larger (3.9 cm, P < .001), and four of ten patients had lymphadenopathy. KCC III occurred in older smoking men and were large (4.2 cm), and 11 of 11 patients had lymphadenopathy. Sputum cytology and percutaneous and bronchoscopic biopsy were often nondiagnostic or misleading. The authors conclude that chest CT provides additional discriminating information in the preoperative diagnosis of KCC

A case of squamous cell lung cancer after treating with radiation for small cell lung cancer

International Nuclear Information System (INIS)

Hayashi, Toshinari; Ide, Hiroshi; Siomi, Katsuhiko; Nakamura, Yukinobu; Tada, Shinya; Kageyama, Hiroshi; Kido, Masamitsu

1999-01-01

A 77-year-old man was admitted due to an abnormal shadow on a chest X-ray film in September 1993. Small cell lung cancer was diagnosed by transbronchial lung biopsy of left S 3 . Because of his pulmonary and renal dysfunction, he received only 40 Gy irradiation alone, and the tumor shadow disappeared. After 38 months' observation, a new nodular shadow was detected in the left upper lung field in March 1997. A tumor was found in left B 3 by bronchoscopy, and biopsy revealed squamous cell carcinoma. Because of his advanced age and hypoxia, he has had no active treatment. This was a rare case of small cell lung cancer with long term survival, treated only by radiation, in which a different histologic type of carcinoma appeared in the same radiation field. (author)

Calcification in large cell neuroendocrine carcinoma of the lung

International Nuclear Information System (INIS)

Takamochi, Kazuya; Yokose, Tomoyuki; Ochiai, Atsushi; Yoshida, Junji; Nishimura, Mitsuyo; Ohmatsu, Hironobu; Nagai, Kanji; Nishiwaki, Yutaka

2003-01-01

The aim was to investigate the prevalence of intratumoral calcification in large cell neuroendocrine carcinoma (LCNEC) and to review computed tomography (CT) and histological findings. From August 1992 through March 2000, 35 out of 1183 surgically resected lung cancer patients were histologically diagnosed as having LCNEC at our institute. We reviewed the pain radiographs and CT scans of these 35 LCNEC patients. In LCNEC cases with intratumoral calcification, we examined the size, number, distribution and pattern of intratumoral calcifications visible on the CT scans and the histological features. Three cases (9%) exhibited calcification. The calcifications were recognized by CT scans alone. The CT scans showed punctate or eccentric intratumoral calcifications, which are considered to be a malignant feature, in all three cases. In two cases, the calcifications were histologically confirmed to be located within the necrotic areas of a tumor nest. We found three LCNEC cases with intratumoral calcification. The prevalence of LCNEC calcification was similar to that in previous reports on lung cancer. The mechanism of the intratumoral calcification in our LCNEC cases is speculated to be dystrophic calcification. (author)

Tumor Seeding Following Lung Radiofrequency Ablation: A Case Report

International Nuclear Information System (INIS)

Yamakado, Koichiro; Akeboshi, Masao; Nakatsuka, Atsuhiro; Takaki, Haruyuki; Takao, Motoshi; Kobayashi, Hiroyasu; Taguchi, Osamu; Takeda, Kan

2005-01-01

Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy

Collision tumor of Small Cell Carcinoma and Squamous Cell Carcinoma of maxillary sinus

Directory of Open Access Journals (Sweden)

Irfan Sugianto

2016-06-01

Full Text Available Two kinds of different malignant tumors occurring within the same organ is defined as collision tumor. Small Cell Carcinoma (SmCC is high-grade derived from neuroendocrine cell tumors, occurance in the head and neck is rare. Squamous Cell Carcinoma (SCC is the most common malignancies encountered in head and neck area, but the occuranceof collision tumor is very rare. This report describe a 82 year-old woman patient with a SmCC and SCC that occurred in the maxillary sinus. CT was performed including with enhancement, MRI examination was T1WI, STIR and contrast enhancement. We also conducted analysis of Dynamic Contrast Enhancement (DCE. Histopathologic examination revealed small cell carcinoma. A distant metastasis was not detected. After patient received chemoradiotherapy (CCRT, most of  tumorwas reduced although a part of the tumor was remained. Pathological examination of surgery tumor specimen revealed that specimen consisted of SCC and SmCC was disappeared, and six months after surgery, the patient suffered tumor recurrence and multiple metastasis to the organs in the abdomen. This time we have to report that the experience one cases that are considered collision cancer of SmCC and SCC that occurred in the maxillary sinus.

Measurement of lung tumor motion using respiration-correlated CT

International Nuclear Information System (INIS)

Mageras, Gig S.; Pevsner, Alex; Yorke, Ellen D.; Rosenzweig, Kenneth E.; Ford, Eric C.; Hertanto, Agung; Larson, Steven M.; Lovelock, D. Michael; Erdi, Yusuf E.; Nehmeh, Sadek A.; Humm, John L.; Ling, C. Clifton

2004-01-01

Purpose: We investigate the characteristics of lung tumor motion measured with respiration-correlated computed tomography (RCCT) and examine the method's applicability to radiotherapy planning and treatment. Methods and materials: Six patients treated for non-small-cell lung carcinoma received a helical single-slice computed tomography (CT) scan with a slow couch movement (1 mm/s), while simultaneously respiration is recorded with an external position-sensitive monitor. Another 6 patients receive a 4-slice CT scan in a cine mode, in which sequential images are acquired for a complete respiratory cycle at each couch position while respiration is recorded. The images are retrospectively resorted into different respiration phases as measured with the external monitor (4-slice data) or patient surface displacement observed in the images (single-slice data). The gross tumor volume (GTV) in lung is delineated at one phase and serves as a visual guide for delineation at other phases. Interfractional GTV variation is estimated by scaling diaphragm position variations measured in gated radiographs at treatment with the ratio of GTV:diaphragm displacement observed in the RCCT data. Results: Seven out of 12 patients show GTV displacement with respiration of more than 1 cm, primarily in the superior-inferior (SI) direction; 2 patients show anterior-posterior displacement of more than 1 cm. In all cases, extremes in GTV position in the SI direction are consistent with externally measured extremes in respiration. Three patients show evidence of hysteresis in GTV motion, in which the tumor trajectory is displaced 0.2 to 0.5 cm anteriorly during expiration relative to inspiration. Significant (>1 cm) expansion of the GTV in the SI direction with respiration is observed in 1 patient. Estimated intrafractional GTV motion for gated treatment at end expiration is 0.6 cm or less in all cases; however; interfraction variation estimates (systematic plus random) are more than 1 cm in 3

Antitumor effect of cordycepin (3'-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation.

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Nakamura, Kazuki; Yoshikawa, Noriko; Yamaguchi, Yu; Kagota, Satomi; Shinozuka, Kazumasa; Kunitomo, Masaru

2006-01-01

An attempt was made to elucidate the molecular targetfor the antitumor effects of cordycepin (3'-deoxyadenosine) using non-selective and selective adenosine A1, A2a, A2b and A3 receptor agonists and antagonists. Although adenosine and 2'-deoxyadenosine (up to 100 microM) had no effect, cordycepin showed remarkable inhibitory effects on the growth curves of B16-BL6 mouse melanoma (IC50= 39 microM) and mouse Lewis lung carcinoma (IC50 = 48 microM) cell lines in vitro. Among the adenosine receptor agonists and antagonists used (up to 100 microM), only 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective adenosine A3 receptor agonist, notably inhibited the growth of both mouse tumor cell lines (B16-BL6; IC50 = 5 microM, LLC; 14 microM). In addition, the tumor growth inhibitory effect of cordycepin was antagonized by 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191), a selective adenosine A3 receptor antagonist. These results suggest that cordycepin exerts inhibitory effects on the growth of mouse melanoma and lung carcinoma cells by stimulating adenosine A3 receptors on tumor cells.

Co-expression of podoplanin and fibroblast growth factor 1 predicts poor prognosis in patients with lung squamous cell carcinoma.

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Li, Juan; Chen, Han; Li, Xiaoqing; Wang, Linlin; Gao, Aiqin; Zhang, Pei; Lin, Wenli; Gao, Wei; Yang, Dong; Guo, Xiaosun; Liu, Jie; Dang, Qi; Sun, Yuping

2017-08-01

Podoplanin and fibroblast growth factor (FGF) 1 have been detected more frequently in lung squamous cell carcinoma (SQCC) compared with lung adenocarcinoma. Furthermore, it has been previous demonstrated that FGF1 is located on the edge of tumor nests in certain lung SQCC sections, which resembles the characteristic expression pattern of podoplanin. Podoplanin and FGF1 have roles in lymphangiogenesis and angiogenesis. Based on their consistently specific expression in lung SQCC and similar localization patterns, the present study aimed to investigate whether the expression of podoplanin in tumor cells is correlated with FGF1 expression in lung SQCC and whether their co‑expression has clinicopathological significance, particularly for lymphangiogenesis/angiogenesis. The correlation between podoplanin and FGF1 expression in tumor cells of 82 lung SQCC cases was investigated by immunohistochemical staining and the association between the co‑expression of podoplanin and FGF1, and clinicopathological factors such as microvessel density (MVD), was examined in these samples. In addition, the prognostic value of co‑expression of podoplanin and FGF1 in tumor cells was determined, and the regulation of FGF1 expression and angiogenesis by podoplanin was examined in vitro in a human lung SQCC cell line. Immunohistochemical analysis demonstrated that there was a significant correlation between podoplanin and FGF1 expression in lung SQCC tumor cells (R=0.591; P<0.0001). Co‑expression of podoplanin and FGF1 was significantly associated with larger primary tumor size, advanced TNM stage and higher intratumoral MVD. Survival analysis demonstrated that cases with podoplanin and FGF1 double‑positive staining had a significantly lower survival rate compared with cases with double‑negative staining. In vitro experiments revealed that podoplanin regulated FGF1 expression and affected tube formation of human umbilical vein endothelial cells. Combined, the results

Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base

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A. Murinello

2010-07-01

Full Text Available Based on a case of gastric antral vascular ectasia (watermelon stomach that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma. Resumo: Baseados num caso de gastropatia antral com ectasia vascular (estômago em melancia associado a pericardite hemorrágica e a um carcinoma de pequenas células do pulmão com metástases ganglionares ao longo do mediastino e a um carcinoma pavimentocelular síncrono da base da língua, os autores fazem uma revisão dos aspectos clínicos, endoscópicos e histopatológicos deste tipo de gastropatia, da sua associação a outras doenças e das possibilidades terapêuticas actuais por via endoscópica. Referem-se igualmente as causas mais frequentes de pericardite hemorrágica, salientando-se a necessidade de esclarecer se o derrame é ou não de origem neoplásica. Não está referida na literatura a associação deste tipo de gastropatia ao carcinoma de pequenas células do pulmão nem ao carcinoma pavimento-celular da base da língua. A invasão extensa dos gânglios mediastínicos pelo carcinoma de pequenas células do pulmão é ocorrência frequente. Key-words: Gastric antral vascular ectasia, watermelon stomach, small cell lung carcinoma, oat cell lung carcinoma, squamous cell carcinoma of the base

Squamous cell carcinoma of the esophagus and multiple primary tumors of the upper aerodigestive tract Carcinoma epidermoide do esôfago e múltiplos tumores primários do trato aerodigestivo alto

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Ulysses RIBEIRO Jr.

1999-12-01

Full Text Available Squamous cell carcinoma of the esophagus is frequently associated with other, synchronous or metachronous tumors, in the upper aerodigestive tract. All 264 patients with squamous cell carcinoma of the esophagus, treated in the Gastrointestinal Surgery, Esophagus section, of the "Hospital das Clínicas" (São Paulo University Medical School, Brazil, between 1979 and 1989 were analyzed retrospectively with regards to the occurrence of multiple primary tumors in the upper aerodigestive tract. Multiple primary tumors were encountered in 10 (3.8% patients. All patients were male and the mean age at the time of the first primary was 52.2 years. Tobacco smoke and alcohol were the principal carcinogens in these patients (n = 10. The sites of the tumors were: larynx (n = 4, tongue (n = 4, lung (n = 2, and oral cavity (n = 1. Two simultaneous, three synchronous and five metachronous multiple primary carcinomas were detected. The esophagus was the second primary tumor in nine patients. The mean overall survival after the diagnosis of the second primary was 2.8 months (SD = 0.89. Inquiry regarding other malignancies, associated with panendoscopy should be carry out prior to the treatment of the first primary to diagnose simultaneous or synchronous primary tumors, and careful follow-up should be performed after treatment of the first primary to detect new tumors in these high-risk patients.Carcinoma epidermóide do esôfago está freqüentemente associado a outros, sincrônicos ou metacrônicos tumores do trato aerodigestivo alto. Foram analisados, retrospectivamente, 264 pacientes com carcinoma de esôfago tratados na Disciplina de Cirurgia do Aparelho Digestivo, Divisão de Cirurgia do Esôfago, do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 1979 e 1989, com o intuito de se observar a ocorrência de múltiplos tumores primários do trato aerodigestivo alto. Observaram-se 10 (3.8% pacientes com múltiplos tumores

Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

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Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

2011-01-15

Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

Carcinoma pleomórfico do pulmão em doente com síndroma de Mounier-Kuhn Pleomorphic carcinoma of the lung in a patient with Mounier-Kuhn syndrome

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Daniela Ferreira

2006-09-01

Full Text Available O carcinoma pleomórfico do pulmão (CPP é um tumor maligno raro e de prognóstico reservado. Está inserido no grupo dos carcinomas pulmonares pouco diferenciados não pequenas células, exibe componente sarcomatoso ou sarcoma like (células fusiformes//células gigantes. Atendendo à raridade do tumor e às dificuldades no diagnóstico, é apresentado pelos autores o caso de um carcinoma pleomórfico do pulmão diagnosticado por biópsia aspirativa num paciente de 44 anos, fumador, e cuja apresentação inicial consistiu numa tumefacção dorsal. À data de diagnóstico apresentava estádio IV (TNM, não tendo sido possível efectuar tratamento dirigido ao tumor pelo mau performancestatusapresentado pelo doente, mas apenas terapêutica de suporte. A sobrevida do doente foi de 5 meses. Na sequência do estudo clínico, foi confirmada a síndroma de Mounier-Kuhn. Reportam-se os aspectos clínico-imagiológicos mais importantes, assim como os aspectos citológicos e imunocitoquímicos que caracterizam esta entidade e permitiram efectuar o diagnóstico.Pleomorphic carcinoma of the lung (PLC is a rare malignant tumour presenting with a poor clinical outcome. It is included in the group of non-small cell lung carcinomas that contain sarcoma or sarcoma-like components (spindle cells/giant cells. Because of its rarity and diagnostic difficulties, the authors report a case of PLC in a 44 year-old patient, smoker, with the initial clinical presentation of a dorsal tumoural mass. As the time of diagnosis the tumour was in stage IV (TNM, the patient was treated only with supportive therapy and died five months later. During clinical evaluation, a Mounier-Kuhn Syndrome was confirmed. Clinical-imagiological aspects of this situation are reported as well as cytological and immunocytochemical features.

Stereotactic Body Radiotherapy for Oligometastatic Lung Tumors

International Nuclear Information System (INIS)

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

Clinicopathologic Features and Prognostic Implications in 72 Cases 
with Lung Adenosquamous Carcinoma

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Xi WU

2016-10-01

Full Text Available Background and objective Adenosquamous carcinoma (ASC is a rare subtype of lung cancer, it is mixed glandular and squamous cell carcinoma with a more aggressive behavior and poor prognosis than the other histologic subtypes. The aim of the study was to explore the clinicopathological characteristics and prognostic factors of ASC. Methods A total of 72 patients were enrolled. We investigated clinicalpathological features and prognostic factors retrospectively. Results The overall 72 ASC patients’ median age was 34.7 months, 5-year survival rate was 14.9%. The influence of tumor size, M stage, and N stage, gene mutation and surgery on the prognosis of patients show statistical significance. Conclusion ASC is characterized by both histologic aggressiveness and adverse prognosis. We suggest the comprehensive therapy based on surgery, and given small molecule tyrosine kinase inhibitors (TKIs treatment may prolong patients’ overall survival.

Spontaneous pneumothorax associated with lung cancer

International Nuclear Information System (INIS)

Sung, Dong Wook; Jung, Seung Hyae; Yoon, Yup; Lim, Jae Hoon; Cho, Kyu Soek; Yang, Moon Ho

1991-01-01

Spontaneous pneumothorax is a rare manifestation of lung cancer. Eight cases of pneumothorax found in 1648 patients with lung cancer from 1979-1990 are reported. Histopathologic types of cancer were adenocarcinoma in three cases, squamous cell carcinoma in two cases, bronchioloalveolar carcinoma in two cases, and metastatic renal cell carcinoma in one case. The primary tumor mass was not found even after thoracotomy in two cases. Spontaneous pneumothorax occurred on the ipsilateral side of the cancer. All the patients were more than 40 years old with a history of smoking 1-2 packs a day for 20 to 50 years, and had chronic lung diseases. The authors emphasize that bronchogenic carcinoma may be one of the causes of spontaneous pneumothorax in appropriate clinical settings

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

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Yingjen Jeffrey Wu

2009-02-01

Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma

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Hongliang REN

2016-04-01

Full Text Available Background and objective Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC and small cell lung carcinoma (SCLC. Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%, squamous cell carcinoma (SCC (20%-30%, and large cell carcinoma (10%. Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET/computed tomography (CT has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. Methods One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. Results The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022. There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM stage

Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

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Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

1984-02-01

Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

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

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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.

Experimental radioimmunoimaging of human lung small cell carcinoma xenograft H-69 by NCC-ST-433 monoclonal antibody

International Nuclear Information System (INIS)

Kubota, Tetsuro; Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Watanabe, Masahiko; Ishibiki, Kyuya; Abe, Osahiko

1989-01-01

NCC-ST-433 monoclonal antibody raised against human gastric carcinoma xenograft (St-4) was labeled with l25 I using enzymatic and Iodogen methods. While labeling efficiency of the antibody was more excellent by enzymatic method, specific radioactivity of the antibody labeled by Iodogen method was higher than that by enzymatic method. The labeled antibody was stable in vitro and in vivo, and the labeled NCC-ST-433 was specifically accumulated in NCC-ST-433 antigen positive human tumor cell lines in vitro. The specificity of 125 I-NCC-ST-433 in vivo was found to be more excellent when this antibody was labeled by Iodogen method and acutually excellent images of H-69, a human small cell lung carcioma, were obtained 5 days after injection of 7 μg of 125 I-NCC-ST-433 per mouse. This method seemed to be promising for imaging human lung small cell carcinoma. (author)

Small Cell Anaplastic Carcinoma of Primary Lung Tumor in a Miniature Schnauzer Dog

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J. M. Kim, H. J. Han, B. Ku, G. Kim, K. M. Shim1, S. S. Kang2 and S. H. Choi*

2011-04-01

Full Text Available A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully resected although adhered part of CVC could not be completely resected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma.

Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

International Nuclear Information System (INIS)

Kim, J.M.; Han, H.J.; Ku, B.; Kim, G.; Shim, K.M.; Kang, S.S.; Choi, S.H.

2011-01-01

A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

Curative radiotherapy in non-small cell carcinoma of the lung

International Nuclear Information System (INIS)

Talton, B.M.; Constable, W.C.; Kersh, C.R.

1990-01-01

Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques.Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk

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

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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

Radionuclide injury to the lung

International Nuclear Information System (INIS)

Dagle, G.E.; Sanders, C.L.

1984-01-01

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequently observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. 88 references

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.

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.

Relationship between tuberculous scar and carcinomas of the lung

International Nuclear Information System (INIS)

Richardson, S.; Hirsch, A.; Bickel, M.

1987-01-01

Results of a transversal case-control study are reported which shows that there is a statistically significant association between tuberculous scars and carcinoma of the lung. Accordingly the possibility of malignancy has to be kept in mind when radiological or scintigraphic scanning reveal the presence of lung scars. (orig.)

EVALUATION OF LYMPHATIC SPREAD, VISCERAL METASTASIS AND TUMORAL LOCAL INVASION IN ESOPHAGEAL CARCINOMAS.

Science.gov (United States)

Tustumi, Francisco; Kimura, Cintia Mayumi Sakurai; Takeda, Flavio Roberto; Sallum, Rubens Antônio Aissar; Ribeiro-Junior, Ulysses; Cecconello, Ivan

2016-01-01

Knowing esophageal tumors behavior in relationship to lymph node involvement, distant metastases and local tumor invasion is of paramount importance for the best esophageal tumors management. To describe lymph node involvement, distant metastases, and local tumor invasion in esophageal carcinoma, according to tumor topography and histology. A total of 444 patients with esophageal squamous cell carcinoma and 105 adenocarcinoma were retrospectively analyzed. They were divided into four groups: adenocarcinoma and squamous cell carcinoma in the three esophageal segments: cervical, middle, and distal. They were compared based on their CT scans at the time of the diagnosis. Nodal metastasis showed great relationship with of primary tumor site. Lymph nodes of hepatogastric, perigastric and peripancreatic ligaments were mainly affected in distal tumors. Periaortic, interaortocaval and portocaval nodes were more commonly found in distal squamous carcinoma; subcarinal, paratracheal and subaortic nodes in middle; neck chains were more affected in cervical squamous carcinoma. Adenocarcinoma had a higher frequency of peritoneal involvement (11.8%) and liver (24.5%) than squamous cell carcinoma. Considering the local tumor invasion, the more cranial neoplasia, more common squamous invasion of airways, reaching 64.7% in the incidence of cervical tumors. Middle esophageal tumors invade more often aorta (27.6%) and distal esophageal tumors, the pericardium and the right atrium (10.4%). Esophageal adenocarcinoma and squamous cell carcinoma in different topographies present peculiarities in lymph node involvement, distant metastasis and local tumor invasion. These differences must be taken into account in esophageal cancer patients' care. Conhecer o comportamento das neoplasias esofágicas em relação à disseminação linfonodal, distribuição de metástases e invasão local do tumor, pode auxiliar o manejo dos pacientes. Descrever o envolvimento linfonodal, disseminação metast

Vasculature analysis of patient derived tumor xenografts using species-specific PCR assays: evidence of tumor endothelial cells and atypical VEGFA-VEGFR1/2 signalings

International Nuclear Information System (INIS)

Bieche, Ivan; Marangoni, Elisabetta; Roman-Roman, Sergio; Decaudin, Didier; Dangles-Marie, Virginie; Vacher, Sophie; Vallerand, David; Richon, Sophie; Hatem, Rana; De Plater, Ludmilla; Dahmani, Ahmed; Némati, Fariba; Angevin, Eric

2014-01-01

Tumor endothelial transdifferentiation and VEGFR1/2 expression by cancer cells have been reported in glioblastoma but remain poorly documented for many other cancer types. To characterize vasculature of patient-derived tumor xenografts (PDXs), largely used in preclinical anti-angiogenic assays, we designed here species-specific real-time quantitative RT-PCR assays. Human and mouse PECAM1/CD31, ENG/CD105, FLT1/VEGFR1, KDR/VEGFR2 and VEGFA transcripts were analyzed in a large series of 150 PDXs established from 8 different tumor types (53 colorectal, 14 ovarian, 39 breast and 15 renal cell cancers, 6 small cell and 5 non small cell lung carcinomas, 13 cutaneous melanomas and 5 glioblastomas) and in two bevacizumab-treated non small cell lung carcinomas xenografts. As expected, mouse cell proportion in PDXs -evaluated by quantifying expression of the housekeeping gene TBP- correlated with all mouse endothelial markers and human VEGFA RNA levels. More interestingly, we observed human PECAM1/CD31 and ENG/CD105 expression in all tumor types, with higher rate in glioblastoma and renal cancer xenografts. Human VEGFR expression profile varied widely depending on tumor types with particularly high levels of human FLT1/VEGFR1 transcripts in colon cancers and non small cell lung carcinomas, and upper levels of human KDR/VEGFR2 transcripts in non small cell lung carcinomas. Bevacizumab treatment induced significant low expression of mouse Pecam1/Cd31, Eng/Cd105, Flt1/Vegfr1 and Kdr/Vefr2 while the human PECAM1/CD31 and VEGFA were upregulated. Taken together, our results strongly suggest existence of human tumor endothelial cells in all tumor types tested and of both stromal and tumoral autocrine VEGFA-VEGFR1/2 signalings. These findings should be considered when evaluating molecular mechanisms of preclinical response and resistance to tumor anti-angiogenic strategies

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.

Peritumoral edema associated with metastatic brain tumor

International Nuclear Information System (INIS)

Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

1992-01-01

Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

Inflammatory myofibroblastic tumor of the lung in pregnancy mimicking carcinoid tumor

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Venkata Nagarjuna Maturu

2016-01-01

Full Text Available Inflammatory myofibroblastic tumors (IMT are uncommon neoplasms of the lung in adults. They constitute less than 1% of all lung neoplasms and usually present as parenchymal masses. Diagnosis requires a high index of suspicion. They are characterized by spindle-shaped tumor cells (fibroblasts/myofibroblasts in a background of lymphoplasmacytic infiltrate. About 50% of the tumors harbor an ALK gene rearrangement. They have to be differentiated from inflammatory pseudotumors (IPT, which show increased number of IgG4 plasma cells on immunostaining and are negative for anaplastic lymphoma kinase (ALK protein. Herein, we present a case of a 28-year old female who presented with hemoptysis and was diagnosed with an IMT of lung in the first trimester of pregnancy. We have not only reviewed the occurrence of IMT during pregnancy but also discuss the management options for IMT during pregnancy.

Tumor budding in upper gastrointestinal carcinomas

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Viktor Hendrik Koelzer

2014-08-01

Full Text Available The basis of personalized medicine in oncology is the prediction of an individual’s risk of relapse and death from disease. The presence of tumor budding (TB at the tumor-host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: 1 Validation of prognostic scoring systems for tumor budding in large, multi-center studies 2 Consensus on the optimal assessment method 3 Inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study.

Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors.

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Eymin, Béatrice; Gazzeri, Sylvie; Brambilla, Christian; Brambilla, Elisabeth

2002-04-18

Pathways involving p53 and pRb tumor suppressor genes are frequently deregulated during lung carcinogenesis. Through its location at the interface of these pathways, Mdm2 can modulate the function of both p53 and pRb genes. We have examined here the pattern of expression of Mdm2 in a series of 192 human lung carcinomas of all histological types using both immunohistochemical and Western blot analyses and four distinct antibodies mapping different epitopes onto the Mdm2 protein. Using Immunohistochemistry (IHC), Mdm2 was overexpressed as compared to normal lung in 31% (60 out of 192) of all tumors analysed, whatever their histological types. Western blotting was performed on 28 out of the 192 tumoral samples. Overexpression of p85/90, p74/76 and p57 Mdm2 isoforms was detected in 18% (5 out of 28), 25% (7 out of 28) and 39% (11 out of 28) of the cases respectively. Overall, overexpression of at least one isoform was observed in 14 out of 28 (50%) lung tumors and concomittant overexpression of at least two isoforms in 7 out of 28 (25%) cases. A good concordance (82%) was observed between immunohistochemical and Western blot data. Interestingly, a highly significant inverse relationship was detected between p14(ARF) loss and Mdm2 overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P1 ratio was correlated with a high grade phenotype among NE tumors overexpressing Mdm2 (P=0.0021). Taken together, these data strongly suggest that p14(ARF)and Mdm2 act on common pathway(s) to regulate p53 and/or pRb-dependent or independent functions and that the Mdm2 : p14(ARF) ratio might act as a rheostat in modulating the activity of both proteins.

Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

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Ahmed M Ragab Shalaby

2016-01-01

Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3)

International Nuclear Information System (INIS)

Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-01-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF 1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free. (author)

Lifetime risk of urothelial carcinoma and lung cancer in the arseniasis-endemic area of Northeastern Taiwan

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Yang, Tse-Yen; Hsu, Ling-I.; Chen, Hui-Chi; Chiou, Hung-Yi; Hsueh, Yu-Mei; Wu, Meei-Maan; Chen, Chi-Ling; Wang, Yuan-Hung; Liao, Ya-Tang; Chen, Chien-Jen

2013-11-01

Arsenic in drinking water has been shown to increase the risk of urothelial carcinoma and lung cancer. However, the lifetime risk of developing urothelial carcinoma and lung cancer caused by exposure to arsenic in drinking water has not been reported. This study aimed to assess the lifetime risk of urothelial carcinoma and lung cancer caused by arsenic exposure from drinking water and cigarette smoking habit for residents living in the arseniasis-endemic area in Northeastern Taiwan. We recruited 8086 residents in 1991-1994 and monitored them for their newly developed types of cancers, identified by computerized linkage with the national cancer registry profile. There were 37 newly diagnosed urothelial carcinoma cases and 223 new lung cancer cases during the follow-up period (until 2007). The lifetime (35-85 years old) cumulative risk of developing urothelial carcinoma from an arsenic concentration in the drinking water of smoking was associated with an increased risk of urothelial carcinoma and lung cancer, showing the hazard ratio (95% confidence interval) of 2.48 (1.27-4.82) and 3.44 (2.00-5.90) after adjusting for the arsenic concentration in drinking water. After adjusting for cigarette smoking, the hazard ratio (95% confidence interval) of developing urothelial carcinoma caused by the arsenic concentration in drinking water of smoking. It is suggested that people who have had a high exposure to arsenic in drinking water should stop smoking cigarettes to lower their lifetime risk of urothelial carcinoma and lung cancer.

Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

DEFF Research Database (Denmark)

Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

1986-01-01

A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different...... sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow...

A contribution to radiotherapy of the larger-celled bronchial carcinoma

International Nuclear Information System (INIS)

Zoubie, I.

1982-01-01

This work consists of a retrospective definition of disease courses of 859 patients with lung tumors and the definition of the survival curves in their dependence on histology, radiation dose and sex. With 721 larger-celled bronchial carcinomas the ratio of men to women was 12:1. The age peak lay between 60 and 70 years. The one/five year survival rate of all included larger-celled bronchial carcinomas (n=701) was, independent from the therapy form, 35.7, resp. 4.78%. The one year/five year survival rates were for the squamous epithelia 31.08/0.58%, for the undifferentiated carcinomas 25.34/3.41%, and for the lung tumors without histology 35.4/5.14%. Lobectomized patients with squamous epithelium carcinoma had in comparison to pneumonectomized patients a clearly higher survival chance. A clearly sex-dependent predisposition for a certain type of carcinoma was not present. (TRV) [de

of lung metastases carcinoma of the cervix Surgical excision from ...

African Journals Online (AJOL)

of lung metastases carcinoma of the cervix. Surgical excision from squamous. A report of 2 cases. N. G. DE MOOR, A. V. BERRY, M. M. NISSENBAUM. These2casereportsservetoemphasizetwoimpor- tant points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; ...

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

International Nuclear Information System (INIS)

Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

2007-01-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

International Nuclear Information System (INIS)

Yasumoto, Kosei; Hanagiri, Takeshi; Takenoyama, Mitsuhiro

2009-01-01

Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

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Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

2016-03-01

Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

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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.

Primary bronchial carcinoma or pulmonary metastases

International Nuclear Information System (INIS)

Hasse, J.

1987-01-01

Operative treatment offers the best chance for long term survival in lung cancer of early stage. In the same way surgery may be the most efficient treatment of lung metastases from tumors of extrapulmonary site. The preoperative investigations have to prove that in case of lung cancer this is restricted to one hemithorax and in lung metastases that these are restricted to the lungs exclusively. They also have to prove that the lung function allows adequate resection. This is mainly lobectomy and pneumonectomy, sometimes sleeve resection and rarely segmentectomy for primary lung cancers. Resection of metastases preferably is by wedge excision or enucleation. In bilateral lesions median sternotomy is the favoured approach to both lungs in a single session. Long term results in primary lung cancer depend on the tumor stage. As a rule of thumb by each step of tumor stage the 5-year-survival rate is cut to half. In regard to histology small cell undifferentiated carcinomas are considered surgical indications only in the very early stage and need to be treated by adjuvant chemotherapy. The operative mortality is correlated to the extent of resection and by average is higher for primary carcinoma of the lung because of the usually higher age level and additional pulmonary damage. Patients operated for pulmonary metastases, however, are in lower age range and due to less functional risks, the operative mortality in most series is between 0 and 3%. Early detection of lung cancer, i.e., immediate and expert exploration of suspicious X-ray findings or respiratory symptoms particularly in smokers and with asbestos exposed individuals will contribute to an increasing efficacy of surgical treatment. (orig.) [de

Laser photoradiation therapy in the treatment of malignant tumors

International Nuclear Information System (INIS)

Tomio, L.; Corti, L.; Polico, C.

1987-01-01

Photoradiation theraphy or, as more recently defined, photodynamic theraphy (PDT) has been effective in the treatment of several kinds of cancers, above all the skin, lung, esophagus and bladder. It is based on the preferential retention by tumor and photosensitizing properties of certains porphyrins.It has been initiated to investigate this technique experimentally in 1978 and clinically in september 1982, with report of the initial results in 38 patients in 1985. In this paper the more recent experience of PDT in 18 patients affected by different tumors and treated with a new double argon-dye laser system is described. These tumors included 8 carcinomas of the esophagus, 5 basal cell skin cancers, 2 carcinomas of the lung, 2 squamous cell carcinomas of the oral cavity and 1 early gastric cancer. Clinical results and technical problems of PDT are discussed

Validations of SCT Methylation as a Hallmark Biomarker for Lung Cancers

Science.gov (United States)

Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-01-01

Background The human secretin (SCT) gene encodes secretin, a hormone with limited tissue distribution. Analysis of The Cancer Genome Atlas (TCGA) 450K methylation array data indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential cancer biomarker for lung cancer. Methods We analyzed TCGA data, and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP) assays. Results The analyses of TCGA 450K data of 801 samples showed that SCT hypermethylation has an area under curve (AUC) value >0.98 to distinguish lung adenocarcinomas or squamous cell carcinomas from non-malignant lung. We confirmed the highly discriminative SCT methylation by bisulfite sequencing of lung cancer cell lines and normal blood cells. By applying qMSP, we found that SCT hypermethylation was frequently detected in all major subtypes of malignant NSCLC (AUC=0.92, n=108) and SCLC cancers (AUC=0.93, n=40) but less frequently present in lung carcinoids (AUC=0.54, n=20). SCT hypermethylation appeared in lung carcinoma in situ samples during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450K data showed that SCT hypermethylation is highly discriminative in most types of other malignant tumors but less frequently present in low-grade malignant tumors. The only normal tissue with high methylation was the placenta. Conclusions Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, and less frequently present in low-grade malignant tumors including lung carcinoids, and appears at the carcinoma in situ stage. PMID:26725182

Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

International Nuclear Information System (INIS)

Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E; Ditzel, Henrik J

2013-01-01

The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC. Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis. GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations. Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial

Use of imaging in assessing lung carcinoma

Energy Technology Data Exchange (ETDEWEB)

Webb, W R [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

Staging of bronchogenic carcinoma, invasive primary tumors, tracheal or carinal involvement, chest wall invasion, mediastinal invasion, malignant pleural effusion, lymph node metastases, mediastinal nodes, hilar masses briefly discussed (47 refs.).

Use of imaging in assessing lung carcinoma

International Nuclear Information System (INIS)

Webb, W.R.

1995-01-01

Staging of bronchogenic carcinoma, invasive primary tumors, tracheal or carinal involvement, chest wall invasion, mediastinal invasion, malignant pleural effusion, lymph node metastases, mediastinal nodes, hilar masses briefly discussed (47 refs.)

Accumulation of 99Tcm MDP in lung cancer of 84 patients

International Nuclear Information System (INIS)

Yang, Y.S.F.; Zeng, Z.J.; Shao, S.J.L.; Shi, S.M.P.; Zheng, Z.Z.C.

2002-01-01

Objective: To analyze the clinic mechanisms of technetium-99m-methyl-diphosphate ( 99 Tc m -MDP) uptake in lung cancer. Methods: 84 patients (63 men, 21 women; mean age 61.56 years) with lung cancer and no effusion underwent bone scan. Of 84, there were primary lung cancer in 63 cases and metastatic lung cancer in 21 cases. 28 adenocarcinomas, 32 squamous carcinomas, 9 adenosquamous carcinomas, 9 non-classified non-small cell lung cancers, 6 small cell lung carcinomas. Final diagnoses were established by histology in all patients. The bone scan was performed 3-8h after i.v. injection of 1295MBq 99 Tc m -MDP. The whole body scan was performed using a SPET camera (MULTISPECT2, Siemans) and the scan speed was 11cm/min. Tracer uptake was visual and semi-quantitative analyzed for each patient. The expression of 99 Tc m -MDP uptake in lung was determined the intensity and then took semi-quantitative analysis of 99 Tc m -MDP uptake, regions of interest (RIOs) placed on the lesions encompassed all pixels and horizontal copied to normal lung in anterior and posterior view, and the average count ratio (tumor to normal lung T/N) in each ROI was calculated. We analyzed the ratio by computing the standardized uptake measures (SUMs) to determine the tumor-positive value (T/N) greater than or equal to 1.2. All 99 Tc m -MDP images were carefully compared with their contemporaneous chest roentgenograms, CT and histopathology studies. Results: For statistics analysis of the 99 Tc m -MDP uptake in lung cancer, the men were 81% in 63 cases, women 19% in 21; the age of less than or equal to fifty years old is 12% in 10; poorly differentiated carcinoma was 48.8% in 41, med-differentiated carcinoma was 39.3% in 33 and differentiated was 11.9% in 10;the patients of chemotherapy were 32.1% in 27; the metastatic lymph nodules were 51.2% in 43; the diameter of tumor with larger than 5 cm was 72.4% in 60;pleura involvement was 83.7% in 36; necrosis was 76.8% in 33; abnormality of enzyme (GPT

Dynamic volume perfusion CT in patients with lung cancer: Baseline perfusion characteristics of different histological subtypes

International Nuclear Information System (INIS)

Shi, Jingyun; Schmid-Bindert, Gerald; Fink, Christian; Sudarski, Sonja; Apfaltrer, Paul; Pilz, Lothar R.; Liu, Bo; Haberland, Ulrike; Klotz, Ernst

2013-01-01

Objective: To evaluate dynamic volume perfusion CT (dVPCT) tumor baseline characteristics of three different subtypes of lung cancer in untreated patients. Materials and methods: 173 consecutive patients (131 men, 42 women; mean age 61 ± 10 years) with newly diagnosed lung cancer underwent dVPCT prior to biopsy. Tumor permeability, blood flow (BF), blood volume (BV) and mean transit time (MTT) were quantitatively assessed as well as tumor diameter and volume. Tumor subtypes were histologically determined and compared concerning their dVPCT results. dVPCT results were correlated to tumor diameter and volume. Results: Histology revealed adenocarcinoma in 88, squamous cell carcinoma in 54 and small cell lung cancer (SCLC) in 31 patients. Tumor permeability was significantly differing between adenocarcinoma, squamous cell carcinoma and SCLC (all p < 0.05). Tumor BF and BV were higher in adenocarcinomathan in SCLC (p = 0.001 and p = 0.0002 respectively). BV was also higher in squamous cell carcinoma compared to SCLC (p = 0.01). MTT was not differing between tumor subtypes. Regarding all tumors, tumor diameter did not correlate with any of the dVPCT parameters, whereas tumor volume was negatively associated with permeability, BF and BV (r = −0.22, −0.24, −0.24, all p < 0.05). In squamous cell carcinoma, tumor diameter und volume correlated with BV (r = 0.53 and r = −0.40, all p < 0.05). In SCLC, tumor diameter und volume correlated with MTT (r = 0.46 and r = 0.39, all p < 0.05). In adenocarcinoma, no association between morphological and functional tumor characteristics was observed. Conclusions: dVPCT parameters are only partially related to tumor diameter and volume and are significantly differing between lung cancer subtypes

Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

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Akira Suzuki

2012-01-01

Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

High resolution CT for localization of early hilar lung carcinoma

International Nuclear Information System (INIS)

Minami, Yuko; Ishikawa, Shigemi; Saida, Yukihisa; Kajitani, Motomasa; Yamamoto, Tatsuo; Sato, Yukio; Onizuka, Masataka; Sakakibara, Yuzuru; Noguchi, Masayuki

2002-01-01

The purpose of this study was to analyse the usefulness of high resolution CT (HRCT) for the diagnosis and localization of roentgenographically occult lung cancer. HRCT was performed prospectively on chest X-ray negative patients with bloody sputum or suspicious or positive cells on sputum cytology between 1998 and 2000. After the HRCT scan, white light bronchoscopy and autofluorescence bronchoscopy were performed. HRCT depicted 19 hilar bronchial lesions in 13 cases out of 19 patients, of which 9 lesions were confirmed by white light broncoscope. Of 8 hilar squamous cell carcinomas diagnosed in this study, 7 lesions (87.5%) were depicted by HRCT. One CT-negative case (12.5%) was an in situ carcinoma in left B 1+2 . Four out of 20 lesions which showed bronchoscopic abnormality, could not be depicted by HRCT. HRCT could prospectively detect 80% of the bronchoscopic abnormalities and 87.5% of the hilar squamous cell carcinomas of the tracheobronchial lesions of the lung. Therefore, HRCT can be an effective supplemental means for screening for hilar squamous cell carcinoma. (author)

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

International Nuclear Information System (INIS)

Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

2010-01-01

To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.

Science.gov (United States)

Yurugi, Yohei; Wakahara, Makoto; Matsuoka, Yuki; Sakabe, Tomohiko; Kubouchi, Yasuaki; Haruki, Tomohiro; Nosaka, Kanae; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Shiomi, Tatsushi; Nakamura, Hiroshige; Umekita, Yoshihisa

2017-01-01

Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

International Nuclear Information System (INIS)

Kato, H.; Torigoe, T.

1977-01-01

A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

Diet and lung cancer in California Seventh-day Adventists.

Science.gov (United States)

Fraser, G E; Beeson, W L; Phillips, R L

1991-04-01

The Adventist Health Study, a cohort study of 34,198 California Seventh-day Adventists, identified 61 cases of new primary lung cancer over 6 years of follow-up (1977-1982). The population studied was unique in that only 4% admitted to current cigarette smoking and about half were lacto-ovovegetarians. A total of 36% of the lung tumors were adenocarcinomas, and 19% were squamous cell carcinomas. The expected associations with cigarette smoking were noted for Kreyberg group I tumors (squamous cell, large cell, and small cell carcinoma; relative risk (RR) = 53.2 for current smokers and 7.07 for past smokers), but much lesser associations were noted for Kreyberg group II tumors (adenocarcinoma and bronchoalveolar carcinoma; RR = 1.99 for current smokers and 1.59 for past smokers). In this study, fruit consumption was the dietary constituent that showed a strong, statistically significant protective association with lung cancer that was independent of smoking (fruit consumption less than 3 times/week, RR = 1.0; 3-7 times/week, RR = 0.30; greater than or equal to 2 times/day, RR = 0.26). This association was somewhat stronger for Kreyberg group II tumors, but similar trends were also noted for Kreyberg group I tumors. Confounding with smoking seems unlikely in a population with very few current smokers and where both stratification and Cox modeling methods of analysis led to similar conclusions.

Dependence of radiotherapeutic results on tumor size in patients with cervix uteri carcinoma

International Nuclear Information System (INIS)

Gabelov, A.A.; Zharinov, G.M.

1981-01-01

A method is suggested that permits specifying the primary tumor size on the basis of clinical examination of patients with cervix uteri carcinoma. The values of tumor size have been correlated with long-term results of concomitant radiotherapy in 1358 patients with cervix uteri carcinoma. The data obtained have shown that the primary tumor size is a factor that determines to a large extent radiotherapeutic results in patients with cervix uteri carcinoma. The specification of tumor size values makes it possible to considerably lessen prognostic uncertainty of present-day staging classifications. The structure of radiotherapeutic failures also turned out to be closely associated with the primary tumor size

Intratumoral Immunization by p19Arf and Interferon-β Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma

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João Paulo Portela Catani

2016-12-01

Full Text Available Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-β (IFNβ in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFNβ significantly induced markers of immunogenic cell death. In situ gene therapy with IFNβ, either alone or in combination with p19Arf, could retard tumor progression, but only the combined treatment was associated with a protective immune response. Specifically in the case of combined intratumoral gene transfer, we identified 167 differentially expressed genes when using microarray to evaluate tumors that were treated in vivo and confirmed the activation of CCL3, CXCL3, IL1α, IL1β, CD274, and OSM, involved in immune response and chemotaxis. Histologic evaluation revealed significant tumor infiltration by neutrophils, whereas functional depletion of granulocytes ablated the antitumor effect of our approach. The association of in situ gene therapy with cisplatin resulted in synergistic elimination of tumor progression. In all, in situ gene transfer with p19Arf and IFNβ acts as an immunotherapy involving recruitment of neutrophils, a desirable but previously untested outcome, and this approach may be allied with chemotherapy, thus providing significant antitumor activity and warranting further development for the treatment of lung carcinoma.

Lung tumor segmentation in PET images using graph cuts.

Science.gov (United States)

Ballangan, Cherry; Wang, Xiuying; Fulham, Michael; Eberl, Stefan; Feng, David Dagan

2013-03-01

The aim of segmentation of tumor regions in positron emission tomography (PET) is to provide more accurate measurements of tumor size and extension into adjacent structures, than is possible with visual assessment alone and hence improve patient management decisions. We propose a segmentation energy function for the graph cuts technique to improve lung tumor segmentation with PET. Our segmentation energy is based on an analysis of the tumor voxels in PET images combined with a standardized uptake value (SUV) cost function and a monotonic downhill SUV feature. The monotonic downhill feature avoids segmentation leakage into surrounding tissues with similar or higher PET tracer uptake than the tumor and the SUV cost function improves the boundary definition and also addresses situations where the lung tumor is heterogeneous. We evaluated the method in 42 clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our method improves segmentation and performs better than region growing approaches, the watershed technique, fuzzy-c-means, region-based active contour and tumor customized downhill. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

DEFF Research Database (Denmark)

Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu

2011-01-01

Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies we...

Definitive radiation therapy for clinical stage N0-N1 epidermoid carcinoma of the lung

International Nuclear Information System (INIS)

Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro; Yamakawa, Michitaka; Nakayama, Yuko; Katano, Susumu; Furuta, Masaya; Niibe, Hideo

1993-01-01

From 1976 through 1989, 94 patients with epidermoid carcinoma of the lung without mediastinal nodal involvement were treated with definitive radiation therapy (RT) at Gunma University Hospital. All patients were treated with 10 MV X-rays and the mediastinum was treated in 86% of the patients. The total dose ranged from 60 Gy to 80 Gy with once-daily conventional fractionation. The actuarial two and five-year survival rates of the entire group were 44% and 22%, respectively, with a median survival time (MST) of 17 months. Patients with a performance status of 0-1 lived longer than those with a status of 2 or more (MST 22.5 vs. 12 months). The survival of 60 patients with T2 tumors was better than that of 24 patients with T3 tumors (MST 19 vs. 13.5 months). Forty-seven patients with tumors less than 5 cm in diameter had a two-year progression rate of 25%, in comparison with 39% for 47 patients with tumors greater than 5 cm. The survival difference between these two groups was statistically significant (p<0.01). Patients given a total dose of 80 Gy or over had only 20% local progression at the time of the last follow-up, but they had a lower long-term survival rate than those given a total dose of 60-74 Gy because of the development of pulmonary insufficiency after high-dose irradiation. There was no relapse in the field given 40 Gy or more to the mediastinum for prophylaxis in the patients with no evidence of primary progression. The actuarial five-year survival rates for the patients given 40 Gy or more to the mediastinum, and for the patients given less than 40 Gy were 32% and 9%, respectively. These was a statistically significant difference between these two survival curves, (p<0.05). Differences in survival did not depend on age, sex, or location of the primary tumor. These results should provide support for definitive RT to manage patients with medically inoperable or unresectable epidermoid carcinoma of the lung without mediastinal nodal involvement. (author)

Long-term survival in inoperable squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Ono, Ryosuke; Egawa, Sunao

1988-01-01

Radiotherapy is the first treatment of choice in cases of inoperable lung cancer. This paper reported the indications and limitations of radiotherapy for squamous cell carcinoma of the lung, based on the results of long-term survivors among non-resected squamous cell carcinoma. Materials consisted of 372 cases of squamous cell carcinoma of the lung treated with radiotherapy at the National Cancer Center Hospital between May 1962 and December 1980. Histopathological diagnosis was confirmed by biopsy in all cases. Among the 372 cases, 8 survived more than 5 years. Analyzing these 8 cases according to the TNM classification of the UICC, 7 were stage I, 1 was stage II, and there were no long-term survivors with stage III or IV. Of the 8 cases only one is alive. Analyzing 7 the fatal cases, 2 succumbed due to hepatic or brain metatasis following local recurrence and one had double primary cancer of the pancreas. The remaining 4 cases did not show recurrence or metastasis and succumbed due to pneumonia or myocardial infarct. (author)

Percutaneous radiofrequency ablation of lung tumors in a large animal model.

Science.gov (United States)

Ahrar, Kamran; Price, Roger E; Wallace, Michael J; Madoff, David C; Gupta, Sanjay; Morello, Frank A; Wright, Kenneth C

2003-08-01

Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.

Tumor scanning with /sup 57/Co-bleomycin

Energy Technology Data Exchange (ETDEWEB)

Nakano, S; Hasegawa, Y; Matsuda, Minoru; Ho, T; Doi, O [Osaka Prefectural Center for Adult Diseases (Japan)

1975-06-01

The clinical application of /sup 57/Co-bleomycin as a tumor scanning radiopharmaceutical was firstly reported by Nouel and Maeda respectively. The authors conducted studies on the diagnostic significance of this tumor scanning agent and presented the results obtained in 40 patients with malignant and non malignant lesions. Six hours and 24 hours after the injection of 500 ..mu..Ci of /sup 57/Co-bleomycin, scintigrams were taken with a 3-inch scintiscanner. Positive scans were found in 20 out of 36 patients with various malignant tumors. Of 20 patients with lung cancer, positive scans were obtained in 17 cases (85%) and of 6 with breast cancer, 3 cases showed positive scans. False negative scans were obtained in another 10 cases of malignant tumors (3 cases of thyroid carcinoma, 4 cases of hepatoma, and 1 case each of gastric carcinoma, peritoneal carcinomatosis, and reticulum cell sarcoma). Of 4 patients with non malignant disease, one case of pulmonary tuberculosis showed a positive scan. In 8 cases of lung cancer and 6 of breast cancer, the relationship between the size of the excised tumor and the scintigram findings was studied. The smallest tumors detected by scintigram were 2 cm in lung cancer and 3.2 cm in breast cancer.

Human papillomavirus-16 presence and physical status in lung carcinomas from Asia

Directory of Open Access Journals (Sweden)

Morewaya Jacob

2010-11-01

Full Text Available Abstract Background Although human papillomavirus (HPV genome has been detected in lung cancer, its prevalence is highly variable around the world. Higher frequencies have been reported in far-east Asian countries, when compared with European countries. The present study analysed the HPV-16 presence in 60 lung carcinomas from the Asian countries China, Pakistan and Papua New Guinea. Results HPV-16 was present in 8/59 (13% samples. According to histological type, HPV-16 was detected in 8/18 (44% squamous cell carcinomas (SQCs, which were mainly from Pakistan; 0/38 (0% adenocarcinomas (ACs, which were mainly from China; and in 0/4 (0% small cell carcinomas (SCLCs. The observed histological difference was statistically significant (p Conclusion These results support the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our results show a frequent HPV-16 integration in SQCs, although the low viral load casts doubt respect a direct etiological role of HPV in lung carcinomas from Asia. Additional HPV-16 characterization is necessary to establish a direct or indirect etiological role of HPV in this malignancy.

Tumor cell surface proteins

International Nuclear Information System (INIS)

Kennel, S.J.; Braslawsky, G.R.; Flynn, K.; Foote, L.J.; Friedman, E.; Hotchkiss, J.A.; Huang, A.H.L.; Lankford, P.K.

1982-01-01

Cell surface proteins mediate interaction between cells and their environment. Unique tumor cell surface proteins are being identified and quantified in several tumor systems to address the following questions: (i) how do tumor-specific proteins arise during cell transformation; (ii) can these proteins be used as markers of tumor cell distribution in vivo; (iii) can cytotoxic drugs be targeted specifically to tumor cells using antibody; and (iv) can solid state radioimmunoassay of these proteins provide a means to quantify transformation frequencies. A tumor surface protein of 180,000 M/sub r/ (TSP-180) has been identified on cells of several lung carcinomas of BALB/c mice. TSP-180 was not detected on normal lung tissue, embryonic tissue, or other epithelial or sarcoma tumors, but it was found on lung carcinomas of other strains of mice. Considerable amino acid sequence homology exists among TSP-180's from several cell sources, indicating that TSP-180 synthesis is directed by normal cellular genes although it is not expressed in normal cells. The regulation of synthesis of TSP-180 and its relationship to normal cell surface proteins are being studied. Monoclonal antibodies (MoAb) to TSP-180 have been developed. The antibodies have been used in immunoaffinity chromatography to isolate TSP-180 from tumor cell sources. This purified tumor antigen was used to immunize rats. Antibody produced by these animals reacted at different sites (epitopes) on the TSP-180 molecule than did the original MoAb. These sera and MoAb from these animals are being used to identify normal cell components related to the TSP-180 molecule

CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

International Nuclear Information System (INIS)

Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

1994-01-01

The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

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.

Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

2013-01-01

Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells

Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

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Dudás, József, E-mail: jozsef.dudas@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullár, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Romani, Angela, E-mail: angela.romani@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pritz, Christian, E-mail: christian.pritz@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Hans Schartinger, Volker, E-mail: volker.schartinger@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Mathias Sprinzl, Georg, E-mail: georg.sprinzl@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: herbert.riechelmann@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

2013-04-01

Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

Metastatic giant basal cell carcinoma: a case report.

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Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

2016-01-01

Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

Clear cell carcinoma of the ovary mimicking struma ovarii and carcinoid tumor.

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Alduaij, Ahmad; Quddus, M Ruhul

2011-04-01

Clear cell carcinomas are considered as high-grade tumor often with poor prognosis. We describe 2 cases of clear cell carcinomas of the ovary mimicking benign or less aggressive tumors encountered in the female genital track. The first case is mimicking a benign monodermal teratoma, the so-called struma ovarii, and the second mimicking a carcinoid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

Carcinoma mucoepidermóide Mucoepidermoid carcinoma

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CRISTIANO FEIJÓ ANDRADE

2002-11-01

Full Text Available O carcinoma mucoepidermóide é uma neoplasia infreqüente da árvore traqueobrônquica e de etiologia ainda indeterminada. Sua localização endobrônquica preferencial freqüentemente causa sintomas respiratórios obstrutivos e pneumopatias de resolução lenta. Normalmente, são tumores de crescimento lento, mas que podem apresentar comportamento agressivo, com invasão local e metástases para linfonodos, dependendo das suas características histopatológicas. O tratamento de eleição é o cirúrgico, com ressecção completa, seja através de lobectomia ou broncotomia e broncoplastia. O prognóstico dependerá do grau de diferenciação celular desses tumores. Relata-se um caso dessa rara neoplasia descrevendo suas características clínicas, radiológicas e o tratamento cirúrgico.Mucoepidermoid carcinoma is an uncommon neoplasm of the tracheobronchial tree, of unknown etiology. Its preferred endobronchial location often results in respiratory symptoms such as obstruction of the airways and lung diseases of slow recovery. They usually are slow growing tumors although they may present an aggressive behavior with local invasion and lymph node metastases depending on their histopathologic characteristics. The mainstay therapy is complete surgical resection either by means of lobectomy or by lung sparing procedures such as bronchotomy and bronchoplasty. Prognosis depends upon the degree of cellular differentiation of the tumors. The authors report a case of this rare neoplasia and describe the clinical and radiographic characteristics, and the surgical treatment.

Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.

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Satoshi Takagi

Full Text Available The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis. Interestingly, the MS-1 monoclonal antibody attenuated the growth of Aggrus-positive tumors in vivo. Moreover, the humanized chimeric MS-1 antibody, ChMS-1, also exhibited strong antitumor activity against Aggrus-positive lung squamous cell carcinoma xenografted into NOD-SCID mice compromising antibody-dependent cellular cytotoxic and complement-dependent cytotoxic activities. Because Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth of the lung squamous cell carcinoma in vivo, Aggrus may be involved in not only tumor metastasis but also tumor growth by promoting platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Our results indicate that molecular target drugs inhibiting specific platelet-tumor interactions can be developed as antitumor drugs that suppress both metastasis and proliferation of tumors such as lung squamous cell carcinoma.

A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

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Orre Lotta

2010-02-01

Full Text Available Abstract Background In-depth proteomics analyses of tumors are frequently biased by the presence of blood components and stromal contamination, which leads to large experimental variation and decreases the proteome coverage. We have established a reproducible method to prepare freshly collected lung tumors for proteomics analysis, aiming at tumor cell enrichment and reduction of plasma protein contamination. We obtained enriched tumor-cell suspensions (ETS from six lung cancer cases (two adenocarcinomas, two squamous-cell carcinomas, two large-cell carcinomas and from two normal lung samples. The cell content of resulting ETS was evaluated with immunocytological stainings and compared with the histologic pattern of the original specimens. By means of a quantitative mass spectrometry-based method we evaluated the reproducibility of the sample preparation protocol and we assessed the proteome coverage by comparing lysates from ETS samples with the direct lysate of corresponding fresh-frozen samples. Results Cytological analyses on cytospin specimens showed that the percentage of tumoral cells in the ETS samples ranged from 20% to 70%. In the normal lung samples the percentage of epithelial cells was less then 10%. The reproducibility of the sample preparation protocol was very good, with coefficient of variation at the peptide level and at the protein level of 13% and 7%, respectively. Proteomics analysis led to the identification of a significantly higher number of proteins in the ETS samples than in the FF samples (244 vs 109, respectively. Albumin and hemoglobin were among the top 5 most abundant proteins identified in the FF samples, showing a high contamination with blood and plasma proteins, whereas ubiquitin and the mitochondrial ATP synthase 5A1 where among the top 5 most abundant proteins in the ETS samples. Conclusion The method is feasible and reproducible. We could obtain a fair enrichment of cells but the major benefit of the method

Sarcoma pleomórfico primário do pulmão Primary pleomorphic sarcoma of the lung

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Marcus da Matta Abreu

2008-07-01

Full Text Available A classificação recente da Organização Mundial da Saúde (OMS para os tumores pulmonares unificou o heterogéneo grupo do carcinoma de não pequenas células (CPNPC, que engloba os sarcomas e os tumores com componentes sarcomatosos, sob a denominação “carcinoma com elementos pleomórficos, sarcomatóides ou sarcomatosos”. Este grupo inclui diferentes entidades, como o carcinoma pleomórfico (CP, o carcinoma de células fusiformes (CCF, carcinoma de células gigantes (CCG, os carcinossarcomas (CS e o blastoma pulmonar (BP. De uma forma geral, estes tumores são raros e representam 0,1% a 0,4% de todas as neoplasias pulmonares. Ocorrem mais comummente em homens fumadores, com alta carga tabágica, e acomete-os em torno dos 60 anos e comummente tem evolução clínica muito agressiva. Os autores relatam o caso de um doente portador de sarcoma pleomórfico primário pulmonar e revêem a literatura sobre o assunto.The World Health Organization (WHO classification of lung cancers ranks the heterogeneous nonsmall cell lung cancer (N-SCLC group, encompassing sarcoma or sarcoma-containing tumours under one heading: “carcinomas with pleomorphic, sarcomatoid or sarcomatous elements”. This group contains entities such as pleomorphic carcinoma (PC, spindle cell carcinoma (SCC, giant cell carcinoma (GCC, carcinosarcoma (CS and pulmonary blastoma (PB. These tumors are rare overall, making up approx. 0.1-0.4% of all lung malignancies. They are more commonly found in males who are heavy smokers, diagnosed at the age of 60 on average and follow an aggressive clinical course. The authors describe the case of a male patient with primary pleomorphic lung sarcoma and also include a review of the literature.

Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

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Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

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Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Impact of urothelial carcinoma with divergent differentiation on tumor stage

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S Chalise

2016-03-01

Full Text Available Background: Urinary bladder cancer is classified as urothelial or non-urothelial. Ninenty percent of bladder cancer are urothelial and has propensity for divergent differentiation. Squamous differentiation is associated with unfavourable prognostic features. The aim of this study is to determine the significance of urothelial carcinoma with divergent differentiation in relation to tumor stage and lymphovascular as well as perineural invasion in radical cystectomy and partial cystectomy specimen.Materials and methods: This prospective study was done among 51 patients who underwent radical cystectomy or partial cystectomy at Bhaktapur Cancer Hospital from 1st August 2013 to 31st December 2015. Received specimen was grossed following standard protocol and histopathological evaluation was done in relation to tumor type, depth of invasion, Lymphovascular and perineural invasion.Results: Pure urothelial carcinoma comprises 47.1% of cases. Among the divergent differentiation, urothelial carcinoma with squamous differentiation was the commonest one (39.2% followed by glandular differentiation (5.9%, sarcomatoid differentiation (3.9%, clear cell variant (2.0% and squamous along with sarcomatoid variant (2.0%. Statistical significant correlation was found between urothelial carcinoma with divergent differentiation and tumor stage (p<0.012. Statistically significant correlation was also found between urothelial carcinoma with divergent differentiation and lymphovascular invasion (p=0.012 as well as perineural invasion (p=0.037.Conclusion:  Most common divergent differentiation was squamous differentiation. Urothelial carcinoma with divergent differentiation was associated with higher stage and lymphovascular as well as perineural invasion. So it is mandatory to search for the divergent differentiation in urothelial carcinoma as this may be associated with unfavourable prognosis.

Survival prognostic factors for patients with synchronous brain oligometastatic non-small-cell lung carcinoma receiving local therapy

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Bai H

2016-07-01

Full Text Available Hao Bai,1,* Jianlin Xu,1,* Haitang Yang,2,* Bo Jin,1 Yuqing Lou,1 Dan Wu,3 Baohui Han1 1Department of Pulmonary, 2Department of Pathology, 3Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Introduction: Clinical evidence for patients with synchronous brain oligometastatic non-small-cell lung carcinoma is limited. We aimed to summarize the clinical data of these patients to explore the survival prognostic factors for this population. Methods: From September 1995 to July 2011, patients with 1–3 synchronous brain oligometastases, who were treated with stereotactic radiosurgery (SRS or surgical resection as the primary treatment, were identified at Shanghai Chest Hospital.Results: A total of 76 patients (22 patients underwent brain surgery as primary treatment and 54 patients received SRS were available for survival analysis. The overall survival (OS for patients treated with SRS and brain surgery as the primary treatment were 12.6 months (95% confidence interval [CI] 10.3–14.9 and 16.4 months (95% CI 8.8–24.1, respectively (adjusted hazard ratio =0.59, 95% CI 0.33–1.07, P=0.08. Among 76 patients treated with SRS or brain surgery, 21 patients who underwent primary tumor resection did not experience a significantly improved OS (16.4 months, 95% CI 9.6–23.2, compared with those who did not undergo resection (11.9 months, 95% CI 9.7–14.0; adjusted hazard ratio =0.81, 95% CI 0.46–1.44, P=0.46. Factors associated with survival benefits included stage I–II of primary lung tumor and solitary brain metastasis. Conclusion: There was no significant difference in OS for patients with synchronous brain oligometastasis receiving SRS or surgical resection. Among this population, the number of brain metastases and stage of primary lung disease were the factors associated with a survival benefit. Keywords: non-small-cell lung carcinoma

meta-analysis of Serum Tumor Markers in Lung Cancer

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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.

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

International Nuclear Information System (INIS)

Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo

2013-01-01

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.

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

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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.

SU-G-JeP1-06: Correlation of Lung Tumor Motion with Tumor Location Using Electromagnetic Tracking

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Muccigrosso, D; Maughan, N; Parikh, P [Washington University School of Medicine, Saint Louis, MO (United States); Schultejans, H; Bera, R [Lindbergh High School, St. Louis, MO (United States)

2016-06-15

Purpose: It is well known that lung tumors move with respiration. However, most measurements of lung tumor motion have studied long treatment times with intermittent imaging; those populations may not necessarily represent conventional LINAC patients. We summarized the correlation between tumor motion and location in a multi-institutional trial with electromagnetic tracking, and identified the patient cohort that would most benefit from respiratory gating. Methods: Continuous electromagnetic transponder data (Varian Medical, Seattle, WA) of lung tumor motion was collected from 14 patients (214 total fractions) across 3 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath-holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. The average three-dimensional displacement from the breathing cycle’s end-expiratory to end-inhalation phases (peak-to-peak distance) of the transponders’ isocenter was calculated for each patient’s treatment. A weighted average of each isocenter was used to assess the effects of location on motion. A total of 14 patients were included in this analysis, grouped by their transponders’ location in the lung: upper, medial, and lower. Results: 8 patients had transponders in the upper lung, and 3 patients each in the medial lobe and lower lung. The weighted average ± standard deviation of all peak-to-peak distances for each group was: 1.04 ± 0.39 cm in the lower lung, 0.56 ± 0.14 cm in the medial lung, and 0.30 ± 0.06 cm in the upper lung. Conclusion: Tumors in the lower lung are most susceptible to excessive motion and daily variation, and would benefit most from continuous motion tracking and gating. Those in the medial lobe might be at moderate risk. The upper lobes have limited motion. These results can guide different motion management strategies

Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

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Ito, Masaoki; Miyata, Yoshihiro; Hirano, Shoko; Kimura, Shingo; Irisuna, Fumiko; Ikeda, Kyoko; Kushitani, Kei; Tsutani, Yasuhiro; Ueda, Daisuke; Tsubokawa, Norifumi; Takeshima, Yukio; Okada, Morihito

2017-12-12

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

Cerebral metastases from lung carcinoma: neurological and CT correlation: work in progress

International Nuclear Information System (INIS)

Tarver, R.D.; Richmond, B.D.; Klatte, E.C.

1984-01-01

To determine the role of brain CT in neurologically asymptomatic lung cancer patients a review was made of the CT and clinical findings in 279 patients. Brain metastases were found in 94.5% of patients with specific abnormal neurological findings, 26.6% of patients with vague neurological signs and symptoms, 11% of patients with oat cell carcinoma and a normal neurological examination, and 40% of patients with adenocarcinoma and a normal neurological examination. Brain metastasis was not seen on CT in the 29 patients with squamous cell carcinoma and a normal neurological examination. It is concluded that brain CT is useful for the detection of occult brain metastases, particularly oat cell carcinoma and adenocarcinoma, in neurologically asymptomatic lung cancer patients

Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma

International Nuclear Information System (INIS)

Toyohira, Ken; Yasumoto, Kosei; Manabe, Hideo; Ohta, Mitsuo; Terashima, Hiromi

1979-01-01

Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I and II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size. (author)

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

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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.

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

International Nuclear Information System (INIS)

Lee, Danny; Greer, Peter B.; Ludbrook, Joanna; Arm, Jameen; Hunter, Perry; Pollock, Sean; Makhija, Kuldeep; O'brien, Ricky T.; Kim, Taeho; Keall, Paul

2016-01-01

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.

Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis

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Walter, Robert Fred Henry; Werner, Robert; Ting, Saskia; Vollbrecht, Claudia; Theegarten, Dirk; Christoph, Daniel Christian; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Mairinger, Fabian Dominik

2015-01-01

Background Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Materials and Methods Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. Results ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Conclusion Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC. PMID:26008974

Detection of cytoskeletal proteins in small cell lung carcinoma

Czech Academy of Sciences Publication Activity Database

Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

1999-01-01

Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

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.

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

iNOS expression and biosynthesis of nitric oxide metabolites in the course of tumor growth of different histogenesis

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V. P. Deryagina

2016-01-01

Full Text Available The dynamics of the production of nitric oxide (NO metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.

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.

Rare Case of Duodenal Metastasis From Pulmonary Squamous Cell Carcinoma

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Zain Memon DO

2017-10-01

Full Text Available Pulmonary squamous cell carcinoma is the second most common non–small cell malignancy of the lung. It commonly metastasizes to the adrenal glands, bone, liver, brain, and kidneys. Most occurrences of metastatic squamous cell carcinoma involving the gastrointestinal tract originate from primary lung tumors. Metastasis to the duodenum, however, is exceedingly rare, with very few cases of stomach or duodenal involvement described in the literature. We report the case of a patient with stage IV pulmonary squamous cell carcinoma metastasizing to the duodenum with an uncommon presentation to add to the paucity of literature available regarding this rare finding.

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

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Yu-Chun Wei

Full Text Available To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide in the determination of metabolic tumor volume (MTV with micro-PET in lewis lung carcinoma (LLC tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG PET.All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD and 18F-FDG metabolic tumor volume (VFDG were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath was measured in vitro after the xenografts were removed.A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3, 0.61±0.37 cm3 (range,0.15~1.86 cm3, and 1.24±0.53 cm3 (range,0.17~2.20 cm3, respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001 than with VFDG (R = 0.584,P<0.001.18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

Efficiency of lipofection combined with hyperthermia in Lewis lung carcinoma cells and a rodent pleural dissemination model of lung carcinoma.

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Okita, Atsushi; Mushiake, Hiroyuki; Tsukuda, Kazunori; Aoe, Motoi; Murakami, Masakazu; Andou, Akio; Shimizu, Nobuyoshi

2004-06-01

We have previously reported that hyperthermia at 41 degrees C enhanced lipofection-mediated gene transduction into cultured cells. In this study, we adapted hyperthermia technique to novel cationic liposome (Lipofectamine 2000) mediated gene transfection into Lewis lung carcinoma cells in vitro and in vivo. In vitro, transfection efficiencies were 38.9+/-3.3% by lipofection alone and 52.1+/-2.6% by lipofection with hyperthermia for 30 min, and 62.5+/-5.5% and 81.4+/-3.2% for 1 h, respectively. Hyperthermia significantly enhanced gene transfection efficiency 1.2-1.4 times more than that with lipofection only. We also evaluated the effect of hyperthermia with a pleural dissemination model of lung carcinoma of mice. We developed a model which was well-tolerated with hyperthermia with lipofection by the mice. In spite of repeated treatments, transfection efficiencies were very low and we could not show the augmentation of gene transfection by hyperthermia. Though Lipofectamine 2000 showed strong gene transduction effect and hyperthermia augmented its effect in vitro, further evaluation is needed to adapt both techniques in vivo.

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

ABT-263 (Fig. 2I and SI Appendix, Fig. S6A). We therefore sought to identify pharmacological strategies that could suppress MCL-1 levels and increase...resonance imaging ( MRI ) of the thorax was performed 1 day before starting treatment and on day 21 of treatment, and lung tumor volumes pre- and...spread on MRI were included in the analysis. Tumors progressed in all untreated animals (n = 7), although we observed significant variability in the

Hepatic vein tumor thrombus as a risk factor for excessive pulmonary deposition of microspheres during TheraSphere therapy for unresectable hepatocellular carcinoma.

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Fleming, Chad J; Andrews, James C; Wiseman, Gregory A; Gansen, Denise N; Roberts, Lewis R

2009-11-01

To evaluate the impact of identifiable hepatic vein tumor thrombus on the ability to safely deliver TheraSphere (yttrium 90-containing glass microspheres) for the treatment of hepatocellular carcinoma (HCC). A retrospective review was performed of 87 patients (71 men, 16 women; mean age, 64.5 years; age range, 25-83 y) referred for TheraSphere therapy for HCC during a 2-year period between April 2005 and May 2007. Evaluation included contrast-enhanced computed tomography or magnetic resonance imaging, selective mesenteric angiography, and radionuclide perfusion scintigraphy to measure the arteriovenous shunting through the tumor. Of the 87 patients, 83 underwent angiography and perfusion scintigraphy; 53 were ultimately treated with 65 glass microsphere infusions. Twelve of 83 were identified as having tumor thrombus in a hepatic vein or extending into the inferior vena cava. The mean lung shunt for the patients with hepatic vein tumor thrombus was 30% (range, 11%-60%), compared with 8.2% (range, 3%-23%) for patients without identifiable tumor thrombus. Two of the 12 patients were treated with reduced doses of glass microspheres, and the remaining 10 were offered alternative therapies. The presence of hepatic vein tumor thrombus is a risk factor for an increased lung shunt that may prohibit delivery of a therapeutic dose of TheraSphere to hepatic tumor.

Influence of quartz exposure on lung cancer types in cases of lymph node-only silicosis and lung silicosis in German uranium miners.

Science.gov (United States)

Mielke, Stefan; Taeger, Dirk; Weitmann, Kerstin; Brüning, Thomas; Hoffmann, Wolfgang

2018-05-04

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.

Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

Science.gov (United States)

Barresi, Valeria; Branca, Giovanni; Ieni, Antonio; Rigoli, Luciana; Tuccari, Giovanni; Caruso, Rosario Alberto

2015-05-14

To identify those with a micropapillary pattern, ascertain relative frequency and document clinicopathological characteristics by reviewing gastric carcinomas. One hundred and fifty-one patients diagnosed with gastric cancer who underwent gastrectomy were retrospectively studied and the presence of a regional invasive micropapillary component was evaluated by light microscopy. All available hematoxylin-eosin (HE)-stained slides were histologically reviewed and 5 tumors were selected as putative micropapillary carcinoma when cancer cell clusters without a vascular core within empty lymphatic-like space comprised at least 5% of the tumor. Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an anti-mucin 1 (MUC1) antibody (clone MA695) to detect the characteristic inside-out pattern and with D2-40 antibody to determine the presence of intratumoral lymph vessels. Detection of intraepithelial neutrophil apoptosis was evaluated in consecutive histological tissue sections by three independent methods, namely light microscopy with HE staining, the conventional terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemistry for activated caspase-3 (clone C92-605). Among 151 gastric cancers resected for cure, 5 (3.3%) were adenocarcinomas with a micropapillary component. Four of the patients died of disease from 6 to 23 mo and one patient was alive with metastases at 9 mo. All patients had advanced-stage cancer (≥ pT2) and lymph node metastasis. Positive MUC1 immunostaining on the stroma-facing surface (inside-out pattern) of the carcinomatous cluster cells, together with negative immunostaining for D2-40 in the cells limiting lymphatic-like spaces, confirmed the true micropapillary pattern in these gastric neoplasms. In all five cases, several micropapillae were infiltrated by neutrophils. HE staining, TUNEL assay and immunostaining for caspase-3 demonstrated apoptotic neutrophils within

4D-MRI analysis of lung tumor motion in patients with hemidiaphragmatic paralysis

International Nuclear Information System (INIS)

Dinkel, Julien; Hintze, Christian; Tetzlaff, Ralf; Huber, Peter E.; Herfarth, Klaus; Debus, Juergen; Kauczor, Hans U.; Thieke, Christian

2009-01-01

Purpose: To investigate the complex breathing patterns in patients with hemidiaphragmatic paralysis due to malignant infiltration using four-dimensional magnetic resonance imaging (4D-MRI). Patients and methods: Seven patients with bronchial carcinoma infiltrating the phrenic nerve were examined using 1.5 T MRI. The motion of the tumor and of both hemi-diaphragms were measured on dynamic 2D TrueFISP and 4D FLASH MRI sequences. Results: For each patient, 3-6 breathing cycles were recorded. The respiratory-induced mean cranio-caudal displacement of the tumor was 6.6 mm (±2.8 SD). The mean displacement anterior-posterior was 7.4 mm (±2.6), while right-left movement was about 7.4 mm (±4.5). The mediastinum moved sidewards during inspiration, realizing a 'mediastinal shift'. The paralyzed hemidiaphragm and the tumor showed a paradox motion during respiration in five patients. In two patients, the affected hemidiaphragm had a regular, however minimal and asynchronous motion during respiration. Respiratory variability of both tumor and diaphragm motions was about 20% although patients were instructed to breath normally. The findings showed significant differences compared to breathing patterns of patients without diaphragm dysfunction. Conclusion: 4D-MRI is a promising tool to analyze complex breathing patterns in patients with lung tumors. It should be considered for use in planning of radiotherapy to account for individual tumor motion.

[Lung metastases: tumor reduction as an oncologic concept].

Science.gov (United States)

Dienemann, H; Hoffmann, H; Trainer, C; Muley, T

1998-01-01

The principle of surgery for lung metastases is the removal of all lesions in the lung that are either visible or detectable by palpation. This may be combined with complete dissection of all ipsilateral lymph nodes. Therefore, "tumor reduction" rather than "complete" or "radical resection" may be an adequate description of this surgical approach. Since the dissemination of--macroscopically not detectable--tumor cells represents the major mannerism of every metastatic disease, any local therapy appears to be a discrepancy. However, in most cases the rationale of surgery for lung metastases is the lack of effective systemic therapy and the low morbidity of surgery, along with up to 60% 5-year survival rates.

More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells

International Nuclear Information System (INIS)

Zhang, Si-yang; Hui, Lin-ping; Li, Chun-yan; Gao, Jian; Cui, Ze-shi; Qiu, Xue-shan

2016-01-01

Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. The purpose of this study was to explore the function of BDNF in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The expression of BDNF was examined in 110 samples of lung SCC and ADC by immunohistochemistry. The protein level of BDNF was examined in 25 lung SCC or ADC samples and paired non-tumors by western blot. BDNF expression was also evaluated in human bronchial epithelial cells (HBE) and 4 lung cancer cell lines using western blot. Three BDNF mRNA variants containing exons IV, VI and IX were evaluated in HBE, two SCC (SK, LK2) and two ADC (A549, LTE) cell lines by RT-PCR. The expression and secretion of BDNF were also determined in cells using western blot and ELISA. Then the shRNA specific for BDNF was transfected into LK2 or A549 cells to further elucidate the BDNF knockdown on cell proliferation, apoptosis and invasion, which were confirmed by MTT, flow cytometry and transwell examinations. 71.8 % (79 out of 110) of lung SCC and ADC samples were detected positive BDNF, and high expression of BDNF was significantly correlated with histological type and T stage. Compared with non-tumorous counterparts, BDNF was apparently overexpressed in SCC and ADC tissues. In cell studies, the extensive expression and secretion of BDNF were demonstrated in lung cancer cells compared with HBE cells. Interestingly, the expressions of BDNF mRNA variant IV and VI were identical in all cells examined. However, more expression of BDNF mRNA variant IX was found in SK and LK2 cells. The apoptotic cells were increased, and the cell proliferation and invasion were both attenuated once the expression of BDNF was inhibited. When retreated by rhBDNF, BDNF knockdown cells showed less apoptotic or more proliferative and invasive. Our data show that BDNF probably facilitates the tumorigenesis of lung SCC and ADC. The expression of BDNF m

Invasive lobular carcinoma co-existing with benign phylloides tumor

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S Shrestha

2014-04-01

Full Text Available Phylloides tumor constitutes less than 1% of all breast tumors and 2 - 3% of fibroepithelial breast tumors. Several histological parameters should be evaluated, including stromal cellularity, atypia, mitoses, stromal overgrowth, infiltrative borders, and presence or absence of necrosis. Here we report a case of a 60 years- old female who presented with left breast lump. Fine needle aspiration cytology was done which suggested epithelial hyperplasia with fibrocystic changes. Biopsy was performed which showed predominance of stromal hypercellularity with proliferation of spindle cells (no atypia, mitosis and stromal overgrowth were noticed. However, a focus showed proliferation of discohesive tumor cells arranged singly and in single file. A diagnosis of benign phylloides tumor with foci of invasive lobular carcinoma was made. The diagnosis was confirmed with IHC which showed intense 80%positivity for estrogen and progesterone receptor and spindle cells showing positivity for bcl-2. In situ lobular carcinoma component was not observed. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10321   Journal of Pathology of Nepal (2014 Vol. 4, 597-599

Evaluation of connectivity map-discovered celastrol as a radiosensitizing agent in a murine lung carcinoma model: Feasibility study of diffusion-weighted magnetic resonance imaging.

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Hong Young Jun

Full Text Available This study was designed to identify potential radiosensitizing (RS agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI. Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested. Mice inoculated with A549 carcinoma cells were treated with single ionizing radiation (SIR, single celastrol (SC, or celastrol-combined ionizing radiation (CCIR. Changes in radiosensitization over time were assessed using DW-MRI before and at 3, 6, and 12 days after therapy initiation. The tumors were stained with hematoxylin and eosin at 6 and 12 days after therapy. The percentage change in the apparent diffusion coefficient (ADC value in the CCIR group was significantly higher than that in the SC and SIR group on the 12th day (Mann-Whitney U-test, p = 0.05; Kruskal-Wallis test, p < 0.05. A significant correlation (Spearman's rho correlation coefficient of 0.713, p = 0.001 was observed between the mean percentage tumor necrotic area and the mean ADC values after therapy initiation. These results suggest that the novel radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation (IR, thereby maximizing the therapeutic effect of radiation in non-small cell lung carcinoma. In addition, DW-MRI is a useful noninvasive tool to monitor the effects of RS agents by assessing cellularity changes and sequential therapeutic responses.

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

International Nuclear Information System (INIS)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.; Lichtenberg, T.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, β-HCG, and β/sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serum the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and β/sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum β-HCG was normal in all patients. According to these results serum ferritin, TPA, and β/sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum β/sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and β/sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases

Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

International Nuclear Information System (INIS)

Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

2014-01-01

Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

Elective brain irradiation in patients with small-cell carcinoma of the lung: preliminary report

International Nuclear Information System (INIS)

Katsenis, A.T.; Karpasitis, N.; Giannakakis, D.; Maragoudakis, N.; Kiparissiadis, P.

1982-01-01

The brain is a common site of metastases in small-cell carcinoma of the lung. Prophylactic brain irradiation with doses of 4000-4500 rads in 3-4 weeks appears to decrease the occurrence of brain metastases although it does not prevent this completely. In a group of patients with small-cell carcinoma of the lung and without evidence of brain metastases, the authors review the site and extent of the primary, the methods of treatment, the techniques of brain irradiation, and the relapses rate in relation to the status of the primary and the rate of brain metastases in another group without prophylactic brain irradiation. They further attempt to investigate combined modalities of treatment which would prolong life and prevent neurological complications in the small number of long survivors with small-cell carcinoma of the lung. (Auth.)

CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

International Nuclear Information System (INIS)

Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

1994-01-01

It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis.

Science.gov (United States)

Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-10-10

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16-1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50-4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046-1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103-1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393-7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis.

Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

Directory of Open Access Journals (Sweden)

Siwen WANG

2011-09-01

Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

Unravelling the Long Non-Coding RNA Profile of Undifferentiated Large Cell Lung Carcinoma.

Science.gov (United States)

Shukla, Sudhanshu

2018-02-05

Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9-9% of total lung cancers. Recently, RNA-seq based studies have revealed major genomic aberrations in LCLC. In this study, we aim to identify long non-coding RNAs (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile of LCLC and other non-small cell lung carcinoma (NSCLC) was downloaded from Gene Expression Omnibus (GEO) and analyzed. Using 10 LCLC samples, we found that 18% of all the annotated LncRNAs are expressed in LCLC samples. Among 1794 expressed LncRNAs, 11 were overexpressed and 14 were downregulated in LCLC compared to normal samples. Based on receiver operating characteristic (ROC) analysis, we showed that the top five differentially expressed LncRNAs were able to differentiate between LCLC and normal samples with high sensitivity and specificity. Guilt by association analysis using genes correlating with differentially expressed LncRNAs identified several cancer-associated pathways, suggesting the role of these deregulated LncRNA in LCLC biology. We also identified the LncRNA differentially expressed in LCLC compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD). We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD. Interestingly, LCLC had more downregulated LncRNA compared to LUAD and LUSC. Our study provides novel insight into LncRNA deregulation in LCLC. This study also finds tools to diagnose LCLC and differentiate LCLC with other Non-Small Cell Lung Cancer.

Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice.

Science.gov (United States)

He, Quan; Wang, Fangfei; Honda, Takashi; Lindquist, Diana M; Dillman, Jonathan R; Timchenko, Nikolai A; Redington, Andrew N

2017-10-01

Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular carcinoma cell proliferation, invasion, and migration. We have shown that miR-144, injected intravenously, is taken up by the liver and induces endogenous hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor-suppressive effects on liver tumor development in vivo. The effects of miR-144 on tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body weight but significantly reduced diethylnitrosamine-induced liver enlargement compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine-induced liver tumor number but reduced the tumor size above 50%, as evaluated by magnetic resonance imaging (scrambled microRNA 23.07 ± 5.67 vs miR-144 10.38 ± 2.62, p hepatocellular carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic strategy to suppress tumor growth in hepatocellular carcinoma.

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

Molecular biologic study about the non-small cell lung carcinoma (2) : p53 gene alteration in non-small cell lung carcinoma

International Nuclear Information System (INIS)

Park, Jong Ho; Zo, Jae Ill; Paik, Hee Jong; Kim, Mi Hee

1996-12-01

The main purpose of this research was to identify of the p53 and 3p gene alteration in non-small cell lung cancer patients residing in Korea. Furthermore, we analyzed the relationship between the p53 and 3p gene alterations and the clinicopathologic results of lung cancer patients. And we have investigated the role of PCR-LOH in analyzing tumor samples for LOH of defined chromosomal loci. We have used the 40 samples obtained from the lung cancer patients who were diagnosed and operated curatively at Korea Cancer Center Hospital. We have isolated the high molecular weight. DNA from the tumors and normal tissues. And we have amplified the DNA with PCR method and used the microsatellite assay method to detect the altered p53 and 3p gene. The conclusions were as follow: 1) The 3p gene alteration was observed in 9/39 (23.1%) and p53 gene alteration was observed in 15/40 (37.5%) of resected non-small cell lung cancer. 2) There was no correlations between the 3p or p53 gene alterations and prognosis of patients, but further study is necessary. 3) PCR-LOH is a very useful tool for analyzing small amount of tumor samples for loss of heterozygosity of defined chromosomal loci. (author). 10 refs

Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

LENUS (Irish Health Repository)

Canney, A

2012-02-01

Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

Differentiated thyroid carcinomas: prediction of tumor invasion with MR imaging

International Nuclear Information System (INIS)

Takashima, S.; Takayama, F.; Wang, Q.; Kawakami, S.; Saito, A.; Sone, S.; Kobayashi, S.

2000-01-01

Purpose: To assess diagnostic accuracy for tumor invasion of surrounding organs by measurement of tumor circumferences on MR images in patients with differentiated thyroid carcinomas. Material and Methods: Surgical and MR imaging findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7 recurrent lesions) were retrospectively reviewed. The degrees of circumference of tumor encroachment to the organs were measured, and the measurements and morphologic diagnosis of tumor invasion made by a head and neck radiologist were compared with surgical and pathologic findings using receiver operating characteristic curves. Results: Diagnosis of tumor invasion by the radiologist was superior to the measurements of the carotid artery and cartilage, while the reverse was true for the trachea and esophagus. However, no statistical differences were noted between them for each structure. Optimal thresholds for tumor invasion were 90 deg or more for the cartilage (94% accuracy) and esophagus (86% accuracy), 135 deg or more for the trachea (86% accuracy), and 225 deg or more for the carotid artery (90% accuracy). Conclusion: Tumor invasion was more accurately diagnosed by measurement of tumor circumferences of each organ on MR images

FDG-PET on Irradiated Brain Tumor: Ten Years' Summary

International Nuclear Information System (INIS)

Wang, S.X.; Boethius, J.; Ericson, K.

2006-01-01

Purpose: To evaluate FDG-PET in post-radiotherapy differentiation of tumor recurrence/malignant degeneration and radiation reaction, and to assess the role of PET in terms of survival. Material and Methods: 117 consecutive patients with a total of 156 FDG-PET examinations with positive but non-diagnostic MRI and/or CT were included. Final diagnosis was based on histopathology or correlated with radiologic and clinical follow-up. Brain metastases from lung carcinomas were further studied separately. Survival time was analysed using the Kaplan-Meier method. Results: There were 61 true-positive, 2 false-positive, 15 false-negative, and 51 true-negative PET examinations; 5 positive and 22 negative PET examinations were indeterminate. The positive predictive value of a PET examination was 96% in all and 100% in brain metastases from lung carcinoma. The negative predictive value based on the histopathologic results was 55.6%. Survival time was significantly longer in patients with negative PET. Conclusion: FDG-PET is a valuable tool in the detection of tumor recurrence, especially lung carcinoma metastasis. FDG uptake is a prognostic marker

Local Control of Lung Derived Tumors by Diffusing Alpha-Emitting Atoms Released From Intratumoral Wires Loaded With Radium-224

International Nuclear Information System (INIS)

Cooks, Tomer; Schmidt, Michael; Bittan, Hadas; Lazarov, Elinor; Arazi, Lior; Kelson, Itzhak; Keisari, Yona

2009-01-01

Purpose: Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520). Methods and Materials: An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with 224 Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors in athymic mice. The efficacy of the short-lived daughters of 224 Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography. Results: The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles. Conclusions: Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

2011-01-01

This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis

International Nuclear Information System (INIS)

Jiang, Wen-guo; Zhen, Yong-su; Lu, Xin-an; Shang, Bo-yang; Fu, Yan; Zhang, Sheng-hua; Zhou, Daifu; Li, Liang; Li, Yi; Luo, Yongzhang

2013-01-01

Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety. In this study, we designed and obtained two new endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the wound healing assay and tube formation assay and the cytotoxicity of their enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was evaluated with human lung carcinoma PG-BE1 xenograft and the experimental metastasis model of 4T1-luc breast cancer. ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice. The ES-based fusion protein therapy provides some fundamental information for further drug development. Targeting both tumor vasculature and tumor cells by endostatin

Histological evaluation of lung cancer with T2-weighted magnetic resonance images

International Nuclear Information System (INIS)

Ohta, Takashi; Matsuura, Yoshifumi; Shioya, Sumie; Ohta, Yasuyo

1995-01-01

We investigated the differences in signal intensity of lung cancer tissue and non-cancerous lung tissues on T 2 -weighted magnetic resonance (MR) images. MR images were obtained from patients with squamous cell carcinoma (n=6), adenocarcinoma (n=5), small cell carcinoma (n=5), and large cell carcinoma (n=1). To compare the MR signal intensity between tissues, we calculated the signal intensity ratios for tumor/skeletal muscle and lung/skeletal muscle. The MR signal intensity for each tissue was measured with a densitometer and T 2 -weighted MR images with a similar window and a center. The value of the signal intensity ratio for squamous cell carcinoma (3.26±0.76) was greater than those for adenocarcinoma (1.99±0.50, p<0.05), small cell carcinoma (2.35±0.60), large cell carcinoma (2.46), and non-cancerous lung tissues (1.70±0.68, p<0.02). The values of the MR signal intensity ratio for non-cancerous lung tissues were 2.00 for a collapsed lung, 0.93 for a fibrotic lung, and 2.18 for a fibrotic lung with obstructive pneumonia. The results suggest that the MR signal intensity ratio for pathologic tissues/normal skeletal muscle can be a useful indicator for qualitative and quantitative MR imaging diagnosis. (author)

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

Directory of Open Access Journals (Sweden)

Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

Presence of lung metastases in bitches affected by malignant mammary neoplasms in Medellin (Colombia

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Brigitte Gómez J.

2012-08-01

Full Text Available Objective. To define the presence of lung metastasis in bitches with malignant mammary neoplasms. Materials and methods. Thirty female dogs that were attended at Veterinary Hospital (University of Antioquia, Medellin, Colombia were selected for the study. At consultation clinical variables and grade of mammary and inguinal lymph node compromise were registered. Latero-lateral and ventral-dorsal radiographic images of thorax were done for identification of radiographic lesions suggestive of lung metastasis. At surgery biopsies of affected mammary glands were taken for histopathological study and classification of tumors. Data were analyzed by descriptive statistics. Results. The average (± standard error age at clinical diagnosis was 10.87±2.65 year old. French poodle (46.6% cross-breed (13.3% and Schnauzer (10% were the breeds most frequently affected by mammary tumors. The most frequent tumor found was carcinoma (81%, followed by adenoma (8.1%, and other types (10.8%. The most frequently affected mammary glands by tumors were the right and the left inguinal glands (70% and 66.6%, respectively. Five out of 30 bitches (16.6% had lung metastasis according to radiographic examination. From this group of dogs, 4 out of 5 neoplasms (80% were diagnosed as complex carcinoma by histopathology diagnosis. Conclusions. We provide evidence suggesting that complex carcinoma is the most frequent mammary tumor in bitches in our city and it is highly related to lung metastasis.

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

DEFF Research Database (Denmark)

Bak, Martin; Teglbjaerg, P S

1989-01-01

reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen......Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation...

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...... 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...

Preparation of 99Tcm-CLP imaging probe of lung carcinoma

International Nuclear Information System (INIS)

Qiang Yonggang; Liao Yonghua

2004-01-01

The process of preparing an imaging micro-probe 99 Tc m -CLP from bovine nose cartilage is described in detail. Both labeled rate and radiochemical purity of 99 Tc m -CLP are greater than 90%, and KA is 1.12 x 10 9 L/mol in vitro. After the Balb/c nu/nu mice with lung cancer were intravenously injected by the 99 Tc m -CLP, the radioactivity was found to be well concentrated at the lung-cancer region, which suggests that the 99 Tc m -CLP micro-probe can be used in imaging study of lung carcinoma. (authors)

Preliminary study of spectral CT imaging in the differential diagnosis of metastatic lymphadenopathy due to various tumors

International Nuclear Information System (INIS)

Liu Jingang; Liu Ya; Li Lixin

2011-01-01

Objective: To investigate the feasibility of differentiating lymph node metastases of four types of primary tumors (lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma) using gemstone spectral imaging (GSI). Methods: Three cases with lymphoma (28 lymph node), five cases with lung adenocarcinoma (30 lymph node), four cases with lung squamous cell carcinoma (24 lymph node) and two cases with cholangiocarcinoma (10 lymph node) were evaluated by germstona spectra imaging CT scans. Imaging protocol included unenhanced conventional CT scan (120 kVp), enhanced GSI (80/140 kVp) on arterial phase and conventional CT scan (120 kVp) on portal phase. CT attenuation values of lymph nodes in the monochromatic images at Il sets of keV levels (40- 140 keV, 10 keV step) and the iodine and water contents of these lymph nodes were measured. All results were analyzed with ANOVA and t test. Results: The optimal monochromatic level was 70 keV for the optimal contrast-noise ratio (CNR) of metastatic lymphadenopathy. The CT attenuation values of metastatic lymphadenopathy were (81.36±9.81), (58.33±21.55), (56.47±10.62) and (73.57±4.43) HU, respectively, at 70 keV (F=17.29, P 0.05). The iodine contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were (1.93±0.04), (1.16±0.15), (1.25±0.21) and (1.44±0.04) g/L, respectively. The water contents of lymphoma, lung adenocarcinoma, lung squamous cell carcinoma and cholangiocarcinoma were (1029.40±20.85), (1024.98±11.19), (1022.12±12.94) and (1030.87±10.10) g/L, respectively. Except between lung squamous cell carcinoma and lung adenocarcinoma, the differences in the iodine contents of metastatic lymphadenopathy were significant among tumors (P 0.05 ). Conclusions: Although CT spectral imaging fails to differentiate metastatic lymphadenopathy of lung adenocarcinoma and lung squamous cell carcinoma, it is also a promising method of distinguishing metastatic

Surgical excision of lung metastases from squamous carcinoma of ...

African Journals Online (AJOL)

These 2 case reports serveto emphasizetwo important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii). in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result -in cure.

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

Science.gov (United States)

Knips, Jill; Czech-Sioli, Manja; Spohn, Michael; Heiland, Max; Moll, Ingrid; Grundhoff, Adam; Schumacher, Udo; Fischer, Nicole

2017-07-01

Merkel cell carcinoma (MCC) is an aggressive skin cancer entity that frequently leads to rapid death due to its high propensity to metastasize. The etiology of most MCC cases is linked to Merkel cell polyomavirus (MCPyV), a virus which is monoclonally integrated in up to 95% of tumors. While there are presently no animal models to study the role of authentic MCPyV infection on transformation, tumorigenesis or metastasis formation, xenograft mouse models employing engrafted MCC-derived cell lines (MCCL) represent a promising approach to study certain aspects of MCC pathogenesis. Here, the two MCPyV-positive MCC cell lines WaGa and MKL-1 were subcutaneously engrafted in scid mice. Engraftment of both MCC cell lines resulted in the appearance of circulating tumor cells and metastasis formation, with WaGa-engrafted mice showing a significantly shorter survival time as well as increased numbers of spontaneous lung metastases compared to MKL-1 mice. Interestingly, explanted tumors compared to parental cell lines exhibit an upregulation of MCPyV sT-Antigen expression in all tumors, with WaGa tumors showing significantly higher sT-Antigen expression than MKL-1 tumors. RNA-Seq analysis of explanted tumors and parental cell lines furthermore revealed that in the more aggressive WaGa tumors, genes involved in inflammatory response, growth factor activity and Wnt signalling pathway are significantly upregulated, suggesting that sT-Antigen is the driver of the observed differences in metastasis formation. © 2017 UICC.

Pyruvate Dehydrogenase and Pyruvate Dehydrogenase Kinase Expression in Non Small Cell Lung Cancer and Tumor-Associated Stroma

Directory of Open Access Journals (Sweden)

Michael I. Koukourakis

2005-01-01

Full Text Available Pyruvate dehydrogenase (PDH catalyzes the conversion of pyruvate to acetyl-coenzyme A, which enters into the Krebs cycle, providing adenosine triphosphate (ATP to the cell. PDH activity is under the control of pyruvate dehydrogenase kinases (PDKs. Under hypoxic conditions, conversion of pyruvate to lactate occurs, a reaction catalyzed by lactate dehydrogenase 5 (LDH5. In cancer cells, however, pyruvate is transformed to lactate occurs, regardless of the presence of oxygen (aerobic glycolysis/Warburg effect. Although hypoxic intratumoral conditions account for HIFia stabilization and induction of anaerobic metabolism, recent data suggest that high pyruvate concentrations also result in HIFia stabilization independently of hypoxia. In the present immunohistochemical study, we provide evidence that the PDH/PDK pathway is repressed in 73% of non small cell lung carcinomas, which may be a key reason for HIFia stabilization and “aerobic glycolysis.” However, about half of PDHdeficient carcinomas are not able to switch on the HIF pathway, and patients harboring these tumors have an excellent postoperative outcome. A small subgroup of clinically aggressive tumors maintains a coherent PDH and HIF/LDH5 expression. In contrast to cancer cells, fibroblasts in the tumor-supporting stroma exhibit an intense PDH but reduced PDK1 expression favoring maximum PDH activity. This means that stroma may use lactic acid produced by tumor cells, preventing the creation of an intolerable intratumoral acidic environment at the same time.

Dynamic FDG-PET Imaging to Differentiate Malignancies from Inflammation in Subcutaneous and In Situ Mouse Model for Non-Small Cell Lung Carcinoma (NSCLC).

Science.gov (United States)

Yang, Zhen; Zan, Yunlong; Zheng, Xiujuan; Hai, Wangxi; Chen, Kewei; Huang, Qiu; Xu, Yuhong; Peng, Jinliang

2015-01-01

[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been widely used in oncologic procedures such as tumor diagnosis and staging. However, false-positive rates have been high, unacceptable and mainly caused by inflammatory lesions. Misinterpretations take place especially when non-subcutaneous inflammations appear at the tumor site, for instance in the lung. The aim of the current study is to evaluate the use of dynamic PET imaging procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma (NSCLC) from inflammation, and estimate the kinetics of inflammations in various locations. Dynamic FDG-PET was performed on 33 female mice inoculated with tumor and/or inflammation subcutaneously or inside the lung. Standardized Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx rate constant (Ki) of compartmental modeling from dynamic imaging were obtained. Static and kinetic data from different lesions (tumor and inflammations) or different locations (subcutaneous, in situ and spontaneous group) were compared. Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (pPET based SUVmax, both subcutaneous and in situ inflammations and malignancies can be differentiated via dynamic FDG-PET based Ki. Moreover, Values of influx rate constant Ki from compartmental modeling can offer an assessment for inflammations at different locations of the body, which also implies further validation is necessary before the replacement of in situ inflammation with its subcutaneous counterpart in animal experiments.

Loss of expression of BAP1 is very rare in non-small cell lung carcinoma.

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Andrici, Juliana; Parkhill, Thomas R; Jung, Jason; Wardell, Kathryn L; Verdonk, Brandon; Singh, Arjun; Sioson, Loretta; Clarkson, Adele; Watson, Nicole; Sheen, Amy; Farzin, Mahtab; Toon, Christopher W; Gill, Anthony J

2016-06-01

Germline mutations of the BAP1 gene have been implicated in a cancer predisposition syndrome which includes mesothelioma, uveal melanoma, cutaneous melanocytic lesions, renal cell carcinoma, and possibly other malignancies. Double hit inactivation of BAP1 with subsequent loss of expression of the BAP1 protein also occurs in approximately 50% of mesotheliomas. The link between BAP1 mutation and lung cancer is yet to be fully explored. We sought to assess BAP1 expression in a large cohort of lung cancers undergoing surgery with curative intent. We searched the Anatomical Pathology database of our institution for lung cancer patients undergoing surgery with curative intent between 2000 and 2010. Immunohistochemistry for BAP1 was then performed in tissue microarray format. Our cohort included 257 lung cancer patients, of which 155 (60%) were adenocarcinomas and 72 (28%) were squamous cell carcinomas, with no other subtype comprising more than 3%. BAP1 loss of expression was found in only one lung cancer. We conclude that BAP1 mutation occurs very infrequently (0.4%) in non-small cell lung cancer. Given that the pathological differential diagnosis between lung carcinoma and mesothelioma may sometimes be difficult, this finding increases the specificity of loss of expression for BAP1 for the diagnosis of mesothelioma. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

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Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2009-01-01

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

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Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

2011-06-01

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Dissemination of Walker 256 carcinoma cells to rat skeletal muscle

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Ueoka, H.; Hayashi, K.; Namba, T.; Grob, D.

1986-01-01

After injection of 10 6 Walker 256 carcinoma cells labelled with 125 I-5-iodo-2'-deoxyuridine into the tail vein, peak concentration in skeletal muscle was 46 cells/g at 60 minutes, which was lower than 169202, 1665, 555, 198 and 133 cells/g, respectively, at 30 or 60 minutes in lung, liver, spleen, kidney and heart. Because skeletal muscle constitutes 37.4% of body weight, the total number of tumor cells was 2323 cells, which was much greater than in spleen, kidney and heart with 238, 271, and 85 cells, respectively, and only less than in lung and liver, at 222857 and 11700 cells, respectively. The total number in skeletal muscle became greater than in liver at 4 hours and than in lung at 24 hours. Ten minutes after injection of 7.5 x 10 6 Walker 256 carcinoma cells into the abdominal aorta of rats, a mean of 31 colony-forming cells were recovered from the gastrocnemius, while 106 cells were recovered from the lung after injection into the tail vein. These results indicate that a large number of viable tumor cells can be arrested in skeletal muscle through circulation. The rare remote metastasis of malignancies into skeletal muscle despite constantly circulating tumor cells does not appear to be due to poor dissemination of tumor cells into muscle but due to unhospitable environment of skeletal muscle

Aquamous cell carcinomas of the lung which presented as numerous polypoid nodules in the tracheobronchial tree: A case report

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Lee, Hyun Gyu; Choi, Yo Won; Yoon, Hyun Jung; Paik, Seung Sam [Hanyang University Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of)

2017-03-15

We report a case of squamous cell carcinomas of the lung, which presented as numerous polypoid nodules in the tracheobronchial tree. They occurred at two years and 7 months after resection of squamous cell carcinoma, which presented as a lung nodule in the left lower lobe, and at 7 months after resection of tracheal squamous cell carcinoma.

Aquamous cell carcinomas of the lung which presented as numerous polypoid nodules in the tracheobronchial tree: A case report

International Nuclear Information System (INIS)

Lee, Hyun Gyu; Choi, Yo Won; Yoon, Hyun Jung; Paik, Seung Sam

2017-01-01

We report a case of squamous cell carcinomas of the lung, which presented as numerous polypoid nodules in the tracheobronchial tree. They occurred at two years and 7 months after resection of squamous cell carcinoma, which presented as a lung nodule in the left lower lobe, and at 7 months after resection of tracheal squamous cell carcinoma

Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

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Jiang C

2016-10-01

Full Text Available Canhua Jiang,1 Shufang Jin,1 Zhisheng Jiang,1 Jie Wang2 1Department of Oral and Maxillofacial Surgery, Xiangya Hospital, 2Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Objective: To investigate the possible mechanisms and effects of silibinin (SIL on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M.Methods: A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3. An experimental adenoid cystic carcinoma (ACC lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples.Results: SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05. The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80% significantly increased, but the positive expression of LC3 in human ACC (42.22% reduced significantly.Conclusion: SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. Keywords: silibinin, adenoid cystic carcinoma, ACC-M cells, autophagy

Radiation therapy alone for early stage non-small cell carcinoma of the lung

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

2002-01-01

To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy along and define the optimal radiotherapeutic regimen for these patients. A retrospective review was performed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 69 Gy. No patients were lost to follow-up. The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and 21%, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and 25%, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was 43%. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented 78% of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm (0% vs 36%). Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70

High frequency of p 16 promoter methylation in non-small cell lung carcinomas from Chile

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LEDA M GUZMAN

2007-01-01

Full Text Available The inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74. When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91% compared with adenocarcinomas (21/30, 70% (p=0.029. In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively. Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent

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

Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters.

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Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

2015-11-21

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

Lung inflammatory pseudo tumor

International Nuclear Information System (INIS)

Veliz, Elizabeth; Leone, Gaetano; Cano, Fernando; Sanchez, Jaime

2005-01-01

The inflammatory pseudo tumor is a non neoplastic process characterized by an irregular growth of inflammatory cells. We described the case of a 38 year-old patient, she went to our institute for a in situ cervix cancer and left lung nodule without breathing symptoms; valued by neumology who did bronchoscopy with biopsy whose result was negative for malignancy. She went to surgery in where we find intraparenquima nodule in felt lingula of approximately 4 cms, we remove it; the result was: Inflammatory pseudotumor. This pathology is a not very frequent, it can develop in diverse regions of the organism, it is frequent in lung. The image tests are not specific for the diagnose, which it is possible only with the biopsy. The treatment is the complete resection. (The author)

Clinical potential of necitumumab in non-small cell lung carcinoma

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Genova C

2016-08-01

Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

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Alper Nesip Manav

2014-01-01

Full Text Available Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung, and gastrointestinal tract for metastatic testicular cancers. Metastasis of urothelial carcinoma (UC to the testis is extremely rare. Two-thirds of upper tract urothelial carcinoma (UTUC is of invasive stage at diagnosis and metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a rare case of metastatic UTUC to the testis which has not been reported before, except one case in the literature. Testicular metastasis of UC should be considered in patients with hematuria and testicular swelling.

'Dancing eyes, dancing feet syndrome' in small cell lung carcinoma.

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Sharma, Chandramohan; Acharya, Mihir; Kumawat, Bansi Lal; Kochar, Abhishek

2014-04-23

A 60-year-old man presented with a 25-day history of acute onset instability of gait, tremulousness of limbs and involuntary eye movements. Examination revealed presence of opsoclonus, myoclonus and ataxia, without any loss of motor power in the limbs. Prompt investigations were directed towards identifying an underlying malignancy which is often associated with this type of clinical scenario. CT of the brain was normal and cerebrospinal fluid examination showed lymphocytic pleocytosis. A cavitatory lesion was found in the right lung base on the high-resolution CT of the chest and histopathological examination of this lung mass showed small cell lung carcinoma. The patient was managed symptomatically with levetiracetam and baclofen and referred to oncology department for resection of the lung mass.

Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

International Nuclear Information System (INIS)

Scholten, Ernst T.; Horeweg, Nanda; Koning, Harry J. de; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Mali, Willem P.T.M.; Jong, Pim A. de

2015-01-01

To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

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Scholten, Ernst T. [University Medical Centre, Department of Radiology, Utrecht (Netherlands); Kennemer Gasthuis, Department of Radiology, Haarlem (Netherlands); Horeweg, Nanda [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Erasmus University Medical Centre, Department of Pulmonary Medicine, Rotterdam (Netherlands); Koning, Harry J. de [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Centre Groningen, Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Mali, Willem P.T.M.; Jong, Pim A. de [University Medical Centre, Department of Radiology, Utrecht (Netherlands)

2015-01-15

To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

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

Does incomplete excision of basal cell carcinoma of the eyelid mean tumor recurrence? A excisão incompleta de carcinoma basocelular da pálpebra implica

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Irena Jankovic

2010-12-01

Full Text Available INTRODUCTION: Basal cell carcinoma is the most common tumor of the eyelid. In this region, reconstruction is complex and damage to healthy tissue should be minimal. Objective: To define the relationship between margin clearance at excision and the recurrence rate of basal cell carcinoma of the eyelid. METHODS: This prospective study was conducted with 111 patients submitted to surgery for basal cell carcinoma of the eyelid between 2001 and 2003 and followed up for a period of five years. The patients were evaluated according to age, tumor site, recurrence rate and margin clearance at excision. RESULTS: No significant association was found between incomplete tumor excision and recurrence except in patients under 56 years of age, female patients and in the case of tumors of the medial canthus. CONCLUSION: A risk of recurrence in incompletely excised basal cell carcinomas of the eyelid was only confirmed in younger patients, females and for tumors of the medial canthus.INTRODUÇÃO: O carcinoma basocelular é o tumor mais comum entre os tumores das pálpebras. Nesta região, a reconstrução é complexa e recomenda-se que haja perda mínima de tecido saudável. OBJETIVO: Para definir a relação entre margem livre de tumor na excisão e taxa de recidiva do carcinoma basocelular das pálpebras. MÉTODOS: Este estudo prospectivo incluiu 111 pacientes operados para remoção de carcinoma basocelular das pálpebras no período de 2001 a 2003, com acompanhamento subsequente de 5 anos. Os pacientes foram avaliados de acordo com a idade, localização do tumor, taxa de recidiva, e margem livre de tumor na excisão. RESULTADOS: Não se encontrou associação significativa entre a excisão incompleta do tumor e casos de recidiva, exceto em pacientes com idade inferior a 56 anos, pacientes do sexo feminino e em tumores do canto medial. CONCLUSÃO: Um risco maior de recidiva de carcinoma basocelular das pálpebras com excisão incompleta foi confirmado

Skeletal metastases of carcinomas of prostate in dependence on tumor size and tumor differentiation

International Nuclear Information System (INIS)

Krause, U.

1981-01-01

153 patients with carcinoma of the prostate underwent holebody skeletal scintiscanning. It resulted that the tendency to the development of skeletal metastases increases with increasing dedifferentiation of the tumor. Also the tumor size correlated with the metastase identification. The tumor dedifferentiation also increased with the tumor size. The findings proved that the early diagnosis of a carcinoma of the prostate is a necessary prerequisite, because a radical total removal can only be curative when any metastases are absent. The comparative evaluation of the diagnostic methods proved the superiority of the nuclear medical examination. In 68% of the cases the roentgenologic examination led to correctly positive results. This investigation showed with 98% a high diagnostic specificity and therefore it should be applied in addition to scintiscanning in order to obtain supplementary information. The alkaline and the acid phosphatase offering an almost identical informative value resulted to be not useful for establishing an early diagnosis of skeletal metastases. It was found that the determination of the blood sedimentation rate and of the lactate dehydrogenase do also not render possible the early diagnosis of skeletal metastases. (orig./MG) [de

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...

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

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Seki, Yasuhiro [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Yoshida, Yukihiro [Department of Surgery, Asahi General Hospital, Chiba (Japan); Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Ishimine, Hisako [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan); Shinozaki-Ushiku, Aya [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Ito, Yoshimasa [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Sumitomo, Kenya [Department of Internal Medicine, JA Kochi Hospital, Kochi (Japan); Nakajima, Jun [Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Michiue, Tatsuo [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Asashima, Makoto, E-mail: asashi@bio.c.u-tokyo.ac.jp [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan)

2014-01-24

Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

International Nuclear Information System (INIS)

Seki, Yasuhiro; Yoshida, Yukihiro; Ishimine, Hisako; Shinozaki-Ushiku, Aya; Ito, Yoshimasa; Sumitomo, Kenya; Nakajima, Jun; Fukayama, Masashi; Michiue, Tatsuo; Asashima, Makoto; Kurisaki, Akira

2014-01-01

Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma

Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

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Amouyal, G; Pernot, S; Déan, C; Cholley, B; Scotté, F; Sapoval, M; Pellerin, O

2017-11-01

The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18 FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18 FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS

Multi-focal lobular carcinoma in situ arising in benign phylodes tumor: A case report

International Nuclear Information System (INIS)

Lee, Taeg Ki; Choi, Chang Hwan; Kim, Youn Jeong; Kim, Mi Young; Lee, Kyung Hee; Cho, Soon Gu

2015-01-01

Coexistent breast malignancy arising in phyllodes tumor is extremely rare, and most of them are incidental reports after surgical excision. Coexistent malignancy in phyllodes tumor can vary from in-situ to invasive carcinoma. Lobular neoplasia is separated into atypical lobular hyperplasia and lobular carcinoma in situ (LCIS). LCIS is known to have a higher risk of developing invasive cancer. We reported imaging findings of multifocal LCIS arising in benign phyllodes tumor

Multi-focal lobular carcinoma in situ arising in benign phylodes tumor: A case report

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Lee, Taeg Ki; Choi, Chang Hwan; Kim, Youn Jeong; Kim, Mi Young; Lee, Kyung Hee; Cho, Soon Gu [Inha University Hospital, Incheon (Korea, Republic of)

2015-08-15

Coexistent breast malignancy arising in phyllodes tumor is extremely rare, and most of them are incidental reports after surgical excision. Coexistent malignancy in phyllodes tumor can vary from in-situ to invasive carcinoma. Lobular neoplasia is separated into atypical lobular hyperplasia and lobular carcinoma in situ (LCIS). LCIS is known to have a higher risk of developing invasive cancer. We reported imaging findings of multifocal LCIS arising in benign phyllodes tumor.

Induction of cancer cell death by proton beam in tumor hypoxic region

International Nuclear Information System (INIS)

Hur, T. R.; Lee, Y. M.; Park, J. W.; Sohn, E. J.

2006-05-01

The physical properties of charged particles such as protons are uniquely suited to target the radiation dose precisely in the tumor. In proton therapy, the Bragg peak is spread out by modulating or degrading the energy of the particles to cover a well defined target volume at a given depth. Due to heterogeneity in the various tumors and end-points as well as in the physical properties of the beams considered, it is difficult to fit the various results into a clear general description of the biological effect of proton in tumor therapy. Tumor hypoxia is a main obstacle to radiotherapy, including gamma-ray. Survived tumor cells under hypoxic region are resistant to radiation and more aggressive to be metastasized. To investigate the dose of proton beam to induce cell death of various tumor cells and hypoxic tumor cells at the Bragg peak in vitro, we used 3 kinds of tumor cells, lung cancer, leukemia and hepatoma cells. Proton beam induces apoptosis in Lewis lung carcinoma cells dose dependently and, slightly in leukemia but not in hepatoma cells at all. Above 1000 gray of proton beam, 60% of cells died even the hypoxic cells in Lewis lung carcinoma cells. But the Molt-4 leukemia cells showed milder effect, 20% cell death by the above 1000 Gray of proton beam and typical resistant pattern (5-10%) of hypoxia in desferrioxamine treated cells. Hepatoma cells (HepG2) were not responsive to proton beam even in rather higher dose (4000G). However, by the gamma-irradiation, Molt-4 was more sensitive than hepatoma or lung cancer cells, but still showed hypoxic resistance. The cell death by proton beam in Lewis lung carcinoma cells was confirmed by PARP cleavage and may be mediated by increased p53. Pro-caspases were also activated and cleaved by the proton beam irradiations for lung cancer cell death. In conclusion, high dose of proton beam (above 1000 gray) may be a good therapeutic radiation even in hypoxic region at the Bragg peak, but further investigations about the

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

Science.gov (United States)

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters

International Nuclear Information System (INIS)

Tehrani, Joubin Nasehi; Wang, Jing; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu

2015-01-01

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney–Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney–Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney–Rivlin material model along left-right, anterior–posterior, and superior–inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation. (paper)

Tumor filodes de mama con metástasis en pulmón Phyllodes tumor of the breast with lung metastasis

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Ernesto Arias Beatón

2012-04-01

Full Text Available Se describe el caso clínico de una paciente de 63 años de edad, quien ingresó en el Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba por presentar tos seca persistente, expectoración escasa (en ocasiones amarillenta, astenia y pérdida de peso. En el examen físico se palpó un tumor en la mama derecha, confirmado a través de ecografía y mamografía. Los resultados de la biopsia por aspiración con aguja fina fueron positivos de células neoplásicas, compatibles con carcinoma. La radiografía de tórax y la tomografía axial computarizada revelaron la presencia de imágenes metastásicas pulmonares, por lo cual se realizó la exéresis del tumor con un margen de seguridad de 2 cm. Mediante el estudio histopatológico se confirmó la existencia de un tumor filodes, de manera que fue preciso indicar 3 ciclos de quimioterapia (esquema CISCYVADACT, del que solo se cumplieron 2, pues la anciana evolucionó desfavorablemente y falleció 3 meses después.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.

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

NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma

OpenAIRE

Rocha, CM; Barros, AS; Goodfellow, BJ; Carreira, IM; Gomes, AA; Sousa, V; Bernardo, J; Carvalho, L; Gil, AM; Duarte, IF

2015-01-01

Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissue...

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

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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.

First clinical evaluation of radioimmunoimaging using anti-human lung cancer monoclonal antibodies

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Zhou Qian

1991-01-01

Anti-human large cell lung cancer monoclonal antibodies (McAb) 2E3 and 6D1 were produced in the laboratory. Immunohistochemical studies and radiobinding assay showed these antibodies possessed high specificity against lung cancer cells. 28 patients with lung masses were investigated with 131 I-labeled McAb 6D1 and/or 2E3 scintigraphy. 19 of them were histologically proven and 13 were diagnosed primary lung carcinoma. Radioimmunoimaging visualized 10/13 of the primary lung cancers with a detection rate of 77%. Only 1 case of the non-cancer patients and a false localization, giving a true negative rate of 83%. Pathologically the squamous cell lung carcinoma had the highest localization and the small cell lung carcinoma next, but the detection rate was 100% for both. The adenocarcinoma of lung was less sensitive to these McAbs, with a detection rate of only 33% (1 of 3 cases). We conclude that radioimmunoimaging with anti-human large cell lung cancer McAbs is more specific and effective in detecting primary lung cancers and differentiating lung masses than with antibodies against other tumor associated antigens

Sensitivity of Tumor Motion Simulation Accuracy to Lung Biomechanical Modeling Approaches and Parameters

OpenAIRE

Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

2015-01-01

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional com...

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.)

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

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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.)

Inguinal lymph node as the only evidence of progressive lung cancer

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Zafer Kocak

2008-09-01

Full Text Available Abstact: Tumours that metastasise to groin nodes most frequently originate in genital and reproductive organs, skin, rectum or anus, or urinary bladder1,2. However, rare cases of inguinal metastases from tumours above the diaphragm have been reported2-5 and only three of them had an inguinal metastasis which was recognised antemortem and reported in detail in the English medical literature3-5. The primary tumours of these cases were malignant mesothelioma, salivary duct and breast carcinoma. In this paper, we report a case of carcinoma of the lung metastatic to an inguinal lymph node as the only evidence of progressive lung cancer. Resumo: Os tumores que metastizam para os gânglios inguinais têm frequentemente origem nos órgãos genitais e reprodutores, na pele, no recto ou ânus, ou na bexiga1,2. Há, no entanto, algumas descrições de casos raros de metástases inguinais de tumores localizados acima do diafragma2-5, e apenas três destes apresentavam uma metástase inguinal reconhecida antes da morte. Estes casos estão detalhadamente descritos na literatura médica de língua inglesa3-5. Os tumores primários destes casos eram mesotelioma maligno e carcinomas do conduto salivar e da mama. Descrevemos um caso de carcinoma do pulmão que metastizou para gânglio inguinal, como única evidência de cancro do pulmão progressivo. Key-words: Non-small cell lung carcinoma, inguinal lymph node, metastasis, disease progression, Palavras-chave: Carcinoma do pulmão de não pequenas células, gânglio inguinal, metástase, progressão da doença

Two-step Raman spectroscopy method for tumor diagnosis

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Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Two-step Raman spectroscopy phase method was proposed for differential diagnosis of malignant tumor in skin and lung tissue. It includes detection of malignant tumor in healthy tissue on first step with identification of concrete cancer type on the second step. Proposed phase method analyze spectral intensity alteration in 1300-1340 and 1640-1680 cm-1 Raman bands in relation to the intensity of the 1450 cm-1 band on first step, and relative differences between RS intensities for tumor area and healthy skin closely adjacent to the lesion on the second step. It was tested more than 40 ex vivo samples of lung tissue and more than 50 in vivo skin tumors. Linear Discriminant Analysis, Quadratic Discriminant Analysis and Support Vector Machine were used for tumors type classification on phase planes. It is shown that two-step phase method allows to reach 88.9% sensitivity and 87.8% specificity for malignant melanoma diagnosis (skin cancer); 100% sensitivity and 81.5% specificity for adenocarcinoma diagnosis (lung cancer); 90.9% sensitivity and 77.8% specificity for squamous cell carcinoma diagnosis (lung cancer).

The expression of GST isoenzymes and p53 in non-small cell lung cancer.

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MĂźzeyyen Ozhavzali

2010-06-01

Full Text Available This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase alpha, pi, mu, theta and p53 in non-small cell lung carcinoma and normal lung tissue from 50 patients. The relationships between expressions of the Glutathione-S-transferase isoenzymes and some clinicopathological features were also examined. Expression of glutathione-S-transferase pi, mu, alpha, theta and p53 was assessed by immunohistochemistry for primary lung carcinomas of 50 patients from the Sanitarium Education and Research Hospital, Ankara lung cancer collection. The relationships between expression of the glutathione-S-transferase isoenzymes, p53 in normal and tumor tissue by Student T test and the clinicopathological data were also examined by Spearman Rank tests. When the normal and tumor tissue of these cases were compared according to their staining intensity and percentage of positive staining, glutathione-S-transferase alpha, pi, mu, theta expressions in tumor cells was significantly higher than normal cells (p<0.05. There was no significant difference in the expression of p53 between normal and tumor cells (p>0.05. When the immunohistochemical results of glutathione-S-transferase isoenzymes and p53 were correlated with the clinical parameters, there were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05.

Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

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Xiaopeng Ma

2017-01-01

Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

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Shujing Shi

Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

Lectin enhancement of the lipofection efficiency in human lung carcinoma cells.

Science.gov (United States)

Yanagihara, K; Cheng, P W

1999-10-18

Poor transfection efficiency of human lung carcinoma cells by lipofection begs further development of more efficient gene delivery strategies. The purpose of this study was to determine whether lectins can improve the lipofection efficiency in lung carcinoma cells. A549, Calu3, and H292 cells grown to 90% confluence were transfected for 18 h with a plasmid DNA containing a beta-galactosidase reporter gene (pCMVlacZ) using lipofectin plus a lectin as the vector. Ten different lectins, which exhibit a wide range of carbohydrate-binding specificities, were examined for their abilities to enhance the efficiency of lipofection. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (units/microg protein) and % blue cells following X-Gal stain. Lipofectin supplemented with Griffonia simplicifolia-I (GS-I) yields largest enhancement of the lipofection efficiency in A549 and Calu3 cells (5.3- and 28-fold, respectively). Maackia amurensis gives the largest enhancement (6.5-fold) of lipofection efficiency in H292 cells. The transfection efficiency correlates with the amounts of DNA delivered to the nucleus. Binding of FITC-labeled GS-I and the enhancement of the lipofection efficiency by GS-I were inhibited by alpha-methyl-D-galactopyranoside, indicating an alpha-galactoside-mediated gene transfer to lung carcinoma cells. We conclude that lectin-facilitated lipofection is an efficient gene delivery strategy. Employment of cell type-specific lectins may allow for efficient cell type-specific gene targeting.