A case of leptospirosis simulating colon cancer with liver metastases

PubMed Central

Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

2004-01-01

We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

[A Case of Chemotherapy with FOLFOXIRI plus Cetuximab for Liver Metastasis of Sigmoid ColonCan cer].

PubMed

Saito, Akina; Konishi, Ken; Fukunaga, Mutsumi; Takiguchi, Nobuo; Nakai, Shigeto; Honda, Shoko; Yukimoto, Ryohei; Okamoto, Aoi; Takeoka, Tomohira; Matsuno, Hiroshi; Okada, Kazuyuki; Ota, Hideo; Yokoyama, Shigekazu; Konishi, Muneharu; Kobayashi, Kenji

2018-03-01

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

Fungal colonization of the esophagus in alcoholic liver disease.

PubMed

Péter, Z; Zala, J; Szabó, O; Telegdy, L; Horváth, Z; Makara, M; Schuller, J

2000-10-01

Little is known about the fungal colonization of the esophagus. Since alcoholic liver disease (ALD) patients are prone to fungal esophagitis, we have investigated the esophageal fungal colonization of this patient group. One hundred consecutive ALD patients were enrolled in this prospective study. 22 patients with dyspeptic symptoms acted as controls. After taking an oropharyngeal swab, patients underwent an upper gastrointestinal endoscopy and surface material was obtained from the esophagus for direct smears and culture. In the ALD group pseudohyphae were found in 21.5% and yeast forms in 6.4% of the direct smears. The culture was positive in 40.8% of the ALD patients, the isolated strains were: 30 C. albicans, 2 C. kefyr, 2 C. krusei, 1 C. zeylanoides and in 3 cases the species could not be identified. 41.9% of ALD patients and 13.6% of control patients (p = 0.013) had fungi in their esophagus. Significantly more ALD patients had fungal esophagitis than in the control group (19.3% vs. 0%, p = 0.021), the rate of fungal colonization was also higher, but the difference was not significant (22.5% vs. 13.6%). A significantly higher rate of fungal esophagitis and esophageal colonization was found in patients with fungi in their oropharyngeal swabs (p = 0.00001). Fungal colonization of the esophagus is frequent in ALD patients. Its presence might have clinical significance in the case of liver transplantation.

Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

NASA Astrophysics Data System (ADS)

Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

1995-03-01

The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

[Surgical treatment of pulmonary metastases from colon and rectal cancer].

PubMed

Togashi, Ken-ichi; Aoki, K; Hirahara, H; Sugawara, M; Oguma, F

2004-09-01

We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.

Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model.

PubMed

Wang, Huan; Wu, Xia; Lezmi, Stephane; Li, Qian; Helferich, William G; Xu, Yueqing; Chen, Hong

2017-12-02

Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various bioactive compounds and it exerts beneficial effects including improvements in brain function and reduced risk of cardiovascular diseases. On the other hand, increased risk of thyroid and liver cancers by EGb have been reported in animals. A colon cancer metastasis model was established using intrasplenic injection of a human colon cancer cell line, SW620-luc in athymic mice to investigate the potential impact of EGb on colon cancer progression. After tumor establishment, EGb was intraperitonically injected daily for 5 wks. EGb significantly increased the rate of metastasis in mouse liver and decreased the number of necrotic and apoptotic cells in the metastatic liver when compared to the control. Meanwhile, EGb significantly induced proliferation of tumor cells in the metastatic liver, indicated by increased staining of Ki67 and H3S10p. mRNA expression of genes involved in cell cycle, metastasis, apoptosis, and oxidative stress were altered by EGb treatment in livers with tumors. Moreover, EGb activated the stress-responsive MAPK pathways in the liver with metastatic tumors. EGb exacerbated liver metastasis in a mouse colon cancer metastasis model. This is potentially due to the increased tumor cell proliferation involving stimulated MAPK pathways.

Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

ClinicalTrials.gov

2015-09-10

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

PubMed

Rayes, Roni F; Milette, Simon; Fernandez, Maria Celia; Ham, Boram; Wang, Ni; Bourdeau, France; Perrino, Stephanie; Yakar, Shoshana; Brodt, Pnina

2018-03-20

The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

A solid organising cryptogenic liver abscess and its association with a colonic tubullovillous adenoma

PubMed Central

Tan, Christopher B; Shah, Mitanshu; Rajan, Dhyan; Lipka, Seth; Ahmed, Shadab; Freedman, Lester; Rizvon, Kaleem; Mustacchia, Paul

2012-01-01

Cryptogenic liver abscess (CLA) is a well-known disease entity that has puzzled clinicians for centuries. With the advancement of diagnostic modalities, comes the decreasing incidence of liver abscess labelled as ‘cryptogenic’ in nature. Colonic diseases have been identified as a possible underlying condition found in patients with liver abscesses. Although rare, tubullovillous adenomas have been implicated as one of the colonic causes of a CLA. We present a case of a CLA in a 53-year-old man with a potentially associated tubullovillous adenoma found via colonoscopy. PMID:22778477

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney.

PubMed

Scheuher, Cynthia

2016-01-01

Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed.

Infections in liver and lung transplant recipients: a national prospective cohort.

PubMed

Gagliotti, Carlo; Morsillo, Filomena; Moro, Maria Luisa; Masiero, Lucia; Procaccio, Francesco; Vespasiano, Francesca; Pantosti, Annalisa; Monaco, Monica; Errico, Giulia; Ricci, Andrea; Grossi, Paolo; Nanni Costa, Alessandro

2018-03-01

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients' characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

PubMed

Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

2015-11-01

Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function.

[Liver and lung metastases of colorectal cancer. Long-term survival and prognostic factors].

PubMed

Sponholz, S; Bölükbas, S; Schirren, M; Oguzhan, S; Kudelin, N; Schirren, J

2016-02-01

The resection of liver and lung metastases from colorectal cancer has not yet been completely investigated. The aim of this study was to investigate the overall survival and prognostic factors for patients with liver and lung metastases from colorectal cancer. A retrospective review of a prospective database of 52 patients with liver and lung metastases from colorectal cancer, undergoing metastasectomy with curative intent from 1999-2009 at a single institution was carried out. The mean overall survival (OS) was 64 months. For synchronous liver and lung metastases the mean overall survival was 63 months (5-year survival 54 %) and for metachronous liver and lung metastases 74 months (5-year survival 58 %, p = 0.451). A poor prognostic outcome was observed in cases of localization of the primary tumor in the rectum (OS 81 vs. 38 months, p = 0.004), with multiple lung metastases (≥ 2 metastases, OS 74 vs. 59 months, p = 0.032) and with disease progression after premetastasectomy chemotherapy (OS 74 vs. 63 vs. 15 months, p < 0.001). No influence on overall survival was detected for bilateral lung metastases, thoracic lymph node metastases, disease recurrence and disease-free interval < 36 months. Metastasectomy for liver and lung metastases of colorectal cancer is associated with a good overall survival in selected cases. Patients with liver and lung metastases should not be routinely excluded from metastasectomy and patients with thoracic lymph node metastases should also not be routinely excluded. Negative prognostic factors for survival are localization of the tumor in the rectum, multiple metastases and disease progression after premetastasectomy chemotherapy. Patients with disease progression after premetastasectomy chemotherapy should be excluded from metastasectomy.

In vivo tomographic imaging of lung colonization of tumour in mouse with simultaneous fluorescence and X-ray CT.

PubMed

Zhang, Bin; Gao, Fuping; Wang, Mengjiao; Cao, Xu; Liu, Fei; Wang, Xin; Luo, Jianwen; Wang, Guangzhi; Bai, Jing

2014-01-01

Non-invasive in vivo imaging of diffuse and wide-spread colonization within the lungs, rather than distinct solid primary tumors, is still a challenging work. In this work, a lung colonization mouse model bearing A549 human lung tumor was simultaneously scanned by a dual-modality fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) system in vivo. A two steps method which incorporates CT structural information into the FMT reconstruction procedure is employed to provide concurrent anatomical and functional information. By using the target-specific fluorescence agent, the fluorescence tomographic results show elevated fluorescence intensity deep within the lungs which is colonized with diffuse and wide-spread tumors. The results were confirmed with ex vivo fluorescence reflectance imaging and histological examination of the lung tissues. With FMT reconstruction combined with the CT information, the dual-modality FMT/micro-CT system is expected to offer sensitive and noninvasive imaging of diffuse tumor colonization within the lungs in vivo. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

PubMed

Herrera, Sabina; Husain, Shahid

2018-05-21

The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy.

PubMed

Carpagnano, Giovanna E; Lacedonia, Donato; Palladino, Grazia Pia; Logrieco, Giuseppe; Crisetti, Elisabetta; Susca, Antonia; Logrieco, Antonio; Foschino-Barbaro, Maria P

2014-02-18

Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.

[Preoperatiove Airway Bacterial Colonization: the Missing Link between Non-small Cell Lung Cancer Following Lobectomy and Postoperative Pneumonia?

PubMed

Gao, Ke; Lai, Yutian; Huang, Jian; Wang, Yifan; Wang, Xiaowei; Che, Guowei

2017-04-20

Surgical procedure is the main method of treating lung cancer. Meanwhile, postoperative pneumonia (POP) is the major cause of perioperative mortality in lung cancer surgery. The preoperative pathogenic airway bacterial colonization is an independent risk factor causing postoperative pulmonary complications (PPC). This cross-sectional study aimed to explore the relationship between preoperative pathogenic airway bacterial colonization and POP in lung cancer and to identify the high-risk factors of preoperative pathogenic airway bacterial colonization. A total of 125 patients with non-small cell lung cancer (NSCLC) underwent thoracic surgery in six hospitals of Chengdu between May 2015 and January 2016. Preoperative pathogenic airway bacterial colonization was detected in all patients via fiber bronchoscopy. Patients' PPC, high-risk factors, clinical characteristics, and the serum surfactant protein D (SP-D) level were also analyzed. The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients was 15.2% (19/125). Up to 22 strains were identified in the colonization positive group, with Gram-negative bacteria being dominant (86.36%, 19/22). High-risk factors of pathogenic airway bacterial colonization were age (≥75 yr) and smoking index (≥400 cigarettes/year). PPC incidence was significantly higher in the colonization-positive group (42.11%, 8/19) than that in the colonization-negative group (16.04%, 17/106)(P=0.021). POP incidence was significantly higher in the colonization-positive group (26.32%, 5/19) than that in the colonization-negative group (6.60%, 7/106)(P=0.019). The serum SP-D level of patients in the colonization-positive group was remarkably higher than that in the colonization-negative group [(31.25±6.09) vs (28.17±5.23)](P=0.023). The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients with POP was 41.67% (5/12). This value was 3.4 times higher than that among the patients without

Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury

PubMed Central

van der Heijden, Karin M.; van der Heijden, Inneke M.; Galvao, Flavio H.; Lopes, Camila G.; Costa, Silvia F.; Abdala, Edson; D’Albuquerque, Luiz A.; Levin, Anna S.

2014-01-01

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups

Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non–Small Cell Lung Cancer Cells

PubMed Central

He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian

2016-01-01

Non–small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non–small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non–small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle–associated proteins by Western blot analysis and found immature colon carcinoma transcript 1–mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non–small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non–small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non–small cell lung cancer. PMID:27413166

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

PubMed

Bu, Pengcheng; Chen, Kai-Yuan; Xiang, Kun; Johnson, Christelle; Crown, Scott B; Rakhilin, Nikolai; Ai, Yiwei; Wang, Lihua; Xi, Rui; Astapova, Inna; Han, Yan; Li, Jiahe; Barth, Bradley B; Lu, Min; Gao, Ziyang; Mines, Robert; Zhang, Liwen; Herman, Mark; Hsu, David; Zhang, Guo-Fang; Shen, Xiling

2018-06-05

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth. Copyright © 2018 Elsevier Inc. All rights reserved.

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir

2014-08-15

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractionsmore » from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.« less

Metastatic Male Ductal Breast Cancer Mimicking Obstructing Primary Colon Cancer

PubMed Central

Koleilat, Issam; Syal, Anil; Hena, Muhammad

2010-01-01

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy

PubMed Central

2014-01-01

Background Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. Methods We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. Results For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. Conclusion The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy. PMID:24548615

EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-15

Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

Epithelioid hemangioendotheliomas of the liver and lung in children and adolescents.

PubMed

Hettmer, Simone; Andrieux, Geoffroy; Hochrein, Jochen; Kurz, Philipp; Rössler, Jochen; Lassmann, Silke; Werner, Martin; von Bubnoff, Nikolas; Peters, Christoph; Koscielniak, Ewa; Sparber-Sauer, Monika; Niemeyer, Charlotte; Mentzel, Thomas; Busch, Hauke; Boerries, Melanie

2017-12-01

Epithelioid hemangioendothelioma (EHE) is a rare, vascular sarcoma. Visceral forms arise in the liver/ lungs. We review the clinical and molecular phenotype of pediatric visceral EHE based on the case of a 9-year-old male child with EHE of the liver/lungs. His tumor expressed the EHE-specific fusion oncogene WWTR1-CAMTA1. Molecular characterization revealed a low somatic mutation rate and activated interferon signaling, angiogenesis regulation, and blood vessel remodeling. After polychemotherapy and resection of lung tumors, residual disease remained stable on oral lenalidomide. Literature review identified another 24 children with EHE of the liver/lungs. Most presented with multifocal, systemic disease. Only those who underwent complete resection achieved complete remission. Four children experienced rapid progression and died. In six children, disease remained stable for years without therapy. Two patients died from progressive EHE 21 and 24 years after first diagnosis. Natural evolution of pediatric visceral EHE is variable, and long-term prognosis remains unclear. © 2017 Wiley Periodicals, Inc.

Independent predictors of morbidity and mortality in blunt colon trauma.

PubMed

Ricciardi, R; Paterson, C A; Islam, S; Sweeney, W B; Baker, S P; Counihan, T C

2004-01-01

We sought to determine the impact of (1) grade of the colon injury, (2) the formation of an ostomy, and (3) associated injuries on outcomes such as morbidity and mortality after blunt colon injuries. We retrospectively reviewed 16,814 cases of blunt abdominal trauma. Patients with colonic injuries were selected and charts reviewed for demographic, clinical, and outcomes data. Injuries were grouped by the Colon Injury Scale (grades I-V). Independent risk factors of morbidity included spine and lung injuries, as well as increased age. A higher grade of colon injury trended toward a significant association with intra-abdominal complications. Independent risk factors of mortality included liver, heart, and lung injuries, as well as intracerebral blood and female gender. The grade of colon injury, the formation of an ostomy, and management of the colon trauma did not independently predict increased intra-abdominal complications, morbidity, or mortality. These results indicate that patients afflicted with blunt colon trauma experience a high rate of morbidity and mortality from associated injuries and or increased age. Treatment regimens directed at these factors will be most helpful in reducing the high morbidity and mortality after blunt colon trauma. Factors such as ostomy formation and management strategy are not associated with increased morbidity or mortality after blunt colon trauma.

Pretransplant Aspergillus colonization of cystic fibrosis patients and the incidence of post-lung transplant invasive aspergillosis.

PubMed

Luong, Me-Linh; Chaparro, Cecilia; Stephenson, Anne; Rotstein, Coleman; Singer, Lianne G; Waters, Valerie; Azad, Sassan; Keshavjee, Shaf; Tullis, Elizabeth; Husain, Shahid

2014-02-15

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among patients undergoing lung transplant. Cystic fibrosis-lung transplant recipients (CF-LTRs) may be at greater risk of IA following lung transplantation because of the presence of Aspergillus in their airways before transplantation. This study evaluated the impact of pretransplant Aspergillus colonization on the risk for IA among CF-LTRs. A single-center retrospective cohort study of CF-LTRs was conducted between 2006 and 2010. Respiratory tract cultures before transplantation were reviewed to identify patients with pretransplant Aspergillus colonization. Patients with positive Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL) galactomannan after transplantation were classified as having colonization or disease according to the International Society of Heart and Lung Transplantation criteria. A total of 93 CF patients underwent lung transplantation. Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization. Thirty-six patients had positive intraoperative Aspergillus culture from the native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to IA was 42 days following transplantation. Positive intraoperative Aspergillus culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15, P=0.05) were independent risk factors for IA. Antifungal prophylaxis was administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93). IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06, P=0.23). Pretransplant Aspergillus colonization is frequent among CF-LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher risk of developing IA.

Comparison of radiography and ultrasonography in the detection of lung and liver cysts in cattle and buffaloes

PubMed Central

Kumar, Ashwani; Saini, Narinder Singh; Mohindroo, Jitender; Singh, Balbir Bagicha; Sangwan, Vandana; Sood, Naresh Kumar

2016-01-01

Aim: Echinococcosis is the major cause of lung and liver cysts in ruminants. This study compared usefulness of radiography and ultrasonography (USG) in the detection of lung and/or liver cysts in sick bovine animals. The study also worked out cooccurrence of lung and liver cysts, and whether these cysts were primary cause of sickness or not. Materials and Methods: This study was conducted on 45 sick bovine (37 buffaloes and 8 cattle) suffering from lung and liver cysts. A complete history of illness and clinical examination was carried out. Lateral radiographs of chest and reticular region were taken. In radiographically positive or suspected cases of cysts, USG of the lung and liver region was done. Depending on the location of cyst and clinical manifestations of the animal, the cysts were categorized as primary or secondary causes of sickness. Results: Using either imaging technique, it was observed that 46.7% of the animals had both lung and liver cysts, whereas 33.3% had only lung and 20% had only liver cyst. Cysts were identified as primary cause of sickness in 31.1% animals only. For diagnosing lung cysts, radiography (71.1%) and USG (62.2%) had similar diagnostic utility. However, for detecting liver cysts, USG was the only imaging tool. Conclusion: The lung and liver cysts, depending on their number and size may be a primary cause of sickness in bovine. Radiography and USG are recommended, in combination, as screening tools to rule out echinococcosis. PMID:27847421

Evaluation of Lung Function in Liver Transplant Candidates.

PubMed

Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

2018-04-01

A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

Lower incidence of bronchiolitis obliterans in pediatric liver-lung transplant recipients with cystic fibrosis.

PubMed

Faro, Albert; Shepherd, Ross; Huddleston, Charles B; Lowell, Jeffrey; Gandhi, Sanjiv; Nadler, Michelle; Sweet, Stuart C

2007-06-15

Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution. We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection. Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025). Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.

The lung in liver disease: old problem, new concepts.

PubMed

Fallon, Michael B; Zhang, Junlan

2013-01-01

Liver dysfunction has been recognized to influence the lung in many different clinical situations, although the mechanisms for these effects are not well understood. One increasingly recognized interaction, the hepatopulmonary syndrome (HPS) occurs in the context of cirrhosis and results when alveolar microvascular dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in up to 30% of patients with cirrhosis and significantly increases mortality in affected patients. Currently, liver transplantation is the only curative therapy. Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and has been contrasted with other experimental models of cirrhosis in which HPS does not develop. Microvascular dilation, intravascular monocyte infiltration, and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Our recent studies have identified biliary epithelium and activation and interaction between the endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1 pathways as important mechanisms for the observed pathologic events. These studies define novel interactions between the lung and liver in cirrhosis and may lead to effective medical therapies.

Reactive Lymphoid Hyperplasia of the liver in a patient with colon cancer: report of two cases

PubMed Central

Takahashi, Hiroki; Sawai, Hirozumi; Matsuo, Yoichi; Funahashi, Hitoshi; Satoh, Mikinori; Okada, Yuji; Inagaki, Hiroshi; Takeyama, Hiromitsu; Manabe, Tadao

2006-01-01

Background Reactive lymphoid hyperplasia (RLH) of the liver is very rarely reported, and we encountered two cases of RLH of the liver in a patient with colon cancer. Case presentation In the first case, a 77-year-old woman was admitted for the surgical removal of a ascending colon cancer. A hepatic tumor in the left lobe was concurrently revealed by computed tomography (CT), and magnetic resonance imaging (MRI). The appearance suggested liver metastasis. Right hemicolectomy and partial hepatectomy were performed. On histopathological examination, lymphoid follicles with germinal centers were seen in the tumor-like lesion, and remarkable lymphoid infiltration with germinal centers was seen in the portal area around the nodule. Immunohistochemical studies revealed polyclonality of infiltrating lymphocyte. Consequently, this nodular lesion was diagnosed as RLH of the liver. In the second case, a 64-year-old woman who had a radical right hemicolectomy for stage II ascending colon cancer 10 years ago was admitted with dysuria. A hepatic tumor in the left lobe was concurrently revealed by CT and MRI, suggesting hepatocellular carcinoma. A left lateral segmentectomy was performed. Microscopically, this lesion revealed the almost same findings as the first case, so this nodular lesion was diagnosed as RLH of the liver. Conclusion Our two cases were the first report of RLH of the liver accompanying colon cancer. Because there are a very few cases, so it is not clear whether the malignancies were involved in the onset of RLH. But we believe that new factors involved in the onset mechanism of RLH may be identified by carefully monitoring the clinical course of our two patients. PMID:16965640

Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

ClinicalTrials.gov

2018-02-22

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

PubMed Central

Liu, Yuan; Wang, Xin-Yue; Yang, Xue; Jing, Shan; Zhu, Li; Gao, Si-Hua

2013-01-01

Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC) rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A) in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage. PMID:23606829

Genetic relationship between the Echinococcus granulosus sensu stricto cysts located in lung and liver of hosts.

PubMed

Oudni-M'rad, Myriam; Cabaret, Jacques; M'rad, Selim; Chaâbane-Banaoues, Raja; Mekki, Mongi; Zmantar, Sofien; Nouri, Abdellatif; Mezhoud, Habib; Babba, Hamouda

2016-10-01

G1 genotype of Echinococcus granulosus sensu stricto is the major cause of hydatidosis in Northern Africa, Tunisia included. The genetic relationship between lung and liver localization were studied in ovine, bovine and human hydatid cysts in Tunisia. Allozyme variation and single strand conformation polymorphism were used for genetic differentiation. The first cause of genetic differentiation was the host species and the second was the localization (lung or liver). The reticulated genetic relationship between the liver or the lung human isolates and isolates from bovine lung, is indicative of recombination (sexual reproduction) or lateral genetic transfer. The idea of two specialized populations (one for the lung one for the liver) that are more or less successful according to host susceptibility is thus proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

PubMed

Ateyya, Hayam; Nader, Manar A; Attia, Ghalia M; El-Sherbeeny, Nagla A

2017-05-01

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft.

PubMed

Weigt, S Samuel; Wang, Xiaoyan; Palchevskiy, Vyacheslav; Patel, Naman; Derhovanessian, Ariss; Shino, Michael Y; Sayah, David M; Lynch, Joseph P; Saggar, Rajan; Ross, David J; Kubak, Bernie M; Ardehali, Abbas; Palmer, Scott; Husain, Shahid; Belperio, John A

2018-06-01

Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis. We examined transcriptional profiles in 3- or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with Aspergillus fumigatus colonization (n = 12) and without colonization (n = 10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n = 6) or remained CLAD-free (n = 6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression was based on an absolute fold difference of 2.0 or greater and unadjusted P value less than 0.05. We used NIH Database for Annotation, Visualization and Integrated Discovery for functional analyses, with false discovery rates less than 5% considered significant. Aspergillus colonization was associated with differential expression of 489 probe sets, representing 404 unique genes. "Defense response" genes and genes in the "cytokine-cytokine receptor" Kyoto Encyclopedia of Genes and Genomes pathway were notably enriched in this list. Among Aspergillus colonized patients, CLAD development was associated with differential expression of 69 probe sets, representing 64 unique genes. This list was enriched for genes involved in "immune response" and "response to wounding", among others. Notably, both chitinase 3-like-1 and chitotriosidase were associated with progression to CLAD. Aspergillus colonization is associated with gene expression profiles related to defense responses including cytokine signaling. Epithelial wounding, as well as the innate immune response to chitin that is present in the fungal cell wall, may be key in the link between Aspergillus colonization and CLAD.

[One staged laparoscopic surgery of colon cancer with liver metastasis in the Guillermo Almenara Hospital, Lima, Peru].

PubMed

Núñez Ju, Juan José; Coronado3, Cesar Carlos; Anchante Castillo, Eduardo; Sandoval Jauregui, Javier; Arenas Gamio, José

2016-01-01

We report a patient who was diagnosed sigmoid colon cancer associated with liver metastases in segment III. The patient underwent laparoscopic surgery where the sigmoid colon resection and hepatic metastasectomy were performed in a “one staged” surgical procedure. The pathological results showed moderately differentiated tubular adenocarcinoma in sigmoid colon, tubular adenocarcinoma metastases also in liver. Oncological surgical results were obtained with free edges of neoplasia, R0 Surgery, T3N0M1. After the optimal surgical results, the patient is handled by oncology for adjuvant treatment. We report here the sequence of events and a review of the literature.

Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

PubMed

da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; Dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

2015-01-01

Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.

PubMed

Ren, Yijiu; Dai, Chenyang; Zheng, Hui; Zhou, Fangyu; She, Yunlang; Jiang, Gening; Fei, Ke; Yang, Ping; Xie, Dong; Chen, Chang

2016-08-16

Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.

Clinical Validation of Targeted Next Generation Sequencing for Colon and Lung Cancers

PubMed Central

D’Haene, Nicky; Le Mercier, Marie; De Nève, Nancy; Blanchard, Oriane; Delaunoy, Mélanie; El Housni, Hakim; Dessars, Barbara; Heimann, Pierre; Remmelink, Myriam; Demetter, Pieter; Tejpar, Sabine; Salmon, Isabelle

2015-01-01

Objective Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. Methods We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF). Then, 51 colorectal adenocarcinomas (CRC) and 39 non small cell lung carcinomas (NSCLC) were retrospectively analyzed. Results Sensitivity and accuracy for detecting variants at an AF >4% was 100% for commercial reference standards. Among the 90 cases, 89 (98.9%) were successfully sequenced. Among the 86 samples for which NGS and the reference test were both informative, 83 showed concordant results between NGS and the reference test; i.e. KRAS and BRAF for CRC and EGFR for NSCLC, with the 3 discordant cases each characterized by an AF <10%. Conclusions Overall, the AmpliSeq colon/lung cancer panel was specific and sensitive for mutation analysis of gene panels and can be incorporated into clinical daily practice. PMID:26366557

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Hilmersson, Katarzyna Said; Andersson, Roland

2018-01-01

To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

PubMed

Corno, V; Dezza, M C; Lucianetti, A; Codazzi, D; Carrara, B; Pinelli, D; Parigi, P C; Guizzetti, M; Strazzabosco, M; Melzi, M L; Gaffuri, G; Sonzogni, V; Rossi, A; Fagiuoli, S; Colledan, M

2007-10-01

Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

Unusual metastasis of left colon cancer: considerations on two cases.

PubMed

Gubitosi, Adelmo; Moccia, Giancarlo; Malinconico, Francesca Antonella; Gilio, Francesco; Iside, Giovanni; Califano, Umberto G A; Foroni, Fabrizio; Ruggiero, Roberto; Docimo, Giovanni; Parmeggiani, Domenico; Agresti, Massimo

2009-04-01

Usually, left colon cancer metastasis concerns liver, abdominal lymph nodes and lungs. Other localizations are quite rare occurrences. In spite of this, some uncommon metastasis sites are reported in literature, such as: peritoneum, ovaries, uterus, kidney testis, bones, thyroid, oral cavity and central nervous system. We report two cases of unusual localizations of left colon cancer metastasis localization, one into the retroperitoneal space and the other at the left axillary lynphnodes and between liver and pancreas. In the first reported case the diffusion pathway may have been the lymphatic mesocolic vessels, partially left in place from the previous surgery. In the second case the alleged metastatic lane may have been through the periumbilical lymph nodes to the parasternal lymph nodes and then to the internal mammary ones, finally reaching the axillary limph nodes.

E phage gene transfection associated to chemotherapeutic agents increases apoptosis in lung and colon cancer cells.

PubMed

Rama, Ana R; Prados, Jose; Melguizo, Consolacion; Alvarez, Pablo J; Ortiz, Raúl; Madeddu, Roberto; Aranega, Antonia

2011-01-01

The limited ability of conventional therapies to achieve the long-term survival of metastatic lung and colon cancer patients suggests the need for new treatment options. In this respect, genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the activity of drugs, and combined therapies involving such genes and classical antitumoral drugs have been studied intensively. The E gene from phiX174 encodes a membrane protein with a toxic domain that leads to a decrease in tumour cell growth rates. Therefore, in order to improve the anti-tumour effects of currently used chemotherapeutic drugs on cancer cells, we investigated the association of the E suicide gene with these antineoplastic drugs. The E gene has antitumoral effects in both lung and colon cancer cells. In addition, expression of this gene induces ultrastructural changes in lung cancer transfected cells (A-549), although the significance of these changes remains unknown. The effect of combined therapy (gene and cytotoxic therapy) enhances the inhibition of tumour cell proliferation in comparison to single treatments. Indeed, our in vitro results indicate that an experimental therapeutic strategy based on this combination of E gene therapy and cytotoxic drugs may result in a new treatment strategy for patients with advanced lung and colon cancer.

Ectopic fascioliasis mimicking a colon tumor

PubMed Central

Makay, Ozer; Gurcu, Baris; Caliskan, Cemil; Nart, Deniz; Tuncyurek, Muge; Korkut, Mustafa

2007-01-01

Fasciola hepatica, a leaf shaped trematode that is common in cattle, sheep and goats, is acquired by eating raw water plants like watercress or drinking water infected with the encysted form of the parasite. The varied clinical presentations of fascioliasis still make a high index of suspicion mandatory. Besides having a wide spectrum of hepatobiliary symptoms like obstructive jaundice, cholangitis and liver cirrhosis, the parasitic infection also has extrabiliary manifestations. Until recently, extrahepatic fascioliasis has been reported in the subcutaneous tissue, brain, lungs, epididymis, inguinal lymph nodes, stomach and the cecum. In this report, a strange manifestation of the fasciola infection in a site other than the liver, a colonic fascioliasis, is presented. PMID:17552017

Potential Role of the Gut/Liver/Lung Axis in Alcohol-Induced Tissue Pathology

PubMed Central

Massey, Veronica L.; Beier, Juliane I.; Ritzenthaler, Jeffrey D.; Roman, Jesse; Arteel, Gavin E.

2015-01-01

Both Alcoholic Liver Disease (ALD) and alcohol-related susceptibility to acute lung injury are estimated to account for the highest morbidity and mortality related to chronic alcohol abuse and, thus, represent a focus of intense investigation. In general, alcohol-induced derangements to both organs are considered to be independent and are often evaluated separately. However, the liver and lung share many general responses to damage, and specific responses to alcohol exposure. For example, both organs possess resident macrophages that play key roles in mediating the immune/inflammatory response. Additionally, alcohol-induced damage to both organs appears to involve oxidative stress that favors tissue injury. Another mechanism that appears to be shared between the organs is that inflammatory injury to both organs is enhanced by alcohol exposure. Lastly, altered extracellular matrix (ECM) deposition appears to be a key step in disease progression in both organs. Indeed, recent studies suggest that early subtle changes in the ECM may predispose the target organ to an inflammatory insult. The purpose of this chapter is to review the parallel mechanisms of liver and lung injury in response to alcohol consumption. This chapter will also explore the potential that these mechanisms are interdependent, as part of a gut-liver-lung axis. PMID:26437442

A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.

PubMed

Choi, Jin-A; Jeong, Yu-Jin; Kim, Jae-Eun; Kang, Min-Jung; Kim, Jee-Cheon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Hyun; Kim, Dong-Jae; Park, Jong-Hwan

2016-02-01

Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.

2015-07-15

Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5more » fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a

High dietary intake of sodium selenite does not affect gene mutation frequency in rat colon and liver.

PubMed

Zeng, Huawei; Uthus, Eric O; Ross, Sharon A; Davis, Cindy D

2009-10-01

Our previous studies have shown that selenium (Se) is protective against dimethylhydrazine (DMH)-induced preneoplastic colon cancer lesions, and protection against DNA damage has been hypothesized to be one mechanism for the anticancer effect of Se. The present study was designed to determine whether dietary selenite affects somatic mutation frequency in vivo. We used the Big Blue transgenic model to evaluate the in vivo mutation frequency of the cII gene in rats fed either a Se-deficient (0 microg Se/g diet) or Se-supplemented diet (0.2 or 2 microg Se/g diet; n = 3 rats/diet in experiment 1 and n = 5 rats/group in experiment 2) and injected with DMH (25 mg/kg body weight, i.p.). There were no significant differences in body weight between the Se-deficient and Se-supplemented (0.2 or 2 microg Se/g diet) rats, but the activities of liver glutathione peroxidase and thioredoxin reductase and concentration of liver Se were significantly lower (p < 0.0001) in Se-deficient rats compared to rats supplemented with Se. We found no effect of dietary Se on liver 8-hydroxy-2'-deoxyguanosine. Gene mutation frequency was significantly lower in liver (p < 0.001) than that of colon regardless of dietary Se. However, there were no differences in gene mutation frequency in DNA from colon mucosa or liver from rats fed the Se-deficient diet compared to those fed the Se-supplemented (0.2 or 2 microg Se/g diet) diet. Although gene mutations have been implicated in the etiology of cancer, our data suggest that decreasing gene mutation is not likely a key mechanism through which dietary selenite exerts its anticancer action against DMH-induced preneoplastic colon cancer lesions in a Big Blue transgenic rat model.

Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

PubMed

Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

2012-05-01

3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis

PubMed Central

Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L.; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J.; Rafii, Shahin; Ding, Bi-Sen

2017-01-01

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. Here, we show that targeting both the vascular niche and perivascular fibroblasts establishes “hospitable soil” to foster incorporation of “seed”, in this case the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NADPH Oxidase 4 (NOX4) synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs (HgfiΔEC/iΔEC) aberrantly upregulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially-inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in HgfiΔEC/iΔEC mice recapitulated the phenotype of human and mouse fibrotic livers and lungs. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. PMID:28855398

Gastroesphageal Variceal Hemorrhage Induced by Metastatic Liver Tumor of Lung Cancer

PubMed Central

Honda, Takayuki; Kobayashi, Hiroaki; Saiki, Masafumi; Sogami, Yusuke; Miyashita, Yoshihiro; Inase, Naohiko

2012-01-01

Gastroesophageal variceal hemorrhage is a lethal complication of portal hypertension. Liver cirrhosis is often the principal cause of the portal hypertensive state. Malignant tumors coexist with portal hypertension in some cases. Non-small-cell lung cancer (NSCLC) is likely to become metastatic. Liver is a frequent site of cancer metastasis, but diffuse hepatic sinusoidal metastasis is uncommon as a metastatic form of NSCLC. This report describes a patient with gastroesophageal variceal hemorrhage owing to a metastatic liver tumor of NSCLC. The patient, a male smoker with stage IV NSCLC, was free of any hepatitis viral infection and had no alcohol addiction. Liver dysfunction and liver disease had never been pointed out in his medical history. His tumor harbored an L858R epidermal growth factor receptor mutation. Gefitinib was initiated but had to be ceased because of interstitial lung disease. Sequential steroid therapy was effective and bevacizumab-containing chemotherapy was commenced. Both chemotherapy regimens produced favorable effects against the metastatic liver tumor, eliciting atrophic change regardless of the chemotherapy-free interval. One day the patient was admitted to our hospital because of black stool and hypotension. Upper gastrointestinal endoscopy revealed a beaded appearance of the gastroesophageal varix with bloody gastric contents. The portal hypertension might have been caused by changes in portal vein hemodynamics induced by the conformational changes underlying the favorable response of the liver tumor to molecular targeted chemotherapy and notable regression. PMID:23275780

Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche.

PubMed

Aguado, Brian A; Caffe, Jordan R; Nanavati, Dhaval; Rao, Shreyas S; Bushnell, Grace G; Azarin, Samira M; Shea, Lonnie D

2016-03-01

Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM-coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. The pre-metastatic niche consists partially of ECM proteins that promote metastatic cell colonization to a target organ. We present a biomaterials-based approach to mimic this niche and identify ECM mediators of colonization. Using murine breast cancer models, we implanted microporous PCL scaffolds to recruit colonizing tumor cells in vivo. As a strategy to modulate colonization, we coated scaffolds with various ECM proteins, including decellularized lung and liver matrix from

Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

PubMed

Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

2013-10-01

An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver.

PubMed

Meijer, Joost; Zeelenberg, Ingrid S; Sipos, Bence; Roos, Ed

2006-10-01

The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.

Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

PubMed

Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

2010-01-01

The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

The Effects of Lasiocarpine, Retrorsine and Retronecine Pyrrole on Human Embryo Lung and Liver Cells in Culture

PubMed Central

Armstrong, Sylvia J.; Zuckerman, A. J.

1972-01-01

Retronecine pyrrole induces toxic changes both in human liver and lung cells. Lasiocarpine and retrorsine are toxic to liver cells but not to lung cells, which are unable to metabolize the pyrrolizidine alkaloids to pyrroles. The application of lasiocarpine to human liver cells in culture is followed by inhibition of DNA, RNA and protein synthesis; vacuolation of the cells, the prevention of mitosis and the formation of giant cells (“megalocytes”). PMID:5032089

Toxocariasis masquerading as liver and lung metastatic nodules in patents with gastrointestinal cancer: clinicopathologic study of five cases.

PubMed

Park, Sanghui; Kim, Yun Soo; Kim, Yu Jin; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Lee, Sang Pyo

2012-01-01

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.

PubMed

Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J; Rafii, Shahin; Ding, Bi-Sen

2017-08-30

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NOX4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 4] synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs ( Hgf iΔEC/iΔEC ) aberrantly up-regulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in Hgf iΔEC/iΔEC mice recapitulated the phenotype of human and mouse liver and lung fibrosis. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

PubMed

Hara, Y; Ogata, Y; Shirouzu, K

2000-12-01

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Percutaneous transhepatic drainage of lung abscess through a diaphragmatic fistula caused by a penetrating liver abscess.

PubMed

Taniguchi, Masako; Morita, Satoru; Ueno, Eiko; Hayashi, Mitsutoshi; Ishikawa, Motonao; Mae, Masahiro

2011-11-01

Liver abscesses occurring just below the diaphragm can penetrate or perforate the thoracic cavity, resulting in lung abscess or pyothorax. Although surgical or percutaneous transpleural drainage is often required in such cases, the latter approach has some risks, including hemothorax and bronchopleural fistula formation when the cavity is surrounded by normal lung parenchyma. The present report describes a treatment technique of percutaneous transhepatic drainage through the diaphragmatic fistula to avoid the risks of a transpulmonary approach in a case of lung abscess caused by a penetrating liver abscess.

Chronic Aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function.

PubMed

Saunders, Rosalind V; Modha, Deborah E; Claydon, Alison; Gaillard, Erol A

2016-07-01

Filamentous fungi are commonly isolated from the respiratory tract of CF patients, but their clinical significance is uncertain and the reported incidence variable. We report on the degree of Aspergillus fumigatus airway colonization in a tertiary pediatric CF cohort, evaluate the sensitivity of routine clinical sampling at detecting A. fumigatus, and compare lung function of A. fumigatus-colonized and non-colonized children.We carried out an 8-year retrospective cohort analysis using local databases, examining 1024 respiratory microbiological specimens from 45 children. Nineteen (42%) had a positive A. fumigatus culture at least once during the 8-year period, with 10 (22%) children persistently colonized. Overall, 29% of 48 bronchoalveolar lavage (BAL) samples tested positive for A. fumigatus, compared with 14% of 976 sputum samples. Of 33 children for whom lung function data were available during the study period, seven were classed as having severe lung disease, of whom four (57%) were persistently colonized with A. fumigatus.We conclude that chronic A. fumigatus colonization of the CF airway is common, and may be associated with worse lung function. In our practice, BAL appears superior at detecting lower airway A. fumigatus compared to sputum samples. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Folate supplementation differently affects uracil content in DNA in the mouse colon and liver

USDA-ARS?s Scientific Manuscript database

High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C5...

Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung.

PubMed

Yakubu, D P; Mostyn, A; Hyatt, M A; Kurlak, L O; Budge, H; Stephenson, T; Symonds, M E

2007-12-01

This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term approximately 147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.

Glutamine Supplementation Attenuates Ethanol-Induced Disruption of Apical Junctional Complexes in Colonic Epithelium and Ameliorates Gut Barrier Dysfunction and Fatty Liver in Mice

PubMed Central

Chaudhry, Kamaljit K.; Shukla, Pradeep K.; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E.; Rao, RadhaKrishna

2015-01-01

Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of glutamine in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed Gln-free diet and absent in mice fed Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

Metastasis of colon cancer to the thyroid gland: a case diagnosed on fine-needle aspirate by a combined cytological, immunocytochemical, and molecular approach.

PubMed

Cozzolino, Immacolata; Malapelle, Umberto; Carlomagno, Chiara; Palombini, Lucio; Troncone, Giancarlo

2010-12-01

Fine-needle aspiration (FNA) with cytological evaluation reliably diagnoses primary and secondary thyroid neoplasms. However, identifying the primary origin of a metastatic process involving the thyroid gland is challenging. In particular, metastasis of colon cancer to the thyroid gland is very rare. In this case report, a right lobe solid thyroid nodule in a 66-year-old male was aspirated. FNA cytology showed necrosis and atypical tall columnar cells; since, the patient at age 60 had undergone surgery for a sigmoid-rectal cancer metastasizing to the liver and subsequently to the lung, a suspicion of metastasis from colon cancer was raised. This was corroborated by cell-block immunocytochemistry showing a cytokeratin (CK) 7 negative/CK20-positive staining pattern; thyreoglobulin and TTF-1 were both negative. Since KRAS codon 12/13 mutations frequently occur in colon cancer, whereas they are extremely uncommon in primary thyroid tumors, DNA was extracted from the aspirated cells, and KRAS mutational analysis was carried out. The codon 12 G12D mutation was found; the same mutation was evident in the primary cancer of the colon and in its liver and lung metastasis. Thus, a combined cytological, immunocytochemical and molecular approach unquestionably correlated metastatic adenocarcinoma cells aspirated from the thyroid to a colo-rectal origin. © 2010 Wiley-Liss, Inc.

Lobular breast cancer metastasis to the colon, the appendix and the gallbladder.

PubMed

Molina-Barea, Rocio; Rios-Peregrina, Rosa M; Slim, Mahmoud; Calandre, Elena P; Hernández-García, Maria D; Jimenez-Rios, José A

2014-12-01

Metastases of lobular breast cancer are commonly encountered at the level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal tract are rarely seen. A case of a patient with metastases in the right colon and gallbladder originating from an invasive lobular carcinoma is described. Adequate diagnostic procedures should be performed in patients with a history of breast cancer and who show gastrointestinal symptoms to rule out the potential presence of gastrointestinal metastases.

Is Survival for Patients with Resectable Lung Metastatic Colorectal Cancer Comparable to Those with Resectable Liver Disease? Results from the South Australian Metastatic Colorectal Registry.

PubMed

Patel, Dainik; Townsend, Amanda R; Karapetis, Christos; Beeke, Carol; Padbury, Rob; Roy, Amitesh; Maddern, Guy; Roder, David; Price, Timothy J

2016-10-01

Hepatic resection for colorectal (CRC) metastasis is considered a standard of care. Resection of metastasis isolated to lung also is considered potentially curable, although there is still some variation in recommendations. We explore outcomes for patients undergoing lung resection for mCRC, with the liver resection group as the comparator. South Australian (SA) metastatic CRC registry data were analysed to assess patient characteristics and survival outcomes for patients suitable for lung or liver resection. A total of 3241 patients are registered on the database to December 2014. One hundred two (3.1 %) patients were able to undergo a lung resection compared with 420 (12.9 %) who had a liver resection. Of the lung resection patients, 62 (61 %) presented with lung disease only, 21 % initially presented with liver disease only, 11 % had both lung and liver, and 7 % had brain or pelvic disease resection. Of these patients, 79 % went straight to surgery without any neoadjuvant treatment and 34 % had lung resection as the only intervention. Chemotherapy for metastatic disease was given more often to liver resection patients: 76.9 versus 53.9 %, p = 0.17. Median overall survival is 5.6 years for liver resection and has not been reached for lung resection (hazard ratio 0.82, 95 % confidence interval 0.54-1.24, p = 0.33). Lung resection was undertaken in 3.1 % of patients with mCRC in our registry. These data provide further support for long-term survival after lung resection in mCRC, survival that is at least comparable to those who undergo resection for liver metastasis in mCRC.

[A case of unresectable colon cancer responding to oral leucovorin+oral tegafur/uracil].

PubMed

Saito, Naoto; Ohata, Masahiko; Ishii, Hiroshi; Ohori, Masaki; Tokura, Yasuyuki; Maruyama, Masanobu; Furukawa, Toshitaka; Sato, Hideaki

2007-08-01

The patient was a 63-year-old man,who first visited our hospital with the chief complaints of left lower quadrant pain and abdominal distension that had developed around November 13, 2004. On close examination, he was diagnosed with sigmoid colon cancer, multiple liver metastasis, and subileus due to a lung metastasis. His operation took place on December 12 of the same year. Intraoperatively, the sigmoid colon was firmly fixed to the retroperitonium, there was a hard node in the pouch of Douglas, and that part of the jejunum was involved. The lesion was judged to be unresectable,and thus loop colostomy, partial jejunectomy and gastrojejunostomy were performed. After the surgery,the patient was treated with 4 courses of therapy with oral Leucovorin (LV, 75 mg) +oral tegafur/uracil (UFT, 400 mg). As a result, the tumor marker levels decreased markedly, the lung metastasis was no longer observed and the liver metastases became smaller. Therefore, a second-look operation was performed on May 30, 2005. This time it was relatively easy to free the sigmoid colon. The node in the pouch of Douglas was no longer observed, and there were only 2 metastatic lesions in the liver (1 each in S 2 and S 6). Sigmoidectomy and partial hepatectomy were performed, and the stoma was closed. The patient made good progress after the operation and was discharged on the 11 th POD. At present he is receiving chemotherapy with UFT+oral LV as an outpatient. As this therapy is relatively easy to perform and imposes only a small burden on patients,we think that it may be effective not only as adjuvant chemotherapy but also as neoadjuvant chemotherapy in some patients.

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients

PubMed Central

Mansh, M.; Binstock, M.; Williams, K.; Hafeez, F.; Kim, J.; Glidden, D.; Boettger, R.; Hays, S.; Kukreja, J.; Golden, J.; Asgari, M.M.; Chin-Hong, P.; Singer, J.P.; Arron, S.

2015-01-01

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but has been associated with an increased risk for developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance its competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco transplanted between October 1991 and December 2012 (n=455) to investigate whether voriconazole exposure impacted development of SCC, Aspergillus colonization, invasive aspergillosis, and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk for developing SCC (HR=1.73; 95% CI: 1.04–2.88; p=0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR=1.03; 95% CI: 1.02–1.04; p<0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR=0.50; 95% CI: 0.34–0.72; p<0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR=0.34; 95% CI: 0.13–0.91; p=0.03), but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole in the care of lung transplant recipients. PMID:26372838

Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival.

PubMed

Pham, Phuong-Thu T; Slavov, Carmen; Pham, Phuong-Chi T

2009-07-01

Recipients of nonrenal organ transplants including the liver, heart, and lung are at risk for developing acute kidney injury (AKI) and chronic kidney disease (CKD). Underlying hepatic or cardiopulmonary failure, prolonged intraoperative hemodynamic instability, and the use of calcineurin inhibitors and nephrotoxic medications have all been suggested to be contributory. The incidence of perioperative AKI has been reported to occur in 17% to 95% in liver transplant recipients, 5% to 30% in heart transplant recipients, and 5% to 60% in recipients of lung transplants. Among those who develop AKI, renal replacement therapy is required in 5% to 35%, 5% to 15%, and 8% to 10% in liver, heart, and lung transplant recipients, respectively. The current article presents an overview of the literature on the choice of dialysis modality and its associated advantages and disadvantages in the management of AKI after liver, heart, and lung transplants. Predictive factors for renal function recovery and the impact of AKI and CKD on survival will also be discussed.

Malignant tumors of the liver and lungs in an area with a PVC industry.

PubMed

Saric, M; Kulcar, Z; Zorica, M; Gelić, I

1976-10-01

The incidence of malignant tumors of the lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-yr period in a city with several factories, including a PVC industry. Prior to the study two cases of angio-sarcoma of the liver were diagnosed in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the period of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the same as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angiosarcoma is associated with exposure to vinyl chloride.

Malignant tumors of the liver and lungs in an area with a PVC industry.

PubMed Central

Saric, M; Kulcar, Z; Zorica, M; Gelić, I

1976-01-01

The incidence of malignant tumors of the lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-yr period in a city with several factories, including a PVC industry. Prior to the study two cases of angio-sarcoma of the liver were diagnosed in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the period of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the same as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angiosarcoma is associated with exposure to vinyl chloride. PMID:1026404

Metastasis to the appendix from adenocarcinoma of the ascending colon

PubMed Central

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-01-01

Abstract Rationale: Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. Patient concerns and diagnoses: A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. Interventions and outcomes: This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. Lessons: An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis. PMID:28296772

Anaerobic bacteria colonizing the lower airways in lung cancer patients.

PubMed

Rybojad, Pawel; Los, Renata; Sawicki, Marek; Tabarkiewicz, Jacek; Malm, Anna

2011-01-01

Anaerobes comprise most of the endogenous oropharyngeal microflora, and can cause infections of airways in lung cancer patients who are at high risk for respiratory tract infections. The aim of this study was to determine the frequency and species diversity of anaerobes in specimens from the lower airways of lung cancer patients. Sensitivity of the isolates to conventional antimicrobial agents used in anaerobe therapy was assessed. Respiratory secretions obtained by bronchoscopy from 30 lung cancer patients were cultured onto Wilkins-Chalgren agar in anaerobic conditions at 37°C for 72-96 hours. The isolates were identified using microtest Api 20A. The minimal inhibitory concentrations for penicillin G, amoxicillin/clavulanate, piperacillin/tazobactam, cefoxitin, imipenem, clindamycin, and metronidazole were determined by E-test. A total of 47 isolates of anaerobic bacteria were detected in 22 (73.3%) specimens. More than one species of anaerobe was found in 16 (53.3%) samples. The most frequently isolated were Actinomyces spp. and Peptostreptococcus spp., followed by Eubacterium lentum, Veillonella parvula, Prevotella spp., Bacteroides spp., Lactobacillus jensenii. Among antibiotics used in the study amoxicillin/clavulanate and imipenem were the most active in vitro (0% and 2% resistant strains, respectively). The highest resistance rate was found for penicillin G and metronidazole (36% and 38% resistant strains, respectively). The results obtained confirm the need to conduct analyses of anaerobic microflora colonizing the lower respiratory tract in patients with lung cancer to monitor potential etiologic factors of airways infections, as well as to propose efficient, empirical therapy.

Prenatal diagnosis of fetal respiratory function: evaluation of fetal lung maturity using lung-to-liver signal intensity ratio at magnetic resonance imaging.

PubMed

Oka, Yasuko; Rahman, Mosfequr; Sasakura, Chihaya; Waseda, Tomoo; Watanabe, Yukio; Fujii, Ryota; Makinoda, Satoru

2014-12-01

The purpose of this retrospective study is to determine the fetal lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images for the prediction of neonatal respiratory outcome. One hundred ten fetuses who underwent magnetic resonance imaging (MRI) examination for various indications after 22 weeks of gestation participated in this study. LLSIR was measured as the ratio of signal intensities of the fetal lung and liver on T2-weighted images at MRI. We examined the changes of the ratio with advancing gestation and the relations between LLSIR and the presence of the severe respiratory disorder (SRD) after birth. The best cut-off value of the LLSIR to predict respiratory outcome after birth was calculated using receiver operating characteristic (ROC) curve analysis. Lung-to-liver signal intensity ratio correlated significantly with advancing gestational age (R = 0.35, p < 0.001). The non-SRD group had higher LLSIR compared with the SRD group (2.15 ± 0.30 vs. 1.53 ± 0.40, p < 0.001). ROC curve analysis showed that fetuses with an LLSIR < 2.00 were more likely to develop SRD [sensitivity: 100%, 95% confidence interval (CI): 52-100%; specificity: 73%, 95% CI 54-88%]. The fetal LLSIR on T2-weighted images is an accurate marker to diagnose the fetal lung maturity. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garty, I.; Tal, I.; Kaynan, A.

1984-06-01

Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

Allometric scaling of fatty acyl chains in fowl liver, lung and kidney, but not in brain phospholipids.

PubMed

Szabó, András; Mézes, Miklós; Romvári, Róbert; Fébel, Hedvig

2010-03-01

The phospholipid (PL) fatty acyl chain (FA) composition (mol%) was determined in the kidney, liver, lung and brain of 8 avian species ranging in body mass from 150g (Japanese quail, Coturnix coturnix japonica) to 19kg (turkey, Meleagris gallopavo). In all organs except the brain, docosahexaenoic acid (C22:6 n3, DHA) was found to show a negative allometric scaling (allometric exponent: B=-0.18; -0.20 and -0.24, for kidney, liver and lung, respectively). With minor inter-organ differences, smaller birds had more n3 FAs and longer FA chains in the renal, hepatic and pulmonary PLs. Comparing our results with literature data on avian skeletal muscle, liver mitochondria and kidney microsomes and divergent mammalian tissues, the present findings in the kidney, liver and lung PLs seem to be a part of a general relationship termed "membranes as metabolic pacemakers". Marked negative allometric scaling was found furthermore for the tissue malondialdehyde concentrations in all organs except the brain (B=-0.17; -0.13 and -0.05, respectively). In the liver and kidney a strong correlation was found between the tissue MDA and DHA levels, expressing the role of DHA in shaping the allometric properties of membrane lipids. 2009 Elsevier Inc. All rights reserved.

Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon.

PubMed

Lukasiak, S; Schiller, C; Oehlschlaeger, P; Schmidtke, G; Krause, P; Legler, D F; Autschbach, F; Schirmacher, P; Breuhahn, K; Groettrup, M

2008-10-09

The mRNA of the ubiquitin-like modifier FAT10 has been reported to be overexpressed in 90% of hepatocellular carcinoma (HCC) and in over 80% of colon, ovary and uterus carcinomas. Elevated FAT10 expression in malignancies was attributed to transcriptional upregulation upon the loss of p53. Moreover, FAT10 induced chromosome instability in long-term in vitro culture, which led to the hypothesis that FAT10 might be involved in carcinogenesis. In this study we show that interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha synergistically upregulated FAT10 expression in liver and colon cancer cells 10- to 100-fold. Real-time RT-PCR revealed that FAT10 mRNA was significantly overexpressed in 37 of 51 (72%) of human HCC samples and in 8 of 15 (53%) of human colon carcinomas. The FAT10 cDNA sequences in HCC samples were not mutated and intact FAT10 protein was detectable. FAT10 expression in both cancer tissues correlated with expression of the IFN-gamma- and TNF-alpha-dependent proteasome subunit LMP2 strongly suggesting that proinflammatory cytokines caused the joint overexpression of FAT10 and LMP2. NIH3T3 transformation assays revealed that FAT10 had no transforming capability. Taken together, FAT10 qualifies as a marker for an interferon response in HCC and colon carcinoma but is not significantly overexpressed in cancers lacking a proinflammatory environment.

Lung cancer

MedlinePlus

Cancer - lung ... lung cancer than of breast, colon, and prostate cancers combined. Lung cancer is more common in older adults. It ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung: non-small cell lung cancer and small cell ...

Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa.

PubMed

Zeng, Huawei; Yan, Lin; Cheng, Wen-Hsing; Uthus, Eric O

2011-08-01

The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.

Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006.

PubMed

Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Webster, Angela C; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

2015-11-01

Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression-related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Study of ASN007 in Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-29

Cancer; Malignancy; Neoplasia; Neoplasm; Neoplasm Metastasis; Colon Cancer; Colonic Neoplasms; Colon Cancer Liver Metastasis; Metastatic Cancer; Metastatic Melanoma; Metastatic Colon Cancer; Metastatic Lung Cancer; Non Small Cell Lung Cancer Metastatic; Pancreatic Cancer; Pancreas Cancer; Pancreas Adenocarcinoma; Pancreas Neoplasm; Metastatic Nonsmall Cell Lung Cancer; Metastatic Pancreatic Cancer

Gallium scintigraphic pattern in lung CMV infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganz, W.I.; Cohen, D.; Mallin, W.

1994-05-01

Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes.

PubMed

Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R Elaine; Vincent, Isaah S; Burdick, Marie D; Kadl, Alexandra; Mehrad, Borna

2016-06-15

Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. M-CSF has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia, and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and antimicrobial functions of mononuclear phagocytes in the lungs and liver. Copyright © 2016 by The American Association of Immunologists, Inc.

M-CSF mediates host defense during bacterial pneumonia by promoting the survival of lung and liver mononuclear phagocytes

PubMed Central

Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R. Elaine; Vincent, Isaah S.; Burdick, Marie D.; Kadl, Alexandra; Mehrad, Borna

2016-01-01

Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. Macrophage-colony stimulating factor (M-CSF) has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, the proliferation of precursors or the recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and anti-microbial functions of both lung and liver mononuclear phagocytes during pneumonia and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and anti-microbial functions of mononuclear phagocytes in the lungs and liver. PMID:27183631

Efficient zinc uptake is critical for the ability of Pseudomonas aeruginosa to express virulence traits and colonize the human lung.

PubMed

Mastropasqua, Maria Chiara; Lamont, Iain; Martin, Lois W; Reid, David W; D'Orazio, Melania; Battistoni, Andrea

2018-07-01

We have recently shown that Pseudomonas aeruginosa, an opportunistic pathogen that chronically infects the lungs of patients with cystic fibrosis (CF) and other forms of lung disease, is extremely efficient in recruiting zinc from the environment and that this capability is required for its ability to cause acute lung infections in mice. To verify that P. aeruginosa faces zinc shortage when colonizing the lungs of human patients, we analyzed the expression of three genes that are highly induced under conditions of zinc deficiency (zrmA, dksA2 and rpmE2), in bacteria in the sputum of patients with inflammatory lung disease. All three genes were expressed in all the analyzed sputum samples to a level much higher than that of bacteria grown in zinc-containing laboratory medium, supporting the hypothesis that P. aeruginosa is under zinc starvation during lung infections. We also found that the expression of several virulence traits that play a central role in the ability of P. aeruginosa to colonize the lung is affected by disruption of the most important zinc importing systems. Virulence features dependent on zinc intake include swarming and swimming motility and the ability to form biofilms. Furthermore, alterations in zinc assimilation interfere with the synthesis of the siderophore pyoverdine, suggesting that zinc recruitment could modulate iron uptake and affect siderophore-mediated cell signaling. Our results reveal that zinc uptake is likely to play a key role in the ability of P. aeruginosa to cause chronic lung infections and strongly modulates critical virulence traits of the pathogen. Taking into account the recent discovery that zinc uptake in P. aeruginosa is promoted by the release of a small molecular weight molecule showing high affinity for zinc, our data suggest novel and effective possibilities to control lung infections by these bacteria. Copyright © 2018 Elsevier GmbH. All rights reserved.

Viral colonization in exhaled breath condensate of lung cancer patients: Possible role of EBV and CMV.

PubMed

Carpagnano, Giovanna E; Lacedonia, Donato; Natalicchio, Maria Iole; Cotugno, Grazia; Zoppo, Luigi; Martinelli, Domenico; Antonetti, Raffaele; Foschino-Barbaro, Maria Pia

2018-02-01

Today, an increasing interest is being addressed to the viral etiology of lung tumors. As a consequence, research efforts are currently being directed to the identification of the new viruses involved in lung carcinogenesis toward which the screening programs could be directed. The aim of this study was to investigate the airways colonization by the Epstein-Barr virus (EBV) and Citomegalovirus (CMV) in patients affected by lung cancer using, as a respiratory non-invasive sample, the exhaled breath condensate (EBC). About 70 lung-cancer patients and 40 controls were enrolled. All subjects underwent bronchial brushing and EBC collection. EBV-DNA and CMV-DNA were evaluated in both samples by real-time PCR assay. They were able to detect EBV and CMV in the EBC. An increase of the EBV positivity in non-small cell lung cancer (NSCLC) patients compared with controls and of the CMV in advanced stages of lung cancer were observed. The association of the positivity of the cytology and the CMV test (in EBC or brushing) slightly increased the sensitivity of malignant diagnosis. EBV and CMV resulted detectable in the EBC. In consideration of the potential involvement of these viruses in lung cancer, which was confirmed in this study, future studies in this direction were supported. © 2016 John Wiley & Sons Ltd.

Oxygen toxicity in the perfused rat liver and lung under hyperbaric conditions.

PubMed Central

Nishiki, K; Jamieson, D; Oshino, N; Chance, B

1976-01-01

1. In the lung and liver of tocopherol-deficient rats, the activities of glutathione peroxidase and glucose 6-phosphate dehydrogenase were increased substantially, suggesting an important role for both enzymes in protecting the organ against the deleterious effects of lipid peroxides. 2. Facilitation of the glutathione peroxidase reaction by infusing t-butyl hydroperoxide caused the oxidation of nicotinamide nucleotides and glutathione, resulting in a concomitant increase in the rate of release of oxidized glutathione into the perfusate. Thus the rate of production of lipid peroxide and H2O2 in the perfused organ could be compared by simultaneous measurement of the rate of glutathione release and the turnover number of the catalase reaction. 3. On hyperbaric oxygenation at 4 X 10(5)Pa, H2O2 production, estimated from the turnover of the catalase reaction, was increased slightly in the liver, and glutathione release was increased slightly, in both lung and liver. 4. Tocopherol deficiency caused a marked increase in lipid-peroxide formation as indicated by a corresponding increase in glutathione release under hyperbaric oxygenation, with a further enhancement when the tocopherol-deficient rats were also starved. 5. The study demonstrates that the primary response to hyperbaric oxygenation is an elevation of the rate of lipid peroxidation rather than of the rate of formation of H2O2 or superoxide. PMID:12754

Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Cheol-Hun; Department of Biochemistry, Pusan National University School of Medicine, Yangsan; Bae, Jae-Ho

2015-06-01

Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control andmore » irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.« less

Inhibition of liver metastases from neuraminidase-treated colon 26 cells by an anti-Thomsen-Friedenreich-specific monoclonal antibody.

PubMed

Shigeoka, H; Karsten, U; Okuno, K; Yasutomi, M

1999-01-01

Thomsen-Friedenreich antigen (TF; Galbeta1-3GalNAcalpha1-) is expressed on many human carcinomas. Evidence suggests that TF-carrying tumor cells specifically bind asialoglycoprotein receptors on hepatocytes resulting in metastasis formation in the liver. We used an animal model to examine the feasibility of preventing metastasis formation by an antibody to TF. Treatment of Colon 26 cells with neuraminidase led to the exposure of TF, and consequently to a higher frequency of liver metastases in syngeneic Balb/c mice. This could be prevented by an antibody to TF (A78-G/A7), but not by a control antibody. The results may open up a new strategy for the prophylaxis of metastatic spread to the liver.

Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-12-16

Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Metastasis to the appendix from adenocarcinoma of the ascending colon: A case report.

PubMed

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-03-01

Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis.

Accumulation of heavy metals and As in liver, hair, femur, and lung of Persian jird (Meriones persicus) in Darreh Zereshk copper mine, Iran.

PubMed

Khazaee, Manoochehr; Hamidian, Amir Hossein; Alizadeh Shabani, Afshin; Ashrafi, Sohrab; Mirjalili, Seyyed Ali Ashghar; Esmaeilzadeh, Esmat

2016-02-01

Rodents frequently serve as bioindicator to monitor the quality of the environment. Concentrations of 11 elements (Cd, Co, Ti, Fe, Mn, Cu, Sb, As, Sr, Ni, and Cr) were investigated and compared in liver, hair, femur, and lung of the Persian jird (Meriones persicus) from Darreh Zereshk copper mine, Iran. Metals were determined in different tissues of 39 individuals of Persian jird, collected by snap trap in 2014 from five areas of Darreh Zereshk copper mine. Samples were prepared by wet digestion method, and the contents of elements were analyzed with ICP-OES (VARIAN, 725-ES) instrument. Cadmium, Sb, and Co were below the limit of detection, and Mn and As were found only in hair and liver tissues. We detected the highest concentration of Cu, As, Ti, Fe, Mn, Cr, and Ni in hair in comparison with other tissues. Significant higher levels of Ti in femur and hair; Fe in liver and hair; Mn in liver; As in hair; Sr in lung; Cr in lung, hair, femur, and liver; Cu in femur; and Ni in liver and lung tissues were observed in females. Nearly all element concentrations in the tissues of Persian jird from flotation site, Darreh Zereshk and Hasan Abad villages and leaching site (mining areas) were higher than those from tailing dump site (reference site). We found the highest concentrations of As in liver and hair; Ni and Cr in liver, hair, and lung; and Sr in lung and hair tissues of Persian jird in leaching site. We tried to specify the status of elements before fully exploitation of Darreh Zereshk copper mine by using bioindicator species. Based on our achievements, initial activities did not strongly pollute the surrounded environment of the mine. The high abundance of Persian jird as well as their several proper features makes them a suitable species for biomonitoring programs especially for further studies will be performed after full exploitation of Darreh Zereshk copper mine.

Optimization of the Agar-gel Method for Isolation of Migrating Ascaris suum Larvae From the Liver and Lungs of Pigs

PubMed Central

Saeed, I; Roepstorff, A; Rasmussen, T; Høg, M; Jungersen, G

2001-01-01

Experiments on use of an agar-gel method for recovery of migrating Ascaris suum larvae from the liver and lungs of pigs were conducted to obtain fast standardized methods. Subsamples of blended tissues of pig liver and lungs were mixed with agar to a final concentration of 1% agar and the larvae allowed to migrate out of the agar-gel into 0.9% NaCl at 38°C. The results showed that within 3 h more than 88% of the recoverable larvae migrated out of the liver agar-gel and more than 83% of the obtained larvae migrated out of the lung agar-gel. The larvae were subsequently available in a very clean suspension which reduced the sample counting time. Blending the liver for 60 sec in a commercial blender showed significantly higher larvae recovery than blending for 30 sec. Addition of gentamycin to reduce bacterial growth during incubation, glucose to increase larval motility during migration or ice to increase sedimentation of migrated larvae did not influence larvae recovery significantly. PMID:11503373

Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasi, Maria Lauda; USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033; The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033

Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70–75%, increased apoptosismore » and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. -- Highlights: • MAT2A knockdown depletes putrescine and leads to apoptosis. • Putrescine attenuates MAT2A knockdown-induced apoptosis and

Native and β-cyclodextrin-enclosed curcumin: entrapment within liposomes and their in vitro cytotoxicity in lung and colon cancer.

PubMed

Rahman, Shafiur; Cao, Siyu; Steadman, Kathryn J; Wei, Ming; Parekh, Harendra S

2012-01-01

With a view to improving the solubility and delivery characteristics of poorly water-soluble drugs, we prepared β-cyclodextrin-curcumin (βCD-C) inclusion complexes (hydrophilic curcumin) and entrapped both native curcumin (hydrophobic) and the complexes separately into liposomes; these were then assessed for in vitro cytotoxicity in lung and colon cancer cell lines. Optimization of curcumin entrapment within βCD was achieved, with the resultant βCD-C complexes prepared by methanol reflux. Inclusion complexes were confirmed using UV spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction. The water solubility of βCD-C complexes improved markedly (c.f. native curcumin) and successful entrapment of complexes into liposomes, prepared using a thin-film hydration approach, was also achieved. All the liposomal formulations were characterized for curcumin and βCD-C complex entrapment efficiency, particle size, polydispersity and stability at 2-8°C. Curcumin, βCD-C complex and their optimized liposomal formulations were evaluated for anticancer activity in lung (A-459) and colon (SW-620) cancer cell lines. All curcumin-containing formulations tested were effective in inhibiting cell proliferation, as determined via an MTT assay. The median effective dose (EC(50)) for all curcumin formulations was found to be in the low µM range for both lung and colon cancer cell lines tested. Our results confirm that βCD inclusion complexes of poorly water soluble drugs, such as curcumin can be entrapped within biocompatible vesicles such as liposomes, and this does not preclude their anticancer activity.

Colorectal breast carcinoma metastasis diagnosed as an obstructive colonic primary tumor. A case report and review of the literature.

PubMed

Théraux, J; Bretagnol, F; Guedj, N; Cazals-Hatem, D; Panis, Y

2009-12-01

Common sites of colorectal breast carcinoma metastasis are bones, lungs, the central nervous system and the liver. Metastases in the gastrointestinal (GI) tract are rare and especially involve the stomach rather than the colon. Clinical or radiological features usually cannot differentiate them from a primary colorectal tumor, resulting in inappropriate treatment. In some cases, this lesion suggests multifocal spread of breast cancer with peritoneal carcinomatosis. Colorectal breast cancer metastasis is a rare finding and there is no consensus on the management of these lesions. The present case report describes a 69-year-old female with metastatic breast cancer presenting as an obstructive tumor of the transverse colon.

Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spink, Barbara C.; Bloom, Michael S.; Wu, Susan

The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5more » species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2

Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche

PubMed Central

Aguado, Brian A.; Caffe, Jordan R.; Nanavati, Dhaval; Rao, Shreyas S.; Bushnell, Grace G.; Azarin, Samira M.; Shea, Lonnie D.

2016-01-01

Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. PMID:26844426

Down-regulation of liver-intestine cadherin enhances noscapine-induced apoptosis in human colon cancer cells.

PubMed

Tian, Xia; Liu, Meng; Zhu, Qingxi; Tan, Jie; Liu, Weijie; Wang, Yanfen; Chen, Wei; Zou, Yanli; Cai, Yishan; Han, Zheng; Huang, Xiaodong

2017-09-01

The aim of the present study was to explore the signaling pathway of noscapine which induces apoptosis by blocking liver-intestine cadherin (CDH17) gene in colon cancer SW480 cells. Human colon cancer SW480 cells were transfected with CDH17 interference vector and treatment with 10 µmol/L noscapine. The proliferation and apoptosis of SW480 cells were detected by MTT assay and AnnexinV-FITC/PI flow cytometry kit (BD), respectively. Cell invasion were assessed by transwell assays. Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot. Compared to the noscapine group, the proliferation was decreased significantly and the apoptosis was increased significantly in SW480 cells of the siCDH17+noscapine group. Cyt-c and Bax protein levels in siCDH17+noscapine group was higher than that of the noscapine group, but Bcl-2 and Bcl-xL protein levels in siCDH17+noscapine group were lower than that of the noscapine group. Moreover, up-expression of CDH17 inhibited the efficacy of noscapine-induced apoptosis in SW480 cells. We inferred that down-expression of extrinsic CDH17 gene can conspicuously promote apoptosis-inducing effects of noscapine on human colon cancer SW480 cells, which is a novel strategy to improve chemotherapeutic effects on colon cancer.

[Breast cancer metastases to the stomach and colon: two case reports].

PubMed

Pulanić, Roland; Jelavić, Marko; Premuzić, Marina; Opacić, Milorad; Jakic-Razumović, Jasminka; Padovan-Stern, Ranka; Vrbanec, Damir

2012-01-01

Summary. Breast cancer has a high potential for metastasis, usually to the lungs, bones, liver and lymph nodes. Metastases in the holow organs of the digestive system are rare and mainly affectes the stomach and colon. They are characterized by very different clinical and radiological manifestations. We have warned that the initial unrecognized breast cancer can appear as a primary tumor of the stomach and colon, and onlya histopathological analysis reveales that it is a metastatic breast cancer. Metastases to the stomach or intestine involve deep layer of the mucosa and pathohistological findings of standard biopsy sample can be falsely negative, despite positive imaging technique (abdominal ultrasound and MSCT, endoscopic ultrasound) that indicate the tumor process. That's,why we emphasize the importance of endoscopic mucosal resection in the detection of malignant process of deeper layers of the gastric mucosa and deep intestinal mucosal biopsies with postoperative analysis of its walls.

Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung Colonization in Adult Cystic Fibrosis Patients.

PubMed

Seidler, Darius; Griffin, Mary; Nymon, Amanda; Koeppen, Katja; Ashare, Alix

2016-01-01

Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF. Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum sample was obtained from subjects who were able to spontaneously expectorate. All samples were sent for standard microbiology culture. Using BAL as the gold standard, we found the positive predictive value for Pseudomonas aeruginosa to be 100% in both sputum and throat swab compared to BAL. However, the negative predictive value for P. aeruginosa was 60% and 50% in sputum and throat swab, respectively. Conversely, the positive predictive value for Staphylococcus aureus was 57% in sputum and only 41% in throat swab and the negative predictive value of S. aureus was 100% in sputum and throat swab compared to BAL. Our data show that positive sputum and throat culture findings of P. aeruginosa reflect results found on BAL fluid analysis, suggesting these are reasonable surrogates to determine lung colonization with P. aeruginosa. However, sputum and throat culture findings of S. aureus do not appear to reflect S. aureus colonization of the lung.

Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

PubMed

Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

2014-01-01

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

PubMed Central

Kaur, Ravinder; Surendran, Naveen; Ochs, Martina

2014-01-01

Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection. PMID:25245804

Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

PubMed

Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

2017-09-15

Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of urban environment on oxidative damage (TBARS) and antioxidant systems in lungs and liver of great tits, Parus major.

PubMed

Isaksson, C; Sturve, J; Almroth, B C; Andersson, S

2009-01-01

A direct negative link between human health and urban pollution levels generated by increased internal levels of oxyradicals is well established. The impact of urban environment on the physiology of wild birds is however, poorly investigated. Here we compare oxidative damage (i.e., lipid peroxidation, measured as TBARS) and different antioxidant enzymes (glutathione reductase (GR), glutathione-S-transferase (GST), and catalase (CAT)) in lungs of urban and rural great tits, Parus major. In addition, we investigated enzymatic (i.e., CAT) and non-enzymatic (i.e., carotenoids) antioxidant levels in liver tissue. There was no significant difference in lipid peroxidation in lungs between the environments. Among the antioxidant enzymes measured in lungs, only CAT showed a tendency towards increased activity in the urban environment. In contrast, CAT in livers was highly non-significant. However, there was a significantly higher concentration of dietary carotenoids (i.e., lutein (Lut) and zeaxanthin (Zx)) in urban males, along with a sex-specific difference in composition (Lut:Zx ratio) between the environments. Taken together, these results suggest that great tit lungs and livers do not seem to be negatively affected, regarding oxidative stress, by living in an urban environment.

Comparing a medical records-based and a claims-based index for measuring comorbidity in patients with lung or colon cancer.

PubMed

Kehl, Kenneth L; Lamont, Elizabeth B; McNeil, Barbara J; Bozeman, Samuel R; Kelley, Michael J; Keating, Nancy L

2015-05-01

Ascertaining comorbid conditions in cancer patients is important for research and clinical quality measurement, and is particularly important for understanding care and outcomes for older patients and those with multi-morbidity. We compared the medical records-based ACE-27 index and the claims-based Charlson index in predicting receipt of therapy and survival for lung and colon cancer patients. We calculated the Charlson index using administrative data and the ACE-27 score using medical records for Veterans Affairs patients diagnosed with stage I/II non-small cell lung or stage III colon cancer from January 2003 to December 2004. We compared the proportion of patients identified by each index as having any comorbidity. We used multivariable logistic regression to ascertain the predictive power of each index regarding delivery of guideline-recommended therapies and two-year survival, comparing the c-statistic and the Akaike information criterion (AIC). Overall, 97.2% of lung and 90.9% of colon cancer patients had any comorbidity according to the ACE-27 index, versus 59.5% and 49.7%, respectively, according to the Charlson. Multivariable models including the ACE-27 index outperformed Charlson-based models when assessing receipt of guideline-recommended therapies, with higher c-statistics and lower AICs. Neither index was clearly superior in prediction of two-year survival. The ACE-27 index measured using medical records captured more comorbidity and outperformed the Charlson index measured using administrative data for predicting receipt of guideline-recommended therapies, demonstrating the potential value of more detailed comorbidity data. However, the two indices had relatively similar performance when predicting survival. Copyright © 2015 Elsevier Inc. All rights reserved.

The Protective Effect of Selenium on Oxidative Stress Induced by Waterpipe (Narghile) Smoke in Lungs and Liver of Mice.

PubMed

Charab, Mohamad A; Abouzeinab, Noura S; Moustafa, Mohamed E

2016-12-01

Waterpipe smoking is common in the Middle East populations and results in health problems. In this study, we investigated the effects of exposure of mice to waterpipe smoke on oxidative stress in lungs and liver and the effects of selenium administration before smoke exposure on the oxidative stress. Twenty-four mice were divided equally into four groups: (i) the control mice received no exposure or treatment; (ii) mice exposed to waterpipe smoke; (iii) mice received intraperitoneal injection of 0.59 μg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke; and (iv) mice received intraperitoneal injection of 1.78 μg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke. Mice were exposed to waterpipe smoke every other day for four times within 8 successive days. Malondialdehyde and nitric oxide levels were significantly higher in the lungs and liver, while the activities of superoxide dismutase, glutathione peroxidase-1, and catalase were significantly lower in the waterpipe smoke group when compared to control mice. Treating mice with 1.78 μg selenium/kg body weight significantly restored the normal levels of these parameters. Histological examinations of lungs and liver confirmed the protective actions of selenium against the effects of exposure to waterpipe smoke. In conclusion, exposure of mice to waterpipe smoke-induced oxidative stress in lungs and liver. Administration of low level of selenium, 1.78 μg selenium/kg body weight as sodium selenite, exerted protective effects against oxidative stress induced by exposure to waterpipe smoke.

Human antibodies to PhtD, PcpA, and Ply reduce adherence to human lung epithelial cells and murine nasopharyngeal colonization by Streptococcus pneumoniae.

PubMed

Kaur, Ravinder; Surendran, Naveen; Ochs, Martina; Pichichero, Michael E

2014-12-01

Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma.

PubMed

Bayazit, Vahdettin

2004-02-01

To study, the cytotoxic effects of some biological and chemical agents on G1, S, G2, M and G0 phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (DMBA) and cadmium chloride. Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of DMBA in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were grown at 37 degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization. Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01). This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells. This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans.

Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

ClinicalTrials.gov

2017-04-05

Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab: A case report.

PubMed

Nozawa, Yoshihiro; Oka, Yuka; Oosugi, Jun; Takemura, Shinichi

2018-05-01

Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. Biopsy examination revealed squamous cell carcinoma in the right lung and adenocarcinoma of the sigmoid colon. The patient underwent successful pembrolizumab treatment as first-line immunotherapy for lung cancer, as demonstrated by computed tomography, and the sigmoid colon tumor was excised during an immunotherapy-free window. No unusual tumor growth in the right lung or abnormal abdominal signs was observed during the 9-month follow-up. Microscopically, the resected colon cancer specimen was characterized by numerous lymphoid cells in the partial stroma, with a large number of infiltrating lymphocytes consisting of CD3+, CD8+ T cells. In summary, this case demonstrates how immunotherapy affects PD-L1-negative colon cancer and indicates future treatment prospects.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

PubMed

Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem

2006-08-31

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

Thrombin stimulates increased plasminogen activator inhibitor-1 release from liver compared to lung endothelium.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Gonzalez, Eduardo; Kelher, Marguerite R; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C

2018-05-01

Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of the fibrinolytic system, covalently binding to tissue plasminogen activator and blocking its activity. Fibrinolysis shutdown is evident in the majority of severely injured patients in the first 24 h and is thought to be due to PAI-1. The source of this PAI-1 is thought to be predominantly endothelial cells, but there are known organ-specific differences, with higher levels thought to be in the liver. Thrombin generation is also elevated in injured patients and is a potent stimulus for PAI-1 release in human umbilical endothelial cells. We hypothesize that thrombin induces liver endothelial cells to release increased amounts of PAI-1, versus pulmonary endothelium, consisting of both stored PAI-1 and a larger contribution from de novo PAI-1 synthesis. Human liver sinusoidal endothelial cells (LSECs) and human microvascular lung endothelial cells (HMVECs) were stimulated in vitro ± thrombin (1 and 5 IU/mL) for 15-240 min, the supernatants were collected, and PAI-1 was measured by enzyme-linked immunosorbent assays. To elucidate the PAI-1 contribution from storage versus de novo synthesis, cycloheximide (10 μg/mL) was added before thrombin in separate experiments. While both LSECs and HMVECs rapidly stimulated PAI-1 release, LSECs released more PAI-1 than HMVECs in response to high-dose thrombin, whereas low-dose thrombin did not provoke immediate release. LSECs continued to release PAI-1 over the ensuing 240 min, whereas HMVECs did not. Cycloheximide did not inhibit early PAI-1 release from LSECs but did at the later time points (30-240 min). Thrombin elicits increased amounts of PAI-1 release from liver endothelium compared with lung, with a small presynthesized stored contribution and a later, larger increase in PAI-1 release via de novo synthesis. This study suggests that the liver may be an important therapeutic target for inhibition of the hypercoagulable surgical patient and the

Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice

USDA-ARS?s Scientific Manuscript database

We investigated the anti-metastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of Hericium erinaceus strongly elicited ca...

Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease.

PubMed

Jaat, Fathia G; Hasan, Sajidah F; Perry, Audrey; Cookson, Sharon; Murali, Santosh; Perry, John D; Lanyon, Clare V; De Soyza, Anthony; Todryk, Stephen M

2018-05-30

As a way to determine markers of infection or disease informing disease management, and to reveal disease-associated immune mechanisms, this study sought to measure antibody and T cell responses against key lung pathogens and to relate these to patients' microbial colonization status, exacerbation history and lung function, in Bronchiectasis (BR) and Chronic Obstructive Pulmonary Disease (COPD). One hundred nineteen patients with stable BR, 58 with COPD and 28 healthy volunteers were recruited and spirometry was performed. Bacterial lysates were used to measure specific antibody responses by ELISA and T cells by ELIspot. Cytokine secretion by lysate-stimulated T cells was measured by multiplex cytokine assay whilst activation phenotype was measured by flow cytometry. Typical colonization profiles were observed in BR and COPD, dominated by P.aeruginosa, H.influenzae, S.pneumoniae and M.catarrhalis. Colonization frequency was greater in BR, showing association with increased antibody responses against P.aeruginosa compared to COPD and HV, and with sensitivity of 73% and specificity of 95%. Interferon-gamma T cell responses against P.aeruginosa and S.pneumoniae were reduced in BR and COPD, whilst reactive T cells in BR had similar markers of homing and senescence compared to healthy volunteers. Exacerbation frequency in BR was associated with increased antibodies against P. aeruginosa, M.catarrhalis and S.maltophilia. T cell responses against H.influenzae showed positive correlation with FEV 1 % (r = 0.201, p = 0.033) and negative correlation with Bronchiectasis Severity Index (r = - 0.287, p = 0.0035). Our findings suggest a difference in antibody and T cell immunity in BR, with antibody being a marker of exposure and disease in BR for P.aeruginosa, M.catarrhalis and H.influenzae, and T cells a marker of reduced disease for H.influenzae.

Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer.

PubMed

Nielsen, Vance G; Matika, Ryan W; Ley, Michele L B; Waer, Amy L; Gharagozloo, Farid; Kim, Samuel; Nfonsam, Valentine N; Ong, Evan S; Jie, Tun; Warneke, James A; Steinbrenner, Evangelina B

2014-04-01

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was compared to normal individual plasma (n = 30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.

Apple juice intervention modulates expression of ARE-dependent genes in rat colon and liver.

PubMed

Soyalan, Bülent; Minn, Jutta; Schmitz, Hans J; Schrenk, Dieter; Will, Frank; Dietrich, Helmut; Baum, Matthias; Eisenbrand, Gerhard; Janzowski, Christine

2011-03-01

The risk of cancer and other degenerative diseases is inversely correlated with consumption of fruits and vegetables. This beneficial effect is mainly attributed to secondary plant constituents such as polyphenols, supposed to play a major role in protection against ROS (reactive oxygen species)-associated toxicity. To elucidate the potential of differently manufactured apple juices (clear AJ/cloudy AJ/smoothie, in comparison with a polyphenol-free control juice) to modulate expression of ARE-dependent genes. In male Sprague-Dawley rats (n = 8/group; 10d juice intervention, 4d wash-out; 4 treatment cycles), expression of target genes (superoxide dismutase, SOD1/SOD2; glutathione peroxidase, GPX1/GPX2; γ-glutamylcysteine ligase, GCLC/GCLM; glutathione reductase, GSR; catalase, CAT; NAD(P)H:quinone oxidoreductase-1, NQO1 and transcription factor erythroid-derived 2-like-2, Nrf2) was quantified with duplex RT-PCR, using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control. In colon and liver of rats consuming polyphenol-free control juice, rather similar basic expressions were observed (relative GAPDH ratios ranging from 2 to 0.7 and 2.5-0.3, respectively). In the distal colon, apple juice intervention slightly but significantly induced most genes (e.g. GPX2, GSR, CAT, Nrf2; p < 0.001), whereas in the liver only GPX1 and NQO1 mRNA were up-regulated; other hepatic target genes were not affected or down-regulated (SOD1, SOD2, GCLC/M, GSR), concomitant with the absence of Nrf2 induction. Induction of antioxidant gene expression differed with juice type (cloudy AJ > clear AJ ~ smoothie). Taken together, the results underline the potential of polyphenol-rich apple juice to increase the expression of ARE-dependent antioxidant genes.

Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.

PubMed

Uchiyama, Munehito; Tojo, Kentaro; Yazawa, Takuya; Ota, Shuhei; Goto, Takahisa; Kurahashi, Kiyoyasu

2015-04-01

Lung injury is a major clinical concern after hepatic ischemia-reperfusion (I/R), due to the production of reactive oxygen species in the reperfused liver. We investigated the efficacy of edaravone, a potent free-radical scavenger, for attenuating lung injury after hepatic I/R. Adult male Sprague-Dawley rats were assigned to sham + normal saline (NS), I/R + NS, or I/R + edaravone group. Rats in the I/R groups were subjected to 90 min of partial hepatic I/R. Five minutes before reperfusion, 3 mg/kg edaravone was administered to the I/R + edaravone group. After 6 h of reperfusion, we evaluated lung histopathology and wet-to-dry ratio. We also measured malondialdehyde (MDA), an indicator of oxidative stress, in the liver and the lung, as well as cytokine messenger RNA expressions in the reperfused liver and plasma cytokine concentrations. Histopathology revealed lung damages after 6 h reperfusion of partial ischemic liver. Moreover, a significant increase in lung wet-to-dry ratio was observed. MDA concentration increased in the reperfused liver, but not in the lungs. Edaravone administration attenuated the lung injury and the increase of MDA in the reperfused liver. Edaravone also suppressed the reperfusion-induced increase of interleukin-6 messenger RNA expressions in the liver and plasma interleukin-6 concentrations. Edaravone administration before reperfusion of the ischemic liver attenuates oxidative stress in the reperfused liver and the subsequent lung injury. Edaravone may be beneficial for preventing lung injury induced by hepatic I/R. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

ClinicalTrials.gov

2014-05-28

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

Simultaneous Subcutaneous and Lung Hydatid Disease.

PubMed

Karaarslan, Kerem; Koçal, Sedat; Durgun Yetim, Tülin

2017-03-01

Hydatid disease is still endemic in Turkey. The most common site is the liver, followed by the lungs; it is rarely observed in the other parts of the body. In this case, right lung and subclavicular subcutaneous hydatid cysts were simultaneously observed. Cystotomy and capitonnage via minithoracotomy were applied for the cyst in the lung, and the subclavicular subcutaneous hydatid cyst was completely excised. Histopathological diagnosis was confirmed. Cystic lesions localized in the body except the liver and lung hydatid disease should always assessing kept in mind. It should not be forgotten that the cyst in the lung and liver may be detected simultaneously in other parts of the body.

Hematogenous umbilical metastasis from colon cancer treated by palliative single-incision laparoscopic surgery

PubMed Central

Hori, Tomohide; Okada, Noriyuki; Nakauchi, Masaya; Hiramoto, Shuji; Kikuchi-Mizota, Ayako; Kyogoku, Masahisa; Oike, Fumitaka; Sugimoto, Hidemitsu; Tanaka, Junya; Morikami, Yoshiki; Shigemoto, Kaori; Ota, Toyotsugu; Kaneko, Masanobu; Nakatsuji, Masato; Okae, Shunji; Tanaka, Takahiro; Gunji, Daigo; Yoshioka, Akira

2013-01-01

Sister Mary Joseph’s nodule (SMJN) is a rare umbilical nodule that develops secondary to metastatic cancer. Primary malignancies are located in the abdomen or pelvis. Patients with SMJN have a poor prognosis. An 83-year-old woman presented to our hospital with a 1-month history of a rapidly enlarging umbilical mass. Endoscopic findings revealed advanced transverse colon cancer. computer tomography and fluorodeoxyglucose-positron emission tomography revealed tumors of the transverse colon, umbilicus, right inguinal lymph nodes, and left lung. The feeding arteries and drainage veins for the SMJN were the inferior epigastric vessels. Imaging findings of the left lung tumor allowed for identification of the primary lung cancer, and a diagnosis of advanced transverse colon cancer with SMJN and primary lung cancer was made. The patient underwent local resection of the SMNJ and subsequent single-site laparoscopic surgery involving right hemicolectomy and paracolic lymph node dissection. Intra-abdominal dissemination to the mesocolon was confirmed during surgery. Histopathologically, the transverse colon cancer was confirmed to be moderately differentiated tubular adenocarcinoma. We suspect that SMJN may occur via a hematogenous pathway. Although chemotherapy for colon cancer and thoracoscopic surgery for the primary lung cancer were scheduled, the patient and her family desired home hospice. Seven months after surgery, she died of rapidly growing lung cancer. PMID:24179626

Comparison of traditional microbiological culture and 16S polymerase chain reaction analyses for identification of preoperative airway colonization for patients undergoing lung resection.

PubMed

Howitt, Samuel H; Blackshaw, Diana; Fontaine, Eustace; Hassan, Ibrahim; Malagon, Ignacio

2018-04-28

Preoperative airway colonization is associated with increased risk of postoperative respiratory complications following lung resection. This study compares the rates of preoperative lower respiratory tract colonization identified by traditional culture and novel 16S polymerase chain reaction (PCR) tests. Preoperative sputum and bronchoalveolar lavage (BAL) samples for 49 lung resection patients underwent culture and 16S PCR analyses. Rates of positive test results were determined and relationships between test results and suspected postoperative respiratory tract infection and hospital length of stay (LOS) were investigated. Preoperative BAL cultures were positive for 29 (59.2%) patients (population estimate 95%CI 45.2%-71.8%). 16S PCR tests were positive for 28 (57.1%) patients (population estimate 95%CI 43.3%-70.0%). 17 (34.7%) patients suffered suspected postoperative respiratory tract infection (population estimate 95%CI 22.9%-48.7%). Positive 16S PCR results tended to be associated with longer LOS (median 7.5 days vs 4.0 days for negative, p = 0.08) and increased risk of suspected postoperative respiratory tract infection (46.4% for positive vs 19.0% for negative, p = 0.07). Rates of colonization identified by culture and 16S PCR analyses of BAL samples were similar. Future research should attempt to clarify associations between airway colonization identified by 16S PCR and outcomes. 16S PCR may be useful when stratifying risk of postoperative respiratory complications. Copyright © 2018 Elsevier Inc. All rights reserved.

Postoperative weight gain during the first year after kidney, liver, heart, and lung transplant: a prospective study.

PubMed

Kugler, Christiane; Einhorn, Ina; Gottlieb, Jens; Warnecke, Gregor; Schwarz, Anke; Barg-Hock, Hannelore; Bara, Christoph; Haller, Hermann; Haverich, Axel

2015-03-01

Studies of all types of organ transplant recipients have suggested that weight gain, expressed as an increase in body mass index (BMI), after transplant is common. To describe weight gain during the first year after transplant and to determine risk factors associated with weight gain with particular attention to type of transplant. A prospective study of 502 consecutive organ transplant recipients (261 kidney, 73 liver, 29 heart, 139 lung) to identify patterns of BMI change. Measurements were made during regular outpatient clinical visits at 2, 6, and 12 months after transplant. Data were retrieved from patients' charts and correlated with maintenance corticosteroid doses. Overall, mean BMI (SD; range) was 23.9 (4.5; 13.6-44.1) at 2 months and increased to 25.4 (4.0; 13.0-42.2) by the end of the first postoperative year. BMI levels organized by World Health Organization categories showed a trend toward overweight/obesity in kidney (53.4%), liver (51.5%), heart (51.7%), and lung (33.1%) patients by 12 months after transplant. BMI changed significantly (P= .05) for all organ types and between all assessment points, except in kidney recipients. Maintenance corticosteroid doses were not a predictor of BMI at 12 months after transplant for most patients. Weight gain was common among patients undergoing kidney, liver, heart, and lung transplant; however, many showed BMI values close to normality at the end of the first year after transplant. In most cases, increased BMI levels were related to obesity before transplant and not to maintenance corticosteroid therapy.

Quantitative Features of Liver Lesions, Lung Nodules, and Renal Stones at Multi-Detector Row CT Examinations: Dependency on Radiation Dose and Reconstruction Algorithm.

PubMed

Solomon, Justin; Mileto, Achille; Nelson, Rendon C; Roy Choudhury, Kingshuk; Samei, Ehsan

2016-04-01

To determine if radiation dose and reconstruction algorithm affect the computer-based extraction and analysis of quantitative imaging features in lung nodules, liver lesions, and renal stones at multi-detector row computed tomography (CT). Retrospective analysis of data from a prospective, multicenter, HIPAA-compliant, institutional review board-approved clinical trial was performed by extracting 23 quantitative imaging features (size, shape, attenuation, edge sharpness, pixel value distribution, and texture) of lesions on multi-detector row CT images of 20 adult patients (14 men, six women; mean age, 63 years; range, 38-72 years) referred for known or suspected focal liver lesions, lung nodules, or kidney stones. Data were acquired between September 2011 and April 2012. All multi-detector row CT scans were performed at two different radiation dose levels; images were reconstructed with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) algorithms. A linear mixed-effects model was used to assess the effect of radiation dose and reconstruction algorithm on extracted features. Among the 23 imaging features assessed, radiation dose had a significant effect on five, three, and four of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Adaptive statistical iterative reconstruction had a significant effect on three, one, and one of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). MBIR reconstruction had a significant effect on nine, 11, and 15 of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Of note, the measured size of lung nodules and renal stones with MBIR was significantly different than those for the other two algorithms (P < .002 for all comparisons). Although lesion texture was significantly affected by the

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

PubMed

Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Prevalence, severity, and relationships of lung lesions, liver abnormalities, and rumen health scores measured at slaughter in beef cattle.

PubMed

Rezac, D J; Thomson, D U; Bartle, S J; Osterstock, J B; Prouty, F L; Reinhardt, C D

2014-06-01

An array of management tools exists within the beef industry to improve animal welfare and productivity; however, the ability to assess the outcomes of these tools is needed. Deficiencies in management commonly manifest as bovine respiratory disease complex or nutritional disorders such as acidosis; therefore, lung, liver, and rumen gross pathology lesions present at slaughter were measured as part of the Harvest Audit Program (HAP) and associations with performance determined. Individual gross pathology data from 19,229 cattle at commercial packing plants in Kansas and Texas were collected. Corresponding individual preharvest and carcass data were obtained on a subset of 13,226 cattle. Associations between lesions and performance were modeled using multivariable mixed effect models. Regression coefficients were used for estimation of lesion associative effects on continuous outcomes and odds ratios for dichotomous outcomes. Across the entire population, 67.3% of the cattle had no pulmonary lesions; 22.5 and 9.8% of cattle displayed mild and severe lesions, respectively. Severe pulmonary lesions were associated with a decreased ADG of 0.07 kg and a HCW 7.1 kg less than cohorts with no pulmonary lesions (P < 0.01). Overall, 68.6% of cattle observed had normal livers. Of cattle severely affected by liver abscesses (A+; 4.6%), 14.9% also displayed severe pulmonary lesions and 28.3% displayed mild pulmonary lesions. Rumenitis lesions were observed in 24.1% of the overall study population. Of cattle with mildly abscessed livers (A-), moderately abscessed livers (A), and severely abscessed livers, 20.6, 21.6, and 9.24% displayed mild or severe rumenitis lesions at slaughter. Severe rumenitis lesions were associated with a significant decrease in ADG and HCW (0.025 and 2.20 kg, respectively; P < 0.001). Although the majority of the cattle in this population would be considered low risk, after adjustments for cattle with multiple lesions, 22.9% of cattle in the overall

Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation: an ex-vivo pilot experimental study in animal models.

PubMed

Lamonaca, Vincenzo; Virga, Antonino; Minervini, Marta Ida; Di Stefano, Roberta; Provenzani, Alessio; Tagliareni, Pietro; Fleres, Giovanna; Luca, Angelo; Vizzini, Giovanni; Palazzo, Ugo; Gridelli, Bruno

2009-07-14

To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs). Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80 degrees C, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts. RTA appears to be very effective in killing hydatid cysts of explanted liver and lung. Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration, injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.

Fulminant abdominal gas gangrene in metastatic colon cancer.

PubMed

Bozkurt, Mustafa; Okutur, Kerem; Aydin, Kübra; Namal, Esat; Oztürk, Akin; Balci, Cem; Demir, Gökhan

2012-02-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms.

Vegetable and fruit juice enhances antioxidant capacity and regulates antioxidant gene expression in rat liver, brain and colon

PubMed Central

Yuan, Linhong; Liu, Jinmeng; Zhen, Jie; Xu, Yao; Chen, Shuying; Halm-Lutterodt, Nicholas Van; Xiao, Rong

2017-01-01

Abstract To explore the effect of fruit and vegetable (FV) juice on biomarkers of oxidative damage and antioxidant gene expression in rats, 36 adult male Wistar rats were randomly divided into control, low FV juice dosage or high FV juice dosage treatment groups. The rats were given freshly extracted FV juice or the same volume of saline water daily for five weeks. After intervention, serum and tissues specimens were collected for biomarker and gene expression measurement. FV juice intervention increased total antioxidant capacity, glutathione, vitamin C, β-carotene, total polyphenols, flavonoids levels andglutathione peroxidaseenzyme activity in rat serum or tissues (p < 0.05). FV juice intervention caused reduction of malondialdehyde levels in rat liver (p < 0.05) and significantly modulated transcript levels of glutamate cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase l (NQO1)in rat liver and brain (p < 0.05). The results underline the potential of FV juice to improve the antioxidant capacity and to prevent the oxidative damage in liver, brain and colon. PMID:28323302

Volvulus of the liver with intrathoracic herniation.

PubMed

Moussa, G; Thomson, P M; Bohra, A

2014-10-01

We present a rare case of a liver volvulus, stomach and transverse colon herniating through the diaphragm. This scenario has not been reported previously. We discuss the presentation and management of this interesting case. A 65-year-old woman with a history of sarcoidosis and recurrent pericardial effusions, treated previously with a subxiphoid pericardial oval window fenestration, presented with acute upper abdominal pain radiating to the chest. High contrast computed tomography showed a volvulus of the liver with consequent venous congestion, and herniation of the liver, stomach and transverse colon through an anterior diaphragmatic defect. With liver perfusion threatened, an urgent laparoscopic repair was performed. The stomach and transverse colon were reduced, and the twisted left lobe of the liver was unrotated and reduced into the abdominal cavity. A double-sided synthetic mesh was used to repair the defect. The patient made an uneventful recovery. This is a novel complication of a patient presenting with abdominal pain with a previous history of pericardial window fenestration. A laparoscopic reduction and repair can be performed safely with excellent postoperative results.

The infiltration of experimentally induced lung metastases of colon carcinoma CC531 by adoptively transferred interleukin-2-activated natural killer cells in Wag rats.

PubMed

Kuppen, P J; Basse, P H; Goldfarb, R H; Van De Velde, C J; Fleuren, G J; Eggermont, A M

1994-02-15

The number of IL-2-activated natural killer (A-NK) cells reaching the tumor site in vivo may be crucial for their anti-tumor effect following adoptive immunotherapy. We investigated in a syngeneic rat model the infiltration of established lung metastases by adoptively transferred A-NK cells. The Wag rat colon carcinoma CC531 was injected via a tail vein to induce pulmonary metastases. Syngeneic A-NK cells were labeled with the fluorescent dye rhodamine (TRITC) and next injected via a tail vein in rats bearing day-12 lung tumors. The number of A-NK cells in tumor and in normal tissue per rat was counted in sections after administration of A-NK cells. At all time points tested, a significant linear relationship between the cross-section area of the tumor and the number of infiltrating cells was observed, but small tumor areas became fully infiltrated earlier than larger areas. At 24 hr after injection, approximately 10% of the injected cells were found in the tumor tissue and the average A-NK-cell-to-tumor-cell ratio was estimated to be 1:3. A-NK cells were found in the liver too, although the number of cells per mm2 tissue was low compared with the pulmonary tumor tissue. Very low numbers of A-NK cells were found in kidney, adrenal gland, spleen, and blood. We conclude that, in this syngeneic rat model, adoptively transferred A-NK cells are able to find and specifically infiltrate pulmonary metastases in a time-dependent fashion.

Lipidomic Perturbations in Lung, Kidney, and Liver Tissues of p53 Knockout Mice Analyzed by Nanoflow UPLC-ESI-MS/MS.

PubMed

Park, Se Mi; Byeon, Seul Kee; Sung, Hyerim; Cho, Soo Young; Seong, Je Kyung; Moon, Myeong Hee

2016-10-07

Lipids are important signaling molecules regulating biological processes under normal and diseased conditions. Although p53 mutation is well-known for causing cancer, the relationship between p53-related tumorigenesis and altered lipid profile is unclear. We profiled differences in lipid expressions in liver, lung, and kidney in p53 knockout (KO) mice by high-speed quantitative analysis of 320 lipids (399 species identified) using nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUPLC-MS/MS). Lung tissues were most severely affected by the lack of p53 gene, as shown by significant reduction (24-44%, P < 0.05) in total phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG), and significant increases (30-50%) in phosphatidylserine (PS), phosphatidylinositol (PI), and monohexosylceramide (MHC). MHC levels increased in all tissues. Dihexosylceramide (DHC) level decreased only in kidney tissue. Most PI, PS, and phosphatidic acid (PA) species showing significant increases contained a saturated acyl chain (18:0) in lung and liver tissues. Neutral glycerolipids (16:0/22:0-DG and most TGs with saturated and monounsaturated acyl chains) decreased 2-4-fold in the liver tissue. Our results suggest that the lack of p53 and altered lipid profiles are closely related, but as their changes vary from one tissue to another, the lipid alterations are tissue-specific.

Fulminant abdominal gas gangrene in metastatic colon cancer

PubMed Central

BOZKURT, MUSTAFA; OKUTUR, KEREM; AYDIN, KÜBRA; NAMAL, ESAT; ÖZTÜRK, AKIN; BALCI, CEM; DEMIR, GÖKHAN

2012-01-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms. PMID:22740933

Liver Transplantation and Gut Microbiota Profiling in a Child Colonized by a Multi-Drug Resistant Klebsiella pneumoniae: A New Approach to Move from Antibiotic to "Eubiotic" Control of Microbial Resistance.

PubMed

Del Chierico, Federica; Cardile, Sabrina; Pietrobattista, Andrea; Liccardo, Daniela; Russo, Alessandra; Candusso, Manila; Basso, Maria Sole; Grimaldi, Chiara; Pansani, Laura; Bernaschi, Paola; Torre, Giuliano; Putignani, Lorenza

2018-04-25

The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.

Microbiota and the liver.

PubMed

Shen, Ting-Chin David; Pyrsopoulos, Nikolaos; Rustgi, Vinod K

2018-04-01

The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

In vitro covalent binding of new brain tracer, para-125I-amphetamine, to rat liver and lung microsomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joulin, Y.; Delaforge, M.; Hoellinger, H.

1990-01-01

p-125I-amphetamine (I-Amp) is retained significantly in liver and lung during brain tomoscintigraphy. To attempt to explain this clinical observation, we have investigated the interaction of I-Amp with rat liver and lung microsomal proteins. Studies using spectral shift technique indicate that low concentration of I-Amp gives a type I complex and high concentration appears very stable type II complex with cytochrome P-450 Fe III. In the presence of NADPH, I-Amp gives rise to a 455 nm absorbing complex with similar properties to the Fe-RNO complexes. This complex formation was greatly enhanced with phenobarbital treated liver microsomes. The in vitro binding studymore » shows that I-Amp and/or its metabolites was covalently bound to macromolecules in the presence of the molecular oxygen and NADPH-generating system. Incubation in the presence of glutathione, cystein and radical scavengers decreases binding. Mixed function oxydase (MFO) inhibitors diminish the amount of covalent binding and alter the extent of metabolite formation. The total covalent binding level increased with liver microsomes from PB pretreated rats as it was observed with the 455nm complex formation. The radioactivity distribution on microsomal proteins was examinated with SDS polyacrylamide gel electrophoresis and autoradiography. This experiment proves that the radiolabelled compounds are bound on the cytochrome P-450. The radioactivity bound increased when the PB induced rat liver microsomes were used. All these results indicate that I-Amp was activated by an oxydative process dependent on the MFO system which suggests a N-oxydation of I-Amp and the formation of reactive entities which covalently bind to proteins.« less

Polyethylene Glycol (PEG) Linked to Near Infrared (NIR) Dyes Conjugated to Chimeric Anti-Carcinoembryonic Antigen (CEA) Antibody Enhances Imaging of Liver Metastases in a Nude-Mouse Model of Human Colon Cancer

PubMed Central

Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2014-01-01

We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases. PMID:24859320

MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease.

PubMed

Rips, Jonathan; Meyer-Schuman, Rebecca; Breuer, Oded; Tsabari, Reuven; Shaag, Avraham; Revel-Vilk, Shoshana; Reif, Shimon; Elpeleg, Orly; Antonellis, Anthony; Harel, Tamar

2018-04-12

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNA with cognate amino acids during protein translation. Non-canonical functions are increasingly recognized, and include transcription and translation control and extracellular signaling. Monoallelic mutations in genes encoding several ARSs have been identified in axonal Charcot-Marie-Tooth (CMT2) disease, whereas biallelic mutations in ARS loci have been associated with multi-tissue syndromes, variably involving the central nervous system, lung, and liver. We report a male infant of non-consanguineous origin, presenting with successive onset of transfusion-dependent anemia, hypothyroidism, cholestasis, interstitial lung disease, and developmental delay. Whole-exome sequencing (WES) revealed compound heterozygosity for two variants (p.Tyr307Cys and p.Arg618Cys) in MARS, encoding methionyl-tRNA synthetase. Biallelic MARS mutations are associated with interstitial lung and liver disease (ILLD). Interestingly, the p.Arg618Cys variant, inherited from an unaffected father, was previously reported in a family with autosomal dominant late-onset CMT2. Yeast complementation assays confirmed pathogenicity of p.Arg618Cys, yet suggested retained function of p.Tyr307Cys. Our findings underscore the phenotypic variability associated with ARS mutations, and suggest genetic or environmental modifying factors in the onset of monoallelic MARS-associated CMT2. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Could JC virus provoke metastasis in colon cancer?

PubMed Central

Sinagra, Emanuele; Raimondo, Dario; Gallo, Elena; Stella, Mario; Cottone, Mario; Orlando, Ambrogio; Rossi, Francesca; Orlando, Emanuele; Messina, Marco; Tomasello, Giovanni; Lo Monte, Attilio Ignazio; La Rocca, Ennio; Rizzo, Aroldo Gabriele

2014-01-01

AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test. RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ2 = 9.55, P = 0.002). CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors. PMID:25400458

Direction-dependent regularization for improved estimation of liver and lung motion in 4D image data

NASA Astrophysics Data System (ADS)

Schmidt-Richberg, Alexander; Ehrhardt, Jan; Werner, René; Handels, Heinz

2010-03-01

The estimation of respiratory motion is a fundamental requisite for many applications in the field of 4D medical imaging, for example for radiotherapy of thoracic and abdominal tumors. It is usually done using non-linear registration of time frames of the sequence without further modelling of physiological motion properties. In this context, the accurate calculation of liver und lung motion is especially challenging because the organs are slipping along the surrounding tissue (i.e. the rib cage) during the respiratory cycle, which leads to discontinuities in the motion field. Without incorporating this specific physiological characteristic, common smoothing mechanisms cause an incorrect estimation along the object borders. In this paper, we present an extended diffusion-based model for incorporating physiological knowledge in image registration. By decoupling normal- and tangential-directed smoothing, we are able to estimate slipping motion at the organ borders while preventing gaps and ensuring smooth motion fields inside. We evaluate our model for the estimation of lung and liver motion on the basis of publicly accessible 4D CT and 4D MRI data. The results show a considerable increase of registration accuracy with respect to the target registration error and a more plausible motion estimation.

Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCallum, Gordon P.; Siu, Michelle; Sweeting, J. Nicole

2011-01-15

In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 micemore » with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.« less

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souza, Lucas E.B., E-mail: lucasebsouza@usp.br; Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP; Almeida, Danilo C., E-mail: gudaalmeida@gmail.com

The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice weremore » subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM

Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum coinfection after lung and liver transplantation in a cystic fibrosis patient.

PubMed

Hirschi, Sandrine; Letscher-Bru, Valérie; Pottecher, Julien; Lannes, Béatrice; Jeung, Mi Young; Degot, Tristan; Santelmo, Nicola; Sabou, Alina Marcela; Herbrecht, Raoul; Kessler, Romain

2012-12-01

Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient.

[Overexpression of liver kinase B1 inhibits the proliferation of lung cancer cells].

PubMed

Li, Yang; Zhang, Libin; Wang, Ping

2017-01-01

Objective To explore the effect of overexpressed liver kinase B1(LKB1) on the proliferation of lung cancer cell lines. Methods The expression levels of LKB1 and PTEN in A549, NCI-H23, NCI-H157, XWLC-05, NCI-H446 lung cancer cells were detected by immunocytochemistry (ICC) and Western blotting. Plasmid pcDNA3.1 + -LKB1 and empty vector pcDNA3.1 + -null were separately transfected into the above five cell lines, and then the expression of LKB1 mRNA and protein were determined by quantitative real-time PCR and Western blotting, respectively. Finally, CCK-8 assay was used to analyze the proliferation ability of the transfected cells. Results LKB1 and PTEN were positive in NCI-H23 cells; LKB1 was negative while PTEN was positive in A549 and NCI-H446 cells; both LKB1 and PTEN were negative in NCI-H157 and XWLC-05 cells. Quantitative real-time PCR and Western blotting showed that the expression level of LKB1 significantly increased in the above cell lines transfected with plasmid pcDNA3.1 + -LKB1 compared with the ones with empty vector pcDNA3.1 + -null. Besides, CCK-8 assay showed that the overexpression of LKB1 in the lung cancer cells transfected with pcDNA3.1 + -LKB1 had an obvious inhibitory effect on cell proliferation. Conclusion The expression of LKB1 is down-regulated in most of the lung cell lines to different extent and the over-expression of LKB1 can remarkably inhibit the proliferation ability of lung cancer cell lines.

Oxidative Stress, Inflammatory Biomarkers, and Toxicity in Mouse Lung and Liver After Inhalation Exposure to 100% Biodiesel or Petroleum Diesel Emissions

PubMed Central

Shvedova, Anna A.; Yanamala, Naveena; Murray, Ashley R.; Kisin, Elena R.; Khaliullin, Timur; Hatfield, Meghan K.; Tkach, Alexey V.; Krantz, Q. T.; Nash, David; King, Charly; Gilmour, M. Ian; Gavett, Stephen H.

2015-01-01

Over the past decade, soy biodiesel (BD) has become a first alternative energy source that is economically viable and meets requirements of the Clean Air Act. Due to lower mass emissions and reduced hazardous compounds compared to diesel combustion emissions (CE), BD exposure is proposed to produce fewer adverse health effects. However, considering the broad use of BD and its blends in different industries, this assertion needs to be supported and validated by mechanistic and toxicological data. Here, adverse effects were compared in lungs and liver of BALB/cJ mice after inhalation exposure (0, 50, 150, or 500 μg/m3; 4 h/d, 5 d/wk, for 4 wk) to CE from 100% biodiesel (B100) and diesel (D100). Compared to D100, B100 CE produced a significant accumulation of oxidatively modified proteins (carbonyls), an increase in 4-hydroxynonenal (4-HNE), a reduction of protein thiols, a depletion of antioxidant gluthatione (GSH), a dose-related rise in the levels of biomarkers of tissue damage (lactate dehydrogenase, LDH) in lungs, and inflammation (myeloperoxidase, MPO) in both lungs and liver. Significant differences in the levels of inflammatory cytokines interleukin (IL)-6, IL-10, IL-12p70, monocyte chemoattractant protein (MCP)-1, interferon (IFN) γ, and tumor necrosis factor (TNF)-α were detected in lungs and liver upon B100 and D100 CE exposures. Overall, the tissue damage, oxidative stress, inflammation, and cytokine response were more pronounced in mice exposed to BD CE. Further studies are required to understand what combustion products in BD CE accelerate oxidative and inflammatory responses. PMID:24156694

[1990-1996: the experience of the La Fe Lung Transplant Group (Valencia)].

PubMed

Borro Maté, J M; Morales Marín, P; Lozano Ruiz, C; Tarrazona Hervás, V; Galán Gil, G; Calvo Medina, V; Morant Guillén, P; Ramos Briones, F; Vicente Guillén, R; Paris Romeu, F

1997-10-01

Objective to review the experience of the lung transplantation unit at Hospital La Fe (Valencia). Between February 1990 and March 1996 we performed 40 lung transplants. The following causes were most common: cystic fibrosis (9 cases), emphysema (8), pulmonary fibrosis (8) and bronchiectasis (7). Types of intervention were 27 double lung transplants (25 sequential and 9 blocked), 9 single lung transplants, and 4 heart-lung transplants. We then reviewed the 36 single and double lung transplants. The main exclusion criteria were age over 65 years, malignant disease, kidney or liver disease, severe or non reversible central nervous system disease, and drug addiction. Prior surgery, mechanical ventilation and the presence of Aspergillus were considered lower-order contraindications. Mean patient age was 37.7 years (14-59). Six patients were colonized by Aspergillus before transplantation. Five had undergone earlier surgery and two were mechanically ventilated before the transplant. The most common complication was respiratory infection, which was present in 6 of the 7 patients who died. Other complications in order of frequency were dehiscence and/or bronchial stenosis, corticoid myopathy and postoperative bleeding. The actuarial survival rate of single and double lung transplants was 67.85 after 3 years, and 87.5% in patients with cystic fibrosis. Lung transplantation is a well-established procedure that is gradually being extended to treat more conditions. The main obstacle is the scarcity of donors. The main challenge at present is bronchiolitis obliterans.

A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

PubMed

Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

2014-06-01

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib.

PubMed

Zhu, Zhouyu; Chai, Ying

2016-11-01

A 65-year-old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Selective reconstitution of liver cholesterol biosynthesis promotes lung maturation but does not prevent neonatal lethality in Dhcr7 null mice.

PubMed

Yu, Hongwei; Li, Man; Tint, G Stephen; Chen, Jianliang; Xu, Guorong; Patel, Shailendra B

2007-04-04

Targeted disruption of the murine 3beta-hydroxysterol-Delta7-reductase gene (Dhcr7), an animal model of Smith-Lemli-Opitz syndrome, leads to loss of cholesterol synthesis and neonatal death that can be partially rescued by transgenic replacement of DHCR7 expression in brain during embryogenesis. To gain further insight into the role of non-brain tissue cholesterol deficiency in the pathophysiology, we tested whether the lethal phenotype could be abrogated by selective transgenic complementation with DHCR7 expression in the liver. We generated mice that carried a liver-specific human DHCR7 transgene whose expression was driven by the human apolipoprotein E (ApoE) promoter and its associated liver-specific enhancer. These mice were then crossed with Dhcr7+/- mutants to generate Dhcr7-/- mice bearing a human DHCR7 transgene. Robust hepatic transgene expression resulted in significant improvement of cholesterol homeostasis with cholesterol concentrations increasing to 80~90 % of normal levels in liver and lung. Significantly, cholesterol deficiency in brain was not altered. Although late gestational lung sacculation defect reported previously was significantly improved, there was no parallel increase in postnatal survival in the transgenic mutant mice. The reconstitution of DHCR7 function selectively in liver induced a significant improvement of cholesterol homeostasis in non-brain tissues, but failed to rescue the neonatal lethality of Dhcr7 null mice. These results provided further evidence that CNS defects caused by Dhcr7 null likely play a major role in the lethal pathogenesis of Dhcr7-/- mice, with the peripheral organs contributing the morbidity.

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

PubMed

Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

2018-06-01

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts

PubMed Central

Li, Jun; Wu, Chuanchuan; Wang, Hui; Liu, Huanyuan; Vuitton, Dominique A.; Wen, Hao; Zhang, Wenbao

2014-01-01

Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis. PMID:25456565

Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae.

PubMed

Urb, Mirjam; Snarr, Brendan D; Wojewodka, Gabriella; Lehoux, Mélanie; Lee, Mark J; Ralph, Benjamin; Divangahi, Maziar; King, Irah L; McGovern, Toby K; Martin, James G; Fraser, Richard; Radzioch, Danuta; Sheppard, Donald C

2015-09-01

Airway colonization by the mold Aspergillus fumigatus is common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization with A. fumigatus hyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established an in vivo model to study the natural history of airway colonization with live A. fumigatus hyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4(+) T cells, followed by a rise in IL-17 and Foxp3(+) cells by day 14. These results provide the first report of the evolution of the immune response to A. fumigatus hyphal colonization. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Vaccine Therapy and Sargramostim With or Without Docetaxel in Treating Patients With Metastatic Lung Cancer or Metastatic Colorectal Cancer

ClinicalTrials.gov

2014-03-28

Extensive Stage Small Cell Lung Cancer; Recurrent Colon Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Rectal Cancer; Recurrent Small Cell Lung Cancer; Stage IV Colon Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Rectal Cancer

Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China.

PubMed

Zhao, Jin-Kou; Wu, Ming; Kim, Claire H; Jin, Zi-Yi; Zhou, Jin-Yi; Han, Ren-Qiang; Yang, Jie; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Gu, Xiaoping; Su, Ming; Hu, Xu; Sun, Zheng; Li, Gang; Li, Liming; Mu, Lina; Zhang, Zuo-Feng

2017-07-01

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

PubMed

Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien

2013-09-01

To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

Colonization with Small Conidia Aspergillus Species is associated with Bronchiolitis Obliterans Syndrome: A Two-Center Validation Study

PubMed Central

Weigt, S. Sam; Copeland, C. Ashley Finlen; Derhovanessian, Ariss; Shino, Michael Y.; Davis, W. Austin; Snyder, Laurie D.; Saggar, Rajan; Lynch, Joseph P.; Ross, David J.; Ardehali, Abbas; Elashoff, Robert M.; Palmer, Scott M.; Belperio, John A.

2012-01-01

Aspergillus colonization after lung transplantation may increase the risk for bronchiolitis obliterans syndrome (BOS), a disease of small airways. We hypothesized that colonization with small conidia Aspergillus species would be associated with a greater risk of BOS, based upon an increased likelihood of deposition in small airways. We studied adult primary lung recipients from two large centers; 298 recipients at University of California, Los Angeles and 482 recipients at Duke University Medical Center. We grouped Aspergillus species by conidia diameter ≤3.5μm. We assessed the relationship of colonization with outcomes in Cox models. Pre-BOS colonization with small conidia Aspergillus species, but not large, was a risk factor for BOS (P = 0.002, HR 1.44, 95% CI 1.14–1.82), along with acute rejection, single lung, and Pseudomonas. Colonization with small conidia species also associated with risk of death (P = 0.03, HR 1.30, 95% CI 1.03–1.64). Although other virulence traits besides conidia size may be important, we have demonstrated in two large independent cohorts that colonization with small conidia Aspergillus species increases the risk of BOS and death. Prospective evaluation of strategies to prevent Aspergillus colonization of small airways is warranted, with the goal of preserving lung allograft function as long as possible. PMID:23398785

The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases.

PubMed

Zeelenberg, Ingrid S; Ruuls-Van Stalle, Lisette; Roos, Ed

2003-07-01

CXCR4, the receptor for the chemokine stromal cell-derived factor (SDF)-1 (CXCL12), is involved in lymphocyte trafficking. We have demonstrated previously that it is required for invasion of lymphoma cells into tissues and therefore essential for lymphoma metastasis. CXCR4 is also expressed by carcinoma cells, and CXCR4 antibodies were recently shown to reduce metastasis of a mammary carcinoma cell line. This was also ascribed to impaired invasion. We have blocked CXCR4 function in CT-26 colon carcinoma cells by transfection of SDF-1, extended with a KDEL sequence. The SDF-KDEL protein is retained in the endoplasmic reticulum by the KDEL-receptor and binds CXCR4, which is thus prevented from reaching the cell surface. We found that metastasis of these cells to liver and lungs was greatly reduced and often completely blocked. Surprisingly, however, our observations indicate that this was not attributable to inhibition of invasion but rather to impairment of outgrowth of micrometastases: (a) in contrast to the lymphoma cells, metastasis was not affected by the transfected S1 subunit of pertussis toxin. S1 completely inhibited Gi protein signaling, which is required for SDF-1-induced invasion; (b) CXCR4 levels were very low in CT-26 cells grown in vitro but strongly up-regulated in vivo. Strong up-regulation was not seen in the lungs until 7 days after tail vein injection. CXCR4 can thus have no role in initial invasion in the lungs; and (c) CXCR4-deficient cells did colonize the lungs to the same extent as control cells and survived. However, they did not expand, whereas control cells proliferated rapidly after a lag period of > or = 7 days. We conclude that CXCR4 is up-regulated by the microenvironment and that isolated metastatic cells are likely to require CXCR4 signals to initiate proliferation. Our results suggest that CXCR4 inhibitors have potential as anticancer agents to suppress outgrowth of micrometastases.

Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma.

PubMed

Son, Seung Hwa; Park, Kwang-Kyun; Park, Sun Kyu; Kim, Young Choong; Kim, Yeong Shik; Lee, Sang-Kook; Chung, Won-Yoon

2011-07-01

The principal objective of the present study was to evaluate the antimetastatic activity of decursin and decursinol isolated from Angelica gigas. Decursin and decursinol inhibited the proliferation and invasion of CT-26 colon carcinoma cells. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in cells and the activities in the culture medium were also reduced by decursin and decursinol treatment. In CT-26 cells, the extracellular signal-regulated kinase (ERK) inhibitor inhibited cell proliferation, invasion and MMP-9 expression, and the c-Jun N-terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as well as cell proliferation and cell invasion. The phosphatidylinositol-3 kinase (PI3K) inhibitor reduced only the expression of MMP-2. In addition, the invasion of CT-26 cells was inhibited by the treatment with anti-MMP-9 antibody, rather than anti-MMP-2 antibody. These results indicate that MMP-9 expression via ERK and JNK plays a critical role for the invasion of CT26 cells. Decursin and decursinol downregulated ERK and JNK phosphorylation. Moreover, oral administration of decursin and decursinol reduced the formation of tumor nodules in the lungs and the increase in lung weight caused by CT-26 metastases. Therefore, both decursin and decursinol may be beneficial antimetastatic agents, targeting MMPs and their upstream signaling molecules. Copyright © 2011 John Wiley & Sons, Ltd.

Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

PubMed

Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

2016-04-01

Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

Phylogenetic characterization of a novel herpesvirus found in the liver and lungs of a Chilean flamingo (Phoenicopterus chilensis).

PubMed

Coverdill, Christopher C; Barnes, Julie A; Garner, Michael M; Hinton, Kevin L; Childress, April L; Wellehan, James F X

2016-05-01

A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in California. Postmortem examination identified a pale, enlarged liver, mildly increased fluid in the lungs, and red foci in the spleen. Histologic examination revealed marked hepatic necrosis with syncytia, splenic necrosis, and interstitial pneumonia with eosinophilic intranuclear inclusions within hepatocytes and in unidentified cells of the lung. Transmission electron microscopy identified virions consistent with a herpesvirus in the nucleus and cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus in the subfamily Alphaherpesvirinae. © 2016 The Author(s).

[Effects of Feiji decoction for soothing the liver combined with psychotherapy on quality of life in primary lung cancer patients].

PubMed

Yao, Yilin

2012-01-01

Primary lung cancer is one of the most common malignant tumors. It causes great pain and mood disorders to patients, and significantly reduces their quality of life. The aim of the current study is to evaluate the effect of Feiji Decoction for soothing the liver combined with psychotherapy on quality of life (QoL) and physical status of patients with primary lung cancer. A total of 118 patients with primary non-small cell lung cancer were randomly divided into two groups. The 57 patients in the combined therapy group were treated with Feiji Decoction for soothing the liver and psychotherapy combined with chemotherapy, whereas the 61 patients in the control group were treated with chemotherapy only. Both groups were observed for the two treatment courses. The European Organization for Research and Treatment of Cancer QoL Questionnaire LC-43 (EORTC QLQ-LC43) was used to assess the QoL of every patient in both groups before and after treatment scales. At the same time, physical status was assessed using the Karnofsky performance status (KPS) and East Cooperative Oncology Group performance status (ECOG). The scores of physiology function, role function, emotion function, cognize function, society function, and general health in the therapy group were higher than that of the control group. The therapy group also showed better QoL results than the contol group. Significant differences were observed between the two groups (P<0.01). Meanwhile, the scores of fatigue, vomit, pain, polypnea, insomnia, anorexia, constipation, and specific manifestation of lung cancer in the therapy group were obviously lower than that of the control group; more patients were observed to be relieved. Significant differences between the two groups were observed (P<0.01). The KPS and ECOG scores of the patients were observed to have improved and stabilized in the therapy group than that of the control group; the differences were statistically significant (P<0.01). Feiji Decoction for soothing the

Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts.

PubMed

Li, Jun; Wu, Chuanchuan; Wang, Hui; Liu, Huanyuan; Vuitton, Dominique A; Wen, Hao; Zhang, Wenbao

2014-01-01

Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis. © J. Li et al., published by EDP Sciences, 2014.

Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

PubMed

Velázquez, Kandy T; Enos, Reilly T; Carson, Meredith S; Cranford, Taryn L; Bader, Jackie E; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi; Davis, J Mark; Carson, James A; Murphy, E Angela

2016-10-01

Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80 + CD206 + macrophages and activated T cells (CD4 + CD69 + ) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms. Copyright © 2016 the American Physiological Society.

Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B{sub 1} and its dependence on p53 genotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulder, Jeanne E.; Bondy, Genevieve S.; Mehta, Rekha

Aflatoxin B{sub 1} (AFB{sub 1}) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53{sup tm1Brd}N5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB{sub 1} for 26 weeks. NER activity was assessed with an in vitro assay, using AFB{sub 1}-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB{sub 1}–N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposedmore » to 0.2 ppm and 1.0 ppm AFB{sub 1} respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05). In heterozygous p53 knockout mice, repair of AFB{sub 1}–N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB{sub 1} or in liver extracts from mice treated with either AFB{sub 1} concentration. p53 genotype did not affect basal levels of repair. AFB{sub 1} exposure did not alter repair of AFB{sub 1}-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB{sub 1} increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage. - Highlights: • Mice are chronically exposed to low doses of the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}). • The effects of AFB{sub 1} and p53 status on nucleotide excision repair are investigated. • AFB{sub 1} increases nucleotide excision repair in wild type mouse lung and liver. • This increase is attenuated in p53 heterozygous mouse lung and liver. • Results portray the role of p53 in

Pyogenic liver abscess presenting after malignant polypectomy.

PubMed

Harnik, Ian G

2007-12-01

Streptococcus bovis bacteremia has been linked to the presence of occult colon cancer since 1977. We present a case of pyogenic liver abscess and bacteremia with a different Streptococcus viridans 1 week after colonic adenocarcinoma was removed via polypectomy, discuss the likely etiology and review whether there is evidence to support looking for colon cancer in patients who present similarly but have not already undergone screening.

Liver biopsy

MedlinePlus

... Primary biliary cirrhosis Primary biliary cholangitis Pyogenic liver abscess Reye syndrome Sclerosing cholangitis Wilson disease Risks Risks may include: Collapsed lung Complications from the sedation Injury to the gallbladder ...

Lung Cancer Trends

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Trends for Other Kinds of Cancer Breast Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend ...

[Lung transplant therapy for suppurative diseases].

PubMed

de Pablo, A; López, S; Ussetti, P; Carreño, M C; Laporta, R; López García-Gallo, C; Ferreiro, M J

2005-05-01

Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. Although airway colonization in patients with suppurative diseases complicates postoperative management

Suppression of Angiogenesis and Therapy of Human Colon Cancer Liver Metastasis by Systemic Administration of Interferon-α1

PubMed Central

Ozawa, Shutaro; Shinohara, Hisashi; Kanayama, Hiro-omi; Bruns, Christiane J; Bucana, Corazon D; Ellis, Lee M; Davis, Darren W; Fidler, Isaiah J

2001-01-01

Abstract The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive) or KM12L4 IFNR (IFN-α-resistant) cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c.) injections of IFN-α (70,000 units/week) at different dosing schedules (1, 2, or 7 times/week). Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF) or matrix metalloproteinase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis-associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α-2a depends on frequent administration of the optimal biologic dose. PMID:11420751

Zika Virus Alters the Expression Profile of microRNA-Related Genes in Liver, Lung, and Kidney Cell Lineages.

PubMed

Ferreira, Rafaella Nascimento; Holanda, Gustavo Moraes; Pinto Silva, Eliana Vieira; Casseb, Samir Mansour Moraes; Melo, Karla Fabiane Lopes; Carvalho, Carlos Alberto Marques; Lima, Juliana Abreu; Vasconcelos, Pedro Fernando Costa; Cruz, Ana Cecília Ribeiro

2018-06-07

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (Flaviviridae). ZIKV infection is associated with alterations in various organs, including the liver, lungs, and kidneys. Studies on the influence of posttranscriptional control on viral infections have demonstrated that microRNAs (miRNAs) interfere with different stages of the replicative cycle of several viruses and may influence the disease outcome. To shed light on ZIKV-induced regulation of host miRNA-processing machinery in the above organs, we analyzed the expression of genes encoding key proteins of the miRNA pathway in different ZIKV-infected continuous primate cell lineages (HepG2, A549, and MA104) by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Expression of the genes encoding the miRNA-related proteins DGCR8, Ago1, and Ago3 in HepG2 cells and Drosha, Dicer, Ago2, and Ago3 in A549 and MA104 cells was significantly altered in the presence of ZIKV. Our results suggest that ZIKV modulates miRNA levels during infection in liver, lung, and kidney cells, which may be an additional mechanism of host cell subversion in these organs.

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib

PubMed Central

Zhu, Zhouyu

2016-01-01

A 65‐year‐old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. PMID:27807951

Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer.

PubMed Central

Isidoro, Antonio; Martínez, Marta; Fernández, Pedro L; Ortega, Alvaro D; Santamaría, Gema; Chamorro, Margarita; Reed, John C; Cuezva, José M

2004-01-01

Recent findings indicate that the expression of the beta-catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is depressed in liver, kidney and colon carcinomas, providing further a bioenergetic signature of cancer that is associated with patient survival. In the present study, we performed an analysis of mitochondrial and glycolytic protein markers in breast, gastric and prostate adenocarcinomas, and in squamous oesophageal and lung carcinomas. The expression of mitochondrial and glycolytic markers varied significantly in these carcinomas, when compared with paired normal tissues, with the exception of prostate cancer. Overall, the relative expression of beta-F1-ATPase was significantly reduced in breast and gastric adenocarcinomas, as well as in squamous oesophageal and lung carcinomas, strongly suggesting that alteration of the bioenergetic function of mitochondria is a hallmark of these types of cancer. PMID:14683524

The xanthine oxidase inhibitor Febuxostat reduces tissue uric acid content and inhibits injury-induced inflammation in the liver and lung

PubMed Central

Kataoka, Hiroshi; Yang, Ke; Rock, Kenneth L.

2014-01-01

Necrotic cell death in vivo induces a robust neutrophilic inflammatory response and the resulting inflammation can cause further tissue damage and disease. Dying cells induce this inflammation by releasing pro-inflammatory intracellular components, one of which is uric acid. Cells contain high levels of intracellular uric acid, which is produced when purines are oxidized by the enzyme xanthine oxidase. Here we test whether a non-nucleoside xanthine oxidase inhibitor, Febuxostat (FBX), can reduce intracellular uric acid levels and inhibit cell death-induced inflammation in two different murine tissue injury models; acid-induced acute lung injury and acetaminophen liver injury. Infiltration of inflammatory cells induced by acid injection into lungs or peritoneal administration of acetaminophen was evaluated by quantification with flow cytometry and tissue myeloperoxidase activity in the presence or absence of FBX treatment. Uric acid levels in serum and tissue were measured before giving the stimuli and during inflammation. The impact of FBX treatment on the peritoneal inflammation caused by the microbial stimulus, zymosan, was also analyzed to see whether FBX had a broad anti-inflammatory effect. We found that FBX reduced uric acid levels in acid-injured lung tissue and inhibited acute pulmonary inflammation triggered by lung injury. Similarly, FBX reduced uric acid levels in the liver and inhibited inflammation in response to acetaminophen-induced hepatic injury. In contrast, FBX did not reduce inflammation to zymosan, and therefore is not acting as a general anti-inflammatory agent. These results point to the potential of using agents like FBX to treat cell death-induced inflammation. PMID:25449036

Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-Microspheres Used in Preradioembolization Dosimetry: Influence on the Liver-Lung Shunt.

PubMed

Grosser, Oliver S; Ruf, Juri; Kupitz, Dennis; Pethe, Annette; Ulrich, Gerhard; Genseke, Philipp; Mohnike, Konrad; Pech, Maciej; Richter, Wolf S; Ricke, Jens; Amthauer, Holger

2016-06-01

Perfusion scintigraphy using (99m)Tc-labeled albumin aggregates is mandatory before hepatic radioembolization with (90)Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, (99m)Tc-MAA (macroaggregated serum albumin [MAA]) and (99m)Tc-HSA (human serum albumin [HSA]), was assessed. In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver-lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Compared with (99m)Tc-MAA-microspheres, (99m)Tc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparison of two methods for recovering migrating Ascaris suum larvae from the liver and lungs of pigs.

PubMed

Slotved, H C; Roepstorff, A; Barnes, E H; Eriksen, L; Nansen, P

1996-08-01

Nine groups of 5 pigs were inoculated with Ascaris suum eggs on day 0. Groups 1, 2, and 3 were inoculated with 100 eggs, groups 4, 5, and 6 with 1,000 eggs, and groups 7, 8, and 9 with 10,000 eggs. On day 3, groups 1, 4, and 7 were slaughtered, on day 7 groups 2, 5, and 8, and on day 10 groups 3, 6, and 9. The liver (days 3 and 7) and lungs (days 3, 7, and 10) were removed and 2, 25% samples of both organs were collected. Larvae were recovered from 1 sample by the Baermann method and from the other by an agar-gel method. Overall there were no significant differences in the liver larval recovery between the 2 methods. The use of the agar-gel method resulted in a very clean suspension of larvae and thereby reduced the sample counting time by a factor of 5-10 compared to the Baermann method. With both methods larval recovery from the lungs resulted in a clean larval suspension that was easy to count, and there were overall no significant differences between the 2 methods, although there was a tendency toward the Baermann method recovering more larvae from the lungs than the agar-gel method. The tissue sample dry weight did not significantly influence larval recovery by the agar-gel method, and the time interval from slaughtering to start of incubation on day 3 (interval 51-92 min), day 7 (interval 37-114 min), and day 10 (interval 50-129 min) had no significant effect on recovery by either method.

Induction of Colon Cancer in Mice with 1,2-Dimethylhydrazine.

PubMed

Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2015-09-01

In this protocol, colon cancer is induced in mice through a series of injections with 1,2-dimethylhydrazine. Mice will develop primarily colon tumors starting at about 3 mo after the first injection. Tumors in the lung, uterus, and small intestine may also be seen, as well as lymphomas. © 2015 Cold Spring Harbor Laboratory Press.

Seasonal variations in fine particle composition from Beijing prompt oxidative stress response in mouse lung and liver.

PubMed

Pardo, Michal; Xu, Fanfan; Qiu, Xinghua; Zhu, Tong; Rudich, Yinon

2018-06-01

Exposure to air pollution can induce oxidative stress, inflammation and adverse health effects. To understand how seasonal and chemical variations drive health impacts, we investigated indications for oxidative stress and inflammation in mice exposed to water and organic extracts from urban fine particles/PM 2.5 (particles with aerodynamic diameter ≤ 2.5 μm) collected in Beijing, China. Higher levels of pollution components were detected in heating season (HS, winter and part of spring) PM 2.5 than in the non-heating season (NHS, summer and part of spring and autumn) PM 2.5 . HS samples were high in metals for the water extraction and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction compared to their controls. An increased inflammatory response was detected in the lung and liver following exposure to the organic extracts compared to the water extracts, and mostly in the HS PM 2.5 . While reduced antioxidant response was observed in the lung, it was activated in the liver, again, more in the HS extracts. Nrf2 transcription factor, a master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response, and its related genes were induced. In the liver, elevated levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of cell damage and proliferation, indicating oxidative and toxic damage. In addition, expression of genes related to detoxification of PAHs was observed. Altogether, the study suggests that the acute effects of PM 2.5 can vary seasonally with stronger health effects in the HS than in the NHS in Beijing, China and that some secondary organs may be susceptible for the exposure damage. Specifically, the liver is a potential organ influenced by exposure to organic components such as PAHs from coal or biomass burning and heating. Copyright © 2018 Elsevier B.V. All rights reserved.

Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

PubMed

Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

2018-02-05

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

The utility of micro-CT and MRI in the assessment of longitudinal growth of liver metastases in a preclinical model of colon carcinoma.

PubMed

Pandit, Prachi; Johnston, Samuel M; Qi, Yi; Story, Jennifer; Nelson, Rendon; Johnson, G Allan

2013-04-01

Liver is a common site for distal metastases in colon and rectal cancer. Numerous clinical studies have analyzed the relative merits of different imaging modalities for detection of liver metastases. Several exciting new therapies are being investigated in preclinical models. But, technical challenges in preclinical imaging make it difficult to translate conclusions from clinical studies to the preclinical environment. This study addresses the technical challenges of preclinical magnetic resonance imaging (MRI) and micro-computed tomography (CT) to enable comparison of state-of-the-art methods for following metastatic liver disease. We optimized two promising preclinical protocols to enable a parallel longitudinal study tracking metastatic human colon carcinoma growth in a mouse model: T2-weighted MRI using two-shot PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) and contrast-enhanced micro-CT using a liposomal contrast agent. Both methods were tailored for high throughput with attention to animal support and anesthesia to limit biological stress. Each modality has its strengths. Micro-CT permitted more rapid acquisition (<10 minutes) with the highest spatial resolution (88-micron isotropic resolution). But detection of metastatic lesions requires the use of a blood pool contrast agent, which could introduce a confound in the evaluation of new therapies. MRI was slower (30 minutes) and had lower anisotropic spatial resolution. But MRI eliminates the need for a contrast agent and the contrast-to-noise between tumor and normal parenchyma was higher, making earlier detection of small lesions possible. Both methods supported a relatively high-throughput, longitudinal study of the development of metastatic lesions. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Ractopamine analysis in pig kidney, liver and lungs: A validation of the method scope extension using QuEChERS as a sample preparation step.

PubMed

Feddern, Vivian; Aroeira, Carolina Naves; Molognoni, Luciano; Gressler, Vanessa; Daguer, Heitor; Dalla Costa, Osmar Antonio; Castillo, Carmen Josefina Contreras; de Lima, Gustavo Julio Mello Monteiro

2018-05-23

Ractopamine has been allowed by some countries as a repartitioning additive in pig diet, since it promotes protein synthesis and fat lipolysis. Most regulatory agencies only propose the ractopamine assessment in meat, kidney, liver and fat. Aiming at contributing to the scarcity data regarding this analyte in pig lungs, we extended the scope of a LC-MS method to evaluate pig offals. Homogenized tissue samples were extracted by a QuEChERS procedure; following by clean up steps and further tandem mass spectrometry determination. Method performance was evaluated through specificity, recovery, linearity, reproducibility, repeatability, decision limit (CC α ), and detection capability (CC β ), in accordance to the Commission Decision 2002/657/EC. Regression coefficients (R 2 ) between 0.994 and 0.999 were achieved for kidney, liver and lungs. Recoveries ranged from 92.0 to 127%. CC α and CC β values ranged from 3.65 to 4.86 μg kg -1 , and from 6.27 to 7.21 μg kg -1 , respectively. These values were under the maximum residue limits suggested by Codex Alimentarius, which are 90 and 40 μg kg -1 for kidney and liver, respectively. When applied to real samples up to 22.5, 92 and 1003 μg kg -1 of ractopamine residues were detected in pig liver, kidney and lungs, respectively. The results allowed concluding that the proposed analytical method is capable to detect ractopamine residues in all evaluated matrices. Therefore, it can be successfully applied and used as a routine method in laboratories of residue analysis. Copyright © 2018. Published by Elsevier B.V.

Radioisotope scanning of brain, liver, lung and bone with a note on tumour localizing agents

PubMed Central

Lavender, J. P.

1973-01-01

Radioisotopic scanning of brain, liver, lungs and the skeleton is briefly reviewed with a survey of recent developments of clinical significance. In brain scanning neoplasm detection rates of greater than 90% are claimed. The true figure is probably 70-80%. Autopsy data shows a number of false negatives, particularly with vascular lesions. Attempts to make scanning more specific in differentiating neoplasm from vascular lesions by rapid sequence blood flow studies are reviewed. In liver scanning by means of colloids again high success rate is claimed but small metastases are frequently missed and the false negative scan rate is probably quite high. Lung scanning still has its main place in investigating pulmonary embolic disease. Ventilation studies using Xenon 133 are useful, particularly combined with perfusion studies. The various radiopharmaceuticals for use in bone scanning are reviewed. The appearance of technetium labelled phosphate compounds will probably allow much wider use of total skeletal scanning. Research into tumour localizing agents continues, the most recent and interesting being Gallium citrate and labelled bleomycin. Neither agent is predictable however although Gallium may have a place in Hodgkins disease and bronchogenic neoplasm and both may have a place in the detection of cerebral tumours. ImagesFig. 1Fig. 2Fig. 3p452-bFig. 3bFig. 4Fig. 5Fig. 5bFig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 12c & 12dFig. 13Fig. 13 b,c,dFig. 14Fig. 14bFig. 15Fig. 15bFig. 16Fig. 17Fig. 18 PMID:4602127

TGFβ-Id1 Signaling Opposes Twist1 and Promotes Metastatic Colonization Via a Mesenchymal-to-Epithelial Transition

PubMed Central

Stankic, Marko; Pavlovic, Svetlana; Chin, Yvette; Brogi, Edi; Padua, David; Norton, Larry; Massague, Joan; Benezra, Robert

2014-01-01

SUMMARY ID genes are required for breast cancer colonization of the lungs, but the mechanism remains poorly understood. Here, we show that Id1 expression induces a stem-like phenotype in breast cancer cells, while retaining epithelial properties, contrary to the notion that cancer stem-like properties are inextricably linked to the mesenchymal state. During metastatic colonization, Id1 induces a mesenchymal-to-epithelial transition (MET), specifically in cells whose mesenchymal state is dependent on the Id1 target protein Twist1 but not at the primary site, where this state is controlled by the zinc-finger protein Snail1. Knockdown of Id expression in metastasizing cells prevents MET and dramatically reduces lung colonization. Furthermore, Id1 is induced by TGFβ only in cells that have first undergone EMT, demonstrating that EMT is a pre-requisite for subsequent Id1-induced MET during lung colonization. Collectively, these studies underscore the importance of Id-mediated phenotypic switching during distinct stages of breast cancer metastasis. PMID:24332369

[The value of alpha-methylacyl-CoA racemase expression in the progression of colonic carcinoma].

PubMed

López-Valdivia, Cecilia M; González-Matea, Manuel; Mayordomo, Empar; Hervás, David; Ramos, David

Alpha-methylacyl-CoA racemase (AMACR) expression has been demonstrated in several normal tissues and in diverse types of carcinoma. Our aim was to analyze the immunohistochemical expression of AMACR in the sequence-progression of colonic cancer. We studied 237 cases, including samples of normal mucosa of the colon, adenomas with different degrees of dysplasia, colonic carcinomas, lymph nodes and liver metastases of colonic carcinomas. A scale of intensity and percentage of expression was used to analyze the AMACR immunohistochemical profile. The expression was nearly absent in samples of normal mucosa, increased in both adenomas and carcinomas, decreased in lymph node metastases but was significantly increased in liver metastases. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

PubMed

Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

2004-01-01

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy.

PubMed

Kinuya, Seigo; Yokoyama, Kunihiko; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa

2004-07-01

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.

Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

PubMed

Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

2016-01-01

The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

Genomewide association study of liver abscess in beef cattle.

PubMed

Keele, J W; Kuehn, L A; McDaneld, T G; Tait, R G; Jones, S A; Keel, B N; Snelling, W M

2016-02-01

Fourteen percent of U.S. cattle slaughtered in 2011 had liver abscesses, resulting in reduced carcass weight, quality, and value. Liver abscesses can result from a common bacterial cause, , which inhabits rumen lesions caused by acidosis and subsequently escapes into the blood stream, is filtered by the liver, and causes abscesses in the liver. Our aim was to identify SNP associated with liver abscesses in beef cattle. We used lung samples as a DNA source because they have low economic value, they have abundant DNA, and we had unrestricted access to sample them. We collected 2,304 lung samples from a beef processing plant: 1,152 from animals with liver abscess and 1,152 from animals without liver abscess. Lung tissue from pairs of animals, 1 with abscesses and another without, were collected from near one another on the viscera table to ensure that pairs of phenotypically extreme animals came from the same lot. Within each phenotype (abscess or no abscess), cattle were pooled by slaughter sequence into 12 pools of 96 cattle for each phenotype for a total of 24 pools. The pools were constructed by equal volume of frozen lung tissue from each animal. The DNA needed to allelotype each pool was then extracted from pooled lung tissue and the BovineHD Bead Array (777,962 SNP) was run on all 24 pools. Total intensity (TI), an indicator of copy number variants, was the sum of intensities from red and green dyes. Pooling allele frequency (PAF) was red dye intensity divided TI. Total intensity and PAF were weighted by the inverse of their respective genomic covariance matrices computed over all SNP across the genome. A false discovery rate ≤ 5% was achieved for 15 SNP for PAF and 20 SNP for TI. Genes within 50 kbp from significant SNP were in diverse pathways including maintenance of pH homeostasis in the gastrointestinal tract, maintain immune defenses in the liver, migration of leukocytes from the blood into infected tissues, transport of glutamine into the kidney in

Structural and quantitative expression analyses of HERV gene family in human tissues.

PubMed

Ahn, Kung; Kim, Heui-Soo

2009-08-31

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

PubMed Central

2010-01-01

Background Liver × receptor α (LXRα) and β (LXRβ) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumor necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases. PMID:20175894

STUDIES ON THE METABOLISM OF 6-NITROCHRYSENE AND THE FORMATION OF DNA ADDUCTS IN THE LIVER, LUNG AND BLADDER OF A/J MICE

EPA Science Inventory

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Studies On The Metabolism of 6-Nitrochrysene and The Formation of DNA Adducts in the Liver, Lung and Bladder ofAJJ Mice
Moses McDaniel*, Linda Adamst, Joycelyn Allisont, Michael George"l", Dhimant Desai+, 5hantu Amin+, Guy Lambertt, William Padgettt, Stephen Nesnowt and...

Effect of different concentrations of hypertonic saline at different times on protoscoleces of hydatid cyst isolated from liver and lung.

PubMed

Tappeh, Khosrow Hazreti; Einshaei, Ali; Mahmudloo, Rahim; Mohammadzadeh, Habib; Tahermaram, Mansoor; Mousavi, Seyed Javad

2011-01-01

Most surgeons inject scoloidal materials into the cyst before or after its removal, since any contamination to normal sites will cause re-growth of the same cyst. The aim of this study was to determine the lethal effect of hypertonic saline at different doses and different times on protoscolexes of lung and liver. The livers and lungs of killed animals with hydatid cyst disease were gathered from Urmia Industrial Abattoirs. They were transferred to the university parasitological lab immediately. The hydatid cyst fluid was aspirated with a 10 mm syringe and poured into a 15 cc tubes. The movement of protoscoleces and staining with 0.1% eosin was the test to determine viability of protoscoleces. Those with color absorption were those which were not viable. Different concentrations of hypertonic saline were given at different time. The results showed that in 20% of hypertonic saline in the 4th minute, 80% of protoscoleces were alive while in the 5th minute 50% were alive, in the 7th minute 20% and 8th minute 5%, 9th minute all of them were dead. In the 10% concentration, at up to 9 minutes 50% were alive, in the 18th minute 20% and in 30 minutes 10% of protoscoleces were alive. In the 5% concentration at up to 10 minutes 90% were alive while in the 22nd minute 80% and in 30 minutes 70% of protoscoleces were alive. When we inject 20% hypertonic saline into the cyst cavity there is aprobability that the cyst contaminates the bile duct and liver through the small hole we made. This material may cause widespread necrosis of the liver. We should use 10% hypertonic saline minimally for 45 minute before surgery and after cyst removal, since the hypertonic saline itself may cause injury to the biliary system.

Economic burden of cancer among patients with surgical resections of the lung, rectum, liver and uterus: results from a US hospital database claims analysis.

PubMed

Kalsekar, Iftekhar; Hsiao, Chia-Wen; Cheng, Hang; Yadalam, Sashi; Chen, Brian Po-Han; Goldstein, Laura; Yoo, Andrew

2017-12-01

To determine hospital resource utilization, associated costs and the risk of complications during hospitalization for four types of surgical resections and to estimate the incremental burden among patients with cancer compared to those without cancer. Patients (≥18 years old) were identified from the Premier Research Database of US hospitals if they had any of the following types of elective surgical resections between 1/2008 and 12/2014: lung lobectomy, lower anterior resection of the rectum (LAR), liver wedge resection, or total hysterectomy. Cancer status was determined based on ICD-9-CM diagnosis codes. Operating room time (ORT), length of stay (LOS), and total hospital costs, as well as frequency of bleeding and infections during hospitalization were evaluated. The impact of cancer status on outcomes (from a hospital perspective) was evaluated using multivariable generalized estimating equation models; analyses were conducted separately for each resection type. Among the identified patients who underwent surgical resection, 23 858 (87.9% with cancer) underwent lung lobectomy, 13 522 (63.8% with cancer) underwent LAR, 2916 (30.0% with cancer) underwent liver wedge resection and 225 075 (11.3% with cancer) underwent total hysterectomy. After adjusting for patient, procedural, and hospital characteristics, mean ORT, LOS, and hospital cost were statistically higher by 3.2%, 8.2%, and 9.2%, respectively for patients with cancer vs. no cancer who underwent lung lobectomy; statistically higher by 6.9%, 9.4%, and 9.6%, respectively for patients with cancer vs. no cancer who underwent LAR; statistically higher by 4.9%, 14.8%, and 15.7%, respectively for patients with cancer vs. no cancer who underwent liver wedge resection; and statistically higher by 16.0%, 27.4%, and 31.3%, respectively for patients with cancer vs. no cancer who underwent total hysterectomy. Among patients who underwent each type of resection, risks for bleeding and infection were generally higher

Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

PubMed Central

Elshenawy, Osama H.; Shoieb, Sherif M.; Mohamed, Anwar; El-Kadi, Ayman O.S.

2017-01-01

Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. PMID:28230738

Study of endothelin-1 and vascular endothelial growth factor in patients with cancer colon.

PubMed

Abdel-Gawad, Iman A; Hassanein, Hala M R; Bahgat, Nahla A; Abdel Sattar, Mona A; El-Sissy, Azza H; Altaweel, Maha A; Helal, Amany M

2008-09-01

The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some prognostic factors of cancer colon were also investigated. The study included 48 patients with cancer colon and 20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range from 18 to 71 years (mean = 47 +/- 1.8). Both serum and plasma samples were obtained from patients and controls. Six percent of patients had grade 1 tumors, 77 % had grade 2 and 17 % had grade 3 disease. As regard to the stage, 52 % of patients were stage II, 35.5 % were stage III, while 12.5 % were stage IV. Liver metastasis was present in 12.5 %, while 35 % showed lymph node metastasis. The VEGF, endothelin-1, CA19.9 and CEA were significantly higher in the cancer colon patients than in control groups (p-value < 0.001,0.006, < 0.001 and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher levels in advanced stages of the disease (p value < 0.001) and in presence of liver metastasis (p value <0.00l and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value = 0.032). In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic, non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically significant for both markers (p < 0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77 and p-value < 0.0001). Serum VEGF and CA19.9 showed good sensitivities which were not different (97.9 % and 87.5 % ,respectively), while there was no significant difference between VEGF, CA19.9 and CEA with respect to specificities (100 %, 90 % and 100 % respectively). Both endothelin-1 and VEGF may be used for early detection of liver metastasis in cancer colon and VEGF

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

PubMed

Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri

2007-08-15

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.

[The specificity between "fei and dachang" in the lung injury of rats with ulcerative colitis].

PubMed

Zhu, Li; Wang, Xin-yue; Yang, Xue; Jing, Shan; Zhou, Bo; Huang, Xiu-xia; Jia, Xu

2013-03-01

To observe the features of bronchopulmonary lesions in ulcerative colitis (UC) rats and the specificity with Fei and Dachang, thus providing reliance for the theory of "intestinal diseases involved Fei". The UC rat model was duplicated by using rabbit intestine mucosa tissue allergenic model and TNBS-ethanol model. A normal rat group was set up as the control. The pulmonary functions [including inspiratory resistance (Ri), expiratory resistance (Re), forced vital capacity (FVC); FEV. 2/FVC, maximal voluntary ventilation (MVV), forced expiratory flow rate (FEF25% - 75%)], and indicators of liver and kidney functions [serum alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] were detected in the two groups. The pathological changes of colon, lung, liver, and kidney were observed in the two groups. Rats in the model group in both acute and chronic stages had weight loss, mucus and loose stool. Partial rats had such symptoms as dyspnea, shortness of breath, and wheezing. Compared with the normal group, the MW, FVC, FEV0.2 and FEF25% -75% in the acute stage; Ri, Re, MVV, FVC, and FEF25% - 75% in the chronic stage all significantly decreased (P <0.05, P <0.01), and FEV0.2/FVC significantly increased in the model group (P <0.05). The pathological results showed interstitial pneumonia and pulmonary interstitial fibrosis in the model group. But the indicators of liver and kidney functions were all in the normal range. No obvious pathological change was seen in the renal and liver tissues in the two groups. UC could specifically induce bronchopulmonary lesions. Lung injury was one of UC's intestinal manifestations. The theory of "Fei and Dachang being interior-exteriorly correlated" was demonstrated from the theory of "intestinal diseases involved Fei".

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

PubMed

Alanin, Mikkel Christian; Aanaes, Kasper; Høiby, Niels; Pressler, Tania; Skov, Marianne; Nielsen, Kim Gjerum; Johansen, Helle Krogh; von Buchwald, Christian

2017-03-01

Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS. Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function. © 2016 ARS-AAOA, LLC.

Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases.

PubMed

van Haaften, Timothy; Thébaud, Bernard

2006-04-01

Bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF) are two common serious chronic respiratory disorders without specific treatments affecting children. BPD is characterized by an arrest in alveolar growth in premature infants requiring respiratory support. CF is the most common fatal inherited genetic disorder characterized by abnormally thick mucus secretions, recurrent infection and ultimately lung destruction. One commonality between these two diseases is the promise of utilizing stem cells therapeutically. Indeed, the use of exogenous cells to supplement the natural repair mechanisms or the possibility of genetic manipulation in vitro before administration are appealing therapeutic options for these diseases. Increasing attention has been focused on the use of adult bone marrow-derived stem cells (BMSC) to regenerate damaged organs such as the heart, the brain, and the liver. However, due to the lung's complexity as well as the low rate of cellular turnover within the lung, progress has been slower in this area compared with the skin or liver. Initial work suggests that BMSC can engraft and differentiate into a variety of lung cells, but these findings have been challenged recently. This article critically reviews the current advances on the therapeutic use of stem cells for lung regeneration.

Serum Phospholipid Fatty Acid Composition in Cystic Fibrosis Patients with and without Liver Cirrhosis.

PubMed

Drzymała-Czyż, Sławomira; Szczepanik, Mariusz; Krzyżanowska, Patrycja; Duś-Żuchowska, Monika; Pogorzelski, Andrzej; Sapiejka, Ewa; Juszczak, Paweł; Lisowska, Aleksandra; Koletzko, Berthold; Walkowiak, Jarosław

2017-01-01

Cystic fibrosis (CF) liver disease is the third most frequent cause of death in CF patients. Although it alters fatty acid (FA) metabolism, data concerning the profile of FA in CF patients with liver cirrhosis is lacking. This study aimed to assess the FA composition of serum phospholipids in CF patients with and without liver cirrhosis. The study comprised 25 CF patients with liver cirrhosis and 25 without it. We assessed Z-scores for body height and weight, lung function, exocrine pancreatic sufficiency and colonization with Pseudomonas aeruginosa. FAs' profile of serum glycerophospholipids was quantified by gas chromatography mass spectrometry. In CF patients with liver cirrhosis, the levels of C16:0 were higher and the amounts of C20:2n-6, C20:3n-6, C20:4n-6, and all the n-3 polyunsaturated FAs (PUFAs) (C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3) were lower than those in CF subjects without liver cirrhosis. The n-6/n-3, C20:4n-6/C18:2n-6, total n-6/C18:2n-6, C20:5n-3/C18:3n-3 and total n-3/C18:3n-3 ratios did not differ between the 2 groups. Liver cirrhosis may associate with profound abnormalities in the composition of serum glycerophospholipids FAs in CF patients. None of the analyzed clinical factors could explain the greater prevalence of low levels of PUFAs in this CF subgroup. © 2017 S. Karger AG, Basel.

Colonization-Induced Host-Gut Microbial Metabolic Interaction

PubMed Central

Claus, Sandrine P.; Ellero, Sandrine L.; Berger, Bernard; Krause, Lutz; Bruttin, Anne; Molina, Jérôme; Paris, Alain; Want, Elizabeth J.; de Waziers, Isabelle; Cloarec, Olivier; Richards, Selena E.; Wang, Yulan; Dumas, Marc-Emmanuel; Ross, Alastair; Rezzi, Serge; Kochhar, Sunil; Van Bladeren, Peter; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.

2011-01-01

The gut microbiota enhances the host’s metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care. PMID:21363910

Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery

ClinicalTrials.gov

2014-05-07

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Recurrence pattern depends on the location of colon cancer in the patients with synchronous colorectal liver metastasis.

PubMed

Lee, Huisong; Choi, Dong Wook; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong; Heo, Jin Seok; Choi, Seong Ho; Jung, Kyung Uk; Chun, Ho-Kyung

2014-05-01

The veins from the lower rectum drain into the systemic venous system, while those from other parts of the colon drain into the portal venous system. The aim of this study was to investigate recurrence pattern and survival according to the anatomical differences in patients with colorectal liver metastases (CRLM). From October 1994 to December 2009, synchronous CRLM patients who underwent surgery were identified from our prospectively collected database. The patients were excluded if there had been extrahepatic metastases. The patients were divided into two groups according to the location of the primary colorectal cancer: lower rectal cancer (group 1) and upper rectal or colon cancer (group 2). The recurrence patterns and survival were investigated. A total of 316 patients were included: 53 patients in group 1 and 263 patients in group 2. After a median follow-up of 37 months, the extrahepatic recurrence curve of group 1 was superior to that of group 2 (P < 0.001), although there was no difference between the hepatic recurrence curves (P = 0.93). The disease-free and overall survival curves of group 1 were inferior to those of group 2 (P = 0.004) (P < 0.001). Lower rectal cancer was a significant risk factor for extrahepatic recurrence in Cox proportional hazard model analysis (hazard ratio = 1.7, P = 0.04). The extrahepatic recurrence rate is high in lower rectal cancer patients after surgical treatment for synchronous CRLM.

Long-Term Colonization of the Cystic Fibrosis Lung by Burkholderia cepacia Complex Bacteria: Epidemiology, Clonal Variation, and Genome-Wide Expression Alterations

PubMed Central

Coutinho, Carla P.; dos Santos, Sandra C.; Madeira, Andreia; Mira, Nuno P.; Moreira, Ana S.; Sá-Correia, Isabel

2011-01-01

Long-term respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) patients generally lead to a more rapid decline in lung function and, in some cases, to a fatal necrotizing pneumonia known as the “cepacia syndrome.” Bcc bacteria are ubiquitous in the environment and are recognized as serious opportunistic pathogens that are virtually impossible to eradicate from the CF lung, posing a serious clinical threat. The epidemiological survey of Bcc bacteria involved in respiratory infections at the major Portuguese CF Treatment Center at Santa Maria Hospital, in Lisbon, has been carried out by our research group for the past 16 years, covering over 500 clinical isolates where B. cepacia and B. cenocepacia are the predominant species, with B. stabilis, B. contaminans, B. dolosa, and B. multivorans also represented. The systematic and longitudinal study of this CF population during such an extended period of time represents a unique case–study, comprehending 41 Bcc-infected patients (29 pediatric and 12 adult) of whom around 70% have been persistently colonized between 7 months and 9 years. During chronic infection, the CF airways represent an evolving ecosystem, with multiple phenotypic variants emerging from the clonal population and becoming established in the patients’ airways as the result of genetic adaptation. Understanding the evolutionary mechanisms involved is crucial for an improved therapeutic outcome of chronic infections in CF. This review focuses on our contribution to the understanding of these adaptive mechanisms based on extensive phenotypic, genotypic, and genome-wide expression approaches of selected Bcc clonal variants obtained during long-term colonization of the CF airways. PMID:22919578

Long-term colonization of the cystic fibrosis lung by Burkholderia cepacia complex bacteria: epidemiology, clonal variation, and genome-wide expression alterations.

PubMed

Coutinho, Carla P; Dos Santos, Sandra C; Madeira, Andreia; Mira, Nuno P; Moreira, Ana S; Sá-Correia, Isabel

2011-01-01

Long-term respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) patients generally lead to a more rapid decline in lung function and, in some cases, to a fatal necrotizing pneumonia known as the "cepacia syndrome." Bcc bacteria are ubiquitous in the environment and are recognized as serious opportunistic pathogens that are virtually impossible to eradicate from the CF lung, posing a serious clinical threat. The epidemiological survey of Bcc bacteria involved in respiratory infections at the major Portuguese CF Treatment Center at Santa Maria Hospital, in Lisbon, has been carried out by our research group for the past 16 years, covering over 500 clinical isolates where B. cepacia and B. cenocepacia are the predominant species, with B. stabilis, B. contaminans, B. dolosa, and B. multivorans also represented. The systematic and longitudinal study of this CF population during such an extended period of time represents a unique case-study, comprehending 41 Bcc-infected patients (29 pediatric and 12 adult) of whom around 70% have been persistently colonized between 7 months and 9 years. During chronic infection, the CF airways represent an evolving ecosystem, with multiple phenotypic variants emerging from the clonal population and becoming established in the patients' airways as the result of genetic adaptation. Understanding the evolutionary mechanisms involved is crucial for an improved therapeutic outcome of chronic infections in CF. This review focuses on our contribution to the understanding of these adaptive mechanisms based on extensive phenotypic, genotypic, and genome-wide expression approaches of selected Bcc clonal variants obtained during long-term colonization of the CF airways.

Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats

PubMed Central

2012-01-01

Background Macrophages in other organs (e.g. kidneys, lungs, and spleen, et. al) have rarely been reported in the development of liver fibrosis. Therefore, it is important to investigate macrophage activation in the main organs in liver fibrosis. We investigated the potential antifibrogenic effects of paeoniflorin (PF) in a dimethylnitrosamine (DMN)-induced rat model with special focus on inhibiting macrophage activation in the main organs. Methods Rat hepatic fibrosis was induced by treatment with DMN three times weekly over a 4-week period. DMN rats were treated with water, PF, or gadolinium chloride (GdCl3) from the beginning of the 3rd week. The expression of CD68, marker of macrophage, was investigated using immunohistochemical, real-time PCR, and western blot analysis. Results Hepatic hydroxyproline content markedly decreased and histopathology improved in the DMN-PF rats. Expression of desmin and collagen 1 decreased notably in DMN-PF liver. CD68 expression in the liver, spleen and kidney increased markedly after 2 weeks but decreased in DMN-water rats. PF and GdCl3 decreased CD68 expression in the liver and spleen and there was no effect on kidney. CD68 expression in the lung increased gradually during the course of DMN-induced liver fibrosis, and PF inhibited CD68 expression in the lung significantly while GdCl3 increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl3 in the liver, as revealed by real-time PCR analysis. However, GdCl3 could not decrease TNF-α level in the serum by enzyme linked immunosorbent assay (ELISA). Conclusions Macrophage activation was disrupted in the liver, spleen, lung and kidney during development of DMN-induced liver fibrosis. PF administration attenuated DMN-induced liver fibrosis at least in part by regulating macrophage disruption in the main organs. PMID:23237422

Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

PubMed

Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

2013-12-01

Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

Metastatic spread pattern after curative colorectal cancer surgery. A retrospective, longitudinal analysis.

PubMed

Augestad, K M; Bakaki, P M; Rose, J; Crawshaw, B P; Lindsetmo, R O; Dørum, L M; Koroukian, S M; Delaney, C P

2015-10-01

The most common sites of colorectal cancer (CRC) recurrence are the local tissues, liver or lungs. The objective was to identify risk factors associated with the primary CRC tumor and cancer recurrence in these anatomical sites. Retrospective, longitudinal analyses of data on CRC survivors. Multivariable Cox regression analysis was performed to examine the association between possible cofounders with recurrence to various anatomical sites. Data for 10,398CRC survivors (tumor location right colon=3870, left colon=2898, high rectum=2569, low rectum=1061) were analyzed; follow up time was up to five years. Mean age at curative surgery was 71.5 (SD 11.8) years, 20.2% received radio-chemotherapy, stage T3 (64.4%) and N0 (65.1%) were most common. Overall 1632 (15.7%) had cancer recurrence (Isolated liver n=412, 3,8%;  isolated lung n=252, 2,4%; isolated local n=223, 2.1%). Risk factors associated with recurrent CRC were identified, i.e. isolated liver metastases (male: Adjusted Hazard Ratio (AHR) 1,45; colon left: AHR 1,63; N2 disease: AHR 3,35; T2 disease: AHR 2,82), isolated lung metastases (colon left: AHR 1,53; rectum high: AHR 2,48; rectum low: AHR 2,65; N2 disease 3,76), and local recurrence (glands examined<12: AHR 1,51; CRM <3mm: AHR 1,60; rectum high: AHR 2,15; N2 disease: AHR 2,58) (all p values <0001). Our study finds that the site of the primary CRC tumor is associated with location of subsequent metastasis. Left sided colon cancers have increased risk of metastatic spread to the liver, whereas rectal cancers have increased risk of local recurrence and metastatic spread to the lungs. These results, in combination with other risk factors for CRC recurrence, should be taken into consideration when designing risk adapted post-treatment CRC surveillance programs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.

PubMed

Guan, Pei-Pei; Yu, Xin; Guo, Jian-Jun; Wang, Yue; Wang, Tao; Li, Jia-Yi; Konstantopoulos, Konstantinos; Wang, Zhan-You; Wang, Pu

2015-04-20

Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.

Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.

PubMed

Choi, Kevin J; Cheng, Tracy Z; Honeybrook, Adam L; Gray, Alice L; Snyder, Laurie D; Palmer, Scott M; Abi Hachem, Ralph; Jang, David W

2018-03-01

Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes. © 2017 ARS-AAOA, LLC.

Lung Cancer Rates by State

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Rates by State for Other Kinds of Cancer All Cancers Combined Breast Cervical Colorectal (Colon) HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English (US) ...

Autologous Bone Marrow Stromal Cells Genetically Engineered to Secrete an IGF-I Receptor Decoy Prevent the Growth of Liver Metastases

PubMed Central

Wang, Ni; Fallavollita, Lucia; Nguyen, Long; Burnier, Julia; Rafei, Moutih; Galipeau, Jacques; Yakar, Shoshana; Brodt, Pnina

2009-01-01

Liver metastases respond poorly to current therapy and remain a frequent cause of cancer-related mortality. We reported previously that tumor cells expressing a soluble form of the insulin-like growth factor-I receptor (sIGFIR) lost the ability to metastasize to the liver. Here, we sought to develop a novel therapeutic approach for prevention of hepatic metastasis based on sustained in vivo delivery of the soluble receptor by genetically engineered autologous bone marrow stromal cells. We found that when implanted into mice, these cells secreted high plasma levels of sIGFIR and inhibited experimental hepatic metastases of colon and lung carcinoma cells. In hepatic micrometastases, a reduction in intralesional angiogenesis and increased tumor cell apoptosis were observed. The results show that the soluble receptor acted as a decoy to abort insulin-like growth factor-I receptor (IGF-IR) functions during the early stages of metastasis and identify sustained sIGFIR delivery by cell-based vehicles as a potential approach for prevention of hepatic metastasis. PMID:19367255

Absorption and distribution of lycopene in rat colon.

PubMed

Oshima, S; Inakuma, T; Narisawa, T

1999-01-01

Colonic absorption and distribution of lycopene, which inhibited rat colon carcinogenesis in our previous studies, were investigated in Sprague-Dawley rats. Three groups of six rats each with or without a single-barreled colostomy at the mid colon were given a single intragastric or intracolonic dose of 0.2 mL of corn oil containing 12 mg of lycopene. Twenty-four hours later, all rats were sacrificed and the blood and some tissues were collected. The contents of lycopene in the samples were assayed by HPLC. Lycopene was detected in an appreciable amount in the liver, but only in trace amount in the serum of all rats treated with an intracolonic dose of lycopene and in rats with an intragastric dose. After an intragastric lycopene treatment, lycopene was detected in the mucosa of the proximal colon and of the distal colon of the colostomized rats, whose distal colon had been excluded from the fecal stream. A large amount of lycopene was recovered in the feces. None was detected in any sample from the control rats treated with an intragastric or intracolonic dose of plain corn oil. The results suggest that lycopene is absorbed from the colon and also from the small intestine. It might be concluded that both ways of absorption contribute to a comparative amount of lycopene accumulation in the colon mucosa after ingestion of this carotenoid.

[Submucosal bacterial abscesses of the ascending colon and liver associated with portal and superior mesenteric vein thrombosis due to Enterococcus faecalis infection: a case report].

PubMed

Norimura, Daisuke; Takeshima, Fuminao; Satou, Yoshiaki; Nakagoe, Tohru; Ohnita, Ken; Isomoto, Hajime; Nakao, Kazuhiko

2014-06-01

A 72-year-old woman with diabetes mellitus was admitted with fever and general fatigue. Blood biochemistry showed elevated hepatic and biliary enzyme levels, abdominal computed tomography showed multiple liver abscesses with portal and superior mesenteric vein thrombosis, and total colonoscopy revealed a submucosal bacterial abscess in the ascending colon. The abscesses were determined to be associated with Enterococcus faecalis infection. The patient was treated conservatively with antibiotics (meropenem) and anticoagulants (warfarin), which led to a gradual amelioration of symptoms and resolution of thrombosis.

Radioimmunoguided surgery in primary colon cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieroda, C.A.; Mojzisik, C.; Sardi, A.

1990-01-01

Radioimmunoguided surgery (RIGS), the intraoperative use of a hand-held gamma detecting probe (GDP) to identify tissue containing radiolabeled monoclonal antibody (MAb), was performed upon 30 patients with primary colon carcinoma. Each patient received an intravenous injection of MAb B72.3 (1.0 to 0.25 mg) radiolabeled with {sup 125}I (5.0 to 1.0 mCi) 8 to 34 days before exploration. The GDP was used to measure radioactivity in colon tissue, tumor bed, nodal drainage areas, and areas of suspected metastases. Antibody localized to histologically documented tumor in 23 of 30 patients (77%). Tumor margins were more clearly defined in 20 of 30 patientsmore » (67%). GDP counts led to major alterations in surgical resection in five patients (17%) and changes in adjuvant therapy in four (14%). GDP counts identified occult liver metastases in two patients (7%) and correctly indicated the benign nature of liver masses in three (10%). In four patients (13%), occult nodal metastases were identified. RIGS can precisely delineate tumor margins, define the extent of nodal involvement, and localize occult tumor, providing a method of immediate intraoperative staging that may lessen recurrences and produce higher survival rates.« less

Alcohol and liver disease in Europe--Simple measures have the potential to prevent tens of thousands of premature deaths.

PubMed

Sheron, Nick

2016-04-01

In the World Health Organisation European Region, more than 2,370,000 years of life are lost from liver disease before the age of 50; more than lung cancer, trachea, bronchus, oesophageal, stomach, colon, rectum and pancreatic cancer combined. Between 60-80% of these deaths are alcohol related, a disease for which no pharmaceutical therapy has yet been shown to improve long-term survival. The toxicity of alcohol is dose related at an individual level, and is dose related at a population level; overall liver mortality is largely determined by population alcohol consumption. Trends in alcohol consumption correlate closely with trends in overall liver mortality, with 3-5-fold decreases or increases in liver mortality in different European countries over the last few decades. The evidence base for alcohol control measures aimed at reducing population alcohol consumption has been subjected to rigorous evaluation; most recently by the Organisation for Economic Co-Operation and Development (OECD). Effective alcohol policy measures reduce alcohol mortality, including mortality from liver disease. The most effective and cost effective measures have been summarised by the OECD and the World Health Organisation: regular incremental above inflation tax increases, a minimum price for alcohol, effective protection of children from alcohol marketing and low level interventions from clinicians. Simple, cheap and effective changes to alcohol policy by European Institutions and member states have the potential to dramatically reduce liver mortality in Europe. Copyright © 2016. Published by Elsevier B.V.

Relationship between postoperative lung atelectasis and position of the endotracheal tube in pediatric living-donor liver transplantation.

PubMed

Lee, H-Y; Lu, C-H; Lu, H-F; Chen, C-L; Wang, C-H; Cheng, K-W; Wu, S-C; Jawan, B; Huang, C-J

2012-05-01

The aims of current study were: 1) to evaluate the incidence of lung atelectasis; and 2) to investigate whether or not the position of the endotracheal (ET) tube is associated with this complication. The medical records and chest roentgenograms of 183 pediatric patients who underwent living-donor liver transplantation were retrospectively reviewed and analyzed. Patients without atelectasis were grouped in group I (GI) and those with atelectasis in group II (GII). The patients' characteristics and ET tube level between groups were compared with unpaired Student's t test. Multiple binary logistic regressions were also performed to identify the important risk factors associated with lung atelectasis. Right upper lung (RUL) atelectsis could be found in ET tube at any level from T1 to T5, with incidence rates of 12.7%, 15.2%, 26.3%, 6.7%, and 100% for T1, T2, T3, T4, and T5, respectively. The incidence of atelectasis is 16.6%, and all of the atelectasis occurred in the RUL. No significant difference between groups was observed in the patients' characteristics, except for the amount of preoperative ascites. The likelihood of this risk factor could not be confirmed by multivariate binary logistic regression analysis. The incidence of lung atelectasis in our study was 16.6%, which all occurred in the RUL. No predictive risk factor from the patients' characteristics could be found, and no correlation between the level of the ET tube and the occurrence of RUL atelectasis could be observed. Copyright © 2012 Elsevier Inc. All rights reserved.

Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study.

PubMed

Liang, Yi-Hsin; Shao, Yu-Yun; Chen, Ho-Min; Cheng, Ann-Lii; Lai, Mei-Shu; Yeh, Kun-Huei

2017-12-01

Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001). Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

MO-G-17A-06: Kernel Based Dosimetry for 90Y Microsphere Liver Therapy Using 90Y Bremsstrahlung SPECT/CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikell, J; Siman, W; Kappadath, S

2014-06-15

Purpose: 90Y microsphere therapy in liver presents a situation where beta transport is dominant and the tissue is relatively homogenous. We compare voxel-based absorbed doses from a 90Y kernel to Monte Carlo (MC) using quantitative 90Y bremsstrahlung SPECT/CT as source distribution. Methods: Liver, normal liver, and tumors were delineated by an interventional radiologist using contrast-enhanced CT registered with 90Y SPECT/CT scans for 14 therapies. Right lung was segmented via region growing. The kernel was generated with 1.04 g/cc soft tissue for 4.8 mm voxel matching the SPECT. MC simulation materials included air, lung, soft tissue, and bone with varying densities.more » We report percent difference between kernel and MC (%Δ(K,MC)) for mean absorbed dose, D70, and V20Gy in total liver, normal liver, tumors, and right lung. We also report %Δ(K,MC) for heterogeneity metrics: coefficient of variation (COV) and D10/D90. The impact of spatial resolution (0, 10, 20 mm FWHM) and lung shunt fraction (LSF) (1,5,10,20%) on the accuracy of MC and kernel doses near the liver-lung interface was modeled in 1D. We report the distance from the interface where errors become <10% of unblurred MC as d10(side of interface, dose calculation, FWHM blurring, LSF). Results: The %Δ(K,MC) for mean, D70, and V20Gy in tumor and liver was <7% while right lung differences varied from 60–90%. The %Δ(K,MC) for COV was <4.8% for tumor and liver and <54% for the right lung. The %Δ(K,MC) for D10/D90 was <5% for 22/23 tumors. d10(liver,MC,10,1–20) awere <9mm and d10(liver,MC,20,1–20) awere <15mm; both agreed within 3mm to the kernel. d10(lung,MC,10,20), d10(lung,MC,10,1), d10(lung,MC,20,20), and d10(lung,MC,20,1) awere 6, 25, 15, and 34mm, respectively. Kernel calculations on blurred distributions in lung had errors > 10%. Conclusions: Liver and tumor voxel doses with 90Y kernel and MC agree within 7%. Large differences exist between the two methods in right lung. Research reported

Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer.

PubMed

Allard, W J; Neaman, I E; Elting, J J; Barnett, T R; Yoshimura, H; Fritsche, H A; Yeung, K K

1994-03-01

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the

[A Long-Term Disease-Free Survival Case of Synchronous Pulmonary and Liver Metastasis of Rectal Cancer with Systemic Chemotherapy and Radiofrequency Ablation Therapy for Liver Metastasis].

PubMed

Enomoto, Masaya; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Matsudo, Takaaki; Shigoka, Masatoshi; Enomoto, Masanobu; Ishizaki, Tetsuo; Tsuchida, Akihiko

2017-11-01

A 55-year-old woman underwent laparoscopic anterior resection and D2 lymph node dissection for recto-sigmoid colon cancer in November 2014, which was diagnosed as T3N1M1(H3, PUL2), stage IV , for the purpose of preserving the ileus. FOLFOX therapy with panitumumab(Pmab)was started in January 2015.A t the end of 11 courses, pulmonary metastasis changed to CR, and liver metastasis was down-graded to H2 on the CT.Because of the risk of hepatic dysfunction with advanced fatty liver due to chemotherapy and extrahepatic lesions, we chose radiofrequency ablation(RFA)therapy for liver metastasis.Pmab combined FOLFIRI therapy was administered, and maintenance therapy was initiated.This patient is alive 2 years and 7 months after surgery and 10 months after RFA without relapse.It is suggested that RFA therapy for liver metastasis of colon cancer with pulmonary metastasis combined with chemotherapy could be an effective treatment strategy.

Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence.

PubMed

Alaiyan, Bilal; Ilyayev, Nadia; Stojadinovic, Alexander; Izadjoo, Mina; Roistacher, Marina; Pavlov, Vera; Tzivin, Victoria; Halle, David; Pan, Honguang; Trink, Barry; Gure, Ali O; Nissan, Aviram

2013-04-17

The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the

Amebic lung abscess with coexisting lung adenocarcinoma: a unusual case of amebiasis.

PubMed

Zhu, Hailong; Min, Xiangyang; Li, Shuai; Feng, Meng; Zhang, Guofeng; Yi, Xianghua

2014-01-01

Amebic lung abscess with concurrent lung cancer, but without either a liver abscess or amebic colitis, is extremely uncommon. Here, we report a 70-year-old man presenting with pulmonary amebiasis and coexisting lung adenocarcinoma. During his first-time hospitalization, the diagnosis of lung amebiasis was confirmed by morphological observation and PCR in formalin-fixed and paraffin-embedded sediments of pleural effusion. Almost four months later, the patient was readmitted to hospital for similar complaints. On readmission, lung adenocarcinoma was diagnosed by liquid-based sputum cytology and thought to be delayed because coexisting amebic lung abscess. This case demonstrated that sediments of pleural effusion may be used for further pathological examination after routine cytology has shown negative results. At the same time, we concluded that lung cancer may easily go undetected in the patients with pulmonary amebiasis and repetitive evaluation by cytology and imaging follow-up are useful to find potential cancer.

Amebic lung abscess with coexisting lung adenocarcinoma: a unusual case of amebiasis

PubMed Central

Zhu, Hailong; Min, Xiangyang; Li, Shuai; Feng, Meng; Zhang, Guofeng; Yi, Xianghua

2014-01-01

Amebic lung abscess with concurrent lung cancer, but without either a liver abscess or amebic colitis, is extremely uncommon. Here, we report a 70-year-old man presenting with pulmonary amebiasis and coexisting lung adenocarcinoma. During his first-time hospitalization, the diagnosis of lung amebiasis was confirmed by morphological observation and PCR in formalin-fixed and paraffin-embedded sediments of pleural effusion. Almost four months later, the patient was readmitted to hospital for similar complaints. On readmission, lung adenocarcinoma was diagnosed by liquid-based sputum cytology and thought to be delayed because coexisting amebic lung abscess. This case demonstrated that sediments of pleural effusion may be used for further pathological examination after routine cytology has shown negative results. At the same time, we concluded that lung cancer may easily go undetected in the patients with pulmonary amebiasis and repetitive evaluation by cytology and imaging follow-up are useful to find potential cancer. PMID:25550881

77 FR 43601 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... of the patent applications. Novel Analogues of the Asthma Drug Fenoterol as Liver and Brain Cancer... as MNF, that inhibit the growth of various types of cancers, including brain, liver, colon, and lung..., represents one of the first potential drugs directed at this target. MNF crosses the blood brain barrier and...

Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

PubMed Central

Richard, Egbe Edmund; Augusta Chinyere, Nsonwu-Anyanwu; Jeremaiah, Offor Sunday; Opara, Usoro Chinyere Adanna; Henrieta, Etukudo Maise; Ifunanya, Egbe Deborah

2016-01-01

Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)}, and serum elements {lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p = 0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p < 0.05). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p < 0.05). Negative correlation was observed between duration of exposure and PEFR (r = −0.416, p = 0.016) in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. PMID:26981118

Sambar, an Indian Dish Prevents the Development of Dimethyl Hydrazine–Induced Colon Cancer: A Preclinical Study

PubMed Central

Prasad, Vutturu Ganga; Reddy, Neetinkumar; Francis, Albi; Nayak, Pawan G.; Kishore, Anoop; Nandakumar, Krishnadas; Rao, Mallikarjuna C.; Shenoy, Rekha

2016-01-01

Background: Colon cancer (CC) is the third commonly diagnosed cancer and the second leading cause of mortality in the US when compared to India where prevalence is less. Possible reason could be the vegetarian diet comprising spices used in curry powders. Researchers believe that 70% of the cases are associated with diet. Spices have inherited a rich tradition for their flavor and medicinal properties. Researchers have been oriented towards spices present in food items for their antitumorigenic properties. Objective: We investigated the effects of sambar as a preventive measure for 1,2-dimethyl hydrazine (DMH)-induced CC in Wistar albino rats. Materials and Methods: The animals were divided into three groups (n = 6) namely control, DMH, and sambar. At the end of the experimental period, the animals were killed using anesthesia and the colons and livers were examined. Results: All the treatment groups exhibited a significant change in the number of aberrant crypt foci (ACF). Sambar group showed a significant change in the colonic GSH when compared to both normal and DMH groups. A significant reduction in the liver GSH was noted in the sambar group. Only sambar group showed a significant change in the liver catalase levels when compared to DMH. There was a significant reduction in the colonic nitrite in the sambar-treated group; 2.94 ± 0.29 when compared to DMH control at 8.09 ± 1.32. On the contrary, a significant rise in the liver nitrite levels was observed in the sambar-treated rats. Conclusion: Sambar may prevent the risk of CC when consumed in dietary proportions. SUMMARY Consumption of sambar significantly reduced aberrant crypt foci in DMH-induced colon cancer modelSambar treatment prevented DMH-induced oxidative changes in the colonic tissue, indicating its antioxidant roleSambar comprises a variety of spices that exhibited both pro- and antioxidant properties in different tissues, leading to its overall beneficial effect in this model. Abbreviations used

Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

NASA Astrophysics Data System (ADS)

Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M. J.

2010-07-01

A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe ( P=0.009) from independent T test.

Kinetics of Ethylene and Ethylene Oxide in Subcellular Fractions of Lungs and Livers of Male B6C3F1 Mice and Male Fischer 344 Rats and of Human Livers

PubMed Central

Csanády, György András; Kessler, Winfried; Klein, Dominik; Pankratz, Helmut; Pütz, Christian; Richter, Nadine; Filser, Johannes Georg

2011-01-01

Ethylene (ET) is metabolized in mammals to the carcinogenic ethylene oxide (EO). Although both gases are of high industrial relevance, only limited data exist on the toxicokinetics of ET in mice and of EO in humans. Metabolism of ET is related to cytochrome P450-dependent mono-oxygenase (CYP) and of EO to epoxide hydrolase (EH) and glutathione S-transferase (GST). Kinetics of ET metabolism to EO and of elimination of EO were investigated in headspace vessels containing incubations of subcellular fractions of mouse, rat, or human liver or of mouse or rat lung. CYP-associated metabolism of ET and GST-related metabolism of EO were found in microsomes and cytosol, respectively, of each species. EH-related metabolism of EO was not detectable in hepatic microsomes of rats and mice but obeyed saturation kinetics in hepatic microsomes of humans. In ET-exposed liver microsomes, metabolism of ET to EO followed Michaelis-Menten-like kinetics. Mean values of Vmax [nmol/(min·mg protein)] and of the apparent Michaelis constant (Km [mmol/l ET in microsomal suspension]) were 0.567 and 0.0093 (mouse), 0.401 and 0.031 (rat), and 0.219 and 0.013 (human). In lung microsomes, Vmax values were 0.073 (mouse) and 0.055 (rat). During ET exposure, the rate of EO production decreased rapidly. By modeling a suicide inhibition mechanism, rate constants for CYP-mediated catalysis and CYP inactivation were estimated. In liver cytosol, mean GST activities to EO expressed as Vmax/Km [μl/(min·mg protein)] were 27.90 (mouse), 5.30 (rat), and 1.14 (human). The parameters are most relevant for reducing uncertainties in the risk assessment of ET and EO. PMID:21785163

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically

Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

PubMed Central

Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

2015-01-01

Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b(+) myeloid cells to the lungs and facilitates B16-F10 melanoma colonization.

PubMed

Souza, Lucas E B; Almeida, Danilo C; Yaochite, Juliana N U; Covas, Dimas T; Fontes, Aparecida M

2016-07-15

The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b(+) myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize "premetastatic niches" in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b(+) myeloid cells and tumor cells. Copyright © 2015 Elsevier Inc. All rights reserved.

By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization

PubMed Central

Guan, Pei-Pei; Yu, Xin; Guo, Jian-Jun; Wang, Yue; Wang, Tao; Li, Jia-Yi; Konstantopoulos, Konstantinos; Wang, Zhan-You; Wang, Pu

2015-01-01

Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis. PMID:25823818

ALDEHYDE DEHYDROGENASES EXPRESSION DURING POSTNATAL DEVELOPMENT: LIVER VS. LUNG

EPA Science Inventory

Aldehydes are highly reactive molecules present in the environment, and can be produced during biotransformation of xenobiotics. Although the lung can be a major target for aldehyde toxicity, development of aldehyde dehydrogenases (ALDHs), which detoxify aldehydes, in lung has be...

[Scedosporium apiospermum disseminated infection in a single lung transplant recipient].

PubMed

Solé, Amparo

2011-01-01

Scedosporium spp. are filamentous fungi, and the 2 most important species are Scedosporium prolificans and Scedosporium apiospermum. S. apiospermum accounts for approximately 25% of non-Aspergillus filamentous fungi infections in organ transplant recipients. Scedosporium can colonize the sinuses and airways of lung recipients with underlying pulmonary diseases, such as bronchiectasis or cystic fibrosis before transplant, and develop invasive disease after lung transplantation. In fact, invasive diseases caused by S. apiospermum have been reported only rarely, in single lung transplant recipients and cystic fibrosis transplant patients. The treatment of scedosporiasis is complicated due to the difficulty in early diagnosis together with inherent resistance to amphotericin B. A case of disseminated S. apiospermum infection after single lung transplant in a patient with pulmonary fibrosis is reported. Leg mycetoma was the initial sign of this disseminated infection. In this case report, current treatment options are discussed, and a review of the literature of previously published cases of lung transplants is made. One conclusion based on this case is the risk of emergent molds related to antifungal prophylaxis. In addition, colonization by Scedosporium in transplant recipients should not be ignored, and target prophylaxis or suppressive therapy should be considered in all those cases with residual lesions in native lung or chronic rejection in transplanted lungs. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry

ClinicalTrials.gov

2018-02-24

Cancer, Metastatic; Cancer; Cancer of Pancreas; Cancer of Liver; Cancer of Stomach; Cancer Liver; Cancer of Rectum; Cancer of Kidney; Cancer of Esophagus; Cancer of Cervix; Cancer of Colon; Cancer of Larynx; Cancer, Lung; Cancer, Breast; Cancer, Advanced; Cancer Prostate; Cancer of Neck; Cancer of Skin; Neuroendocrine Tumors; Carcinoma; Mismatch Repair Deficiency; BRCA Gene Rearrangement; Non Hodgkin Lymphoma; Leukemia; Non Small Cell Lung Cancer; Cholangiocarcinoma; Glioblastoma; Central Nervous System Tumor; Melanoma; Urothelial Carcinoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Testicular Cancer; Breast Cancer

Donor-to-host transmission of bacterial and fungal infections in lung transplantation.

PubMed

Ruiz, I; Gavaldà, J; Monforte, V; Len, O; Román, A; Bravo, C; Ferrer, A; Tenorio, L; Román, F; Maestre, J; Molina, I; Morell, F; Pahissa, A

2006-01-01

The purpose of this study was to evaluate the incidence and etiology of bacterial and fungal infection or contamination in lung allograft donors and to assess donor-to-host transmission of these infections. Recipients who survived more than 24 h and their respective donors were evaluated. The overall incidence of donor infection was 52% (103 out of 197 donors). Types of donor infection included isolated contamination of preservation fluids (n = 30, 29.1%), graft colonization (n = 65, 63.1%) and bacteremia (n = 8, 7.8%). Donor-to-host transmission of bacterial or fungal infection occurred in 15 lung allograft recipients, 7.6% of lung transplants performed. Among these cases, 2 were due to donor bacteremia and 13 to colonization of the graft. Twenty-five percent of donors with bacteremia and 14.1% of colonized grafts were responsible for transmitting infection. Excluding the five cases without an effective prophylactic regimen, prophylaxis failure occurred in 11 out of 197 procedures (5.58%). Donor-to-host transmission of infection is a frequent event after lung transplantation. Fatal consequences can be avoided with an appropriate prophylactic antibiotic regimen that must be modified according to the microorganisms isolated from cultures of samples obtained from donors, grafts, preservation fluids and recipients.

Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer.

PubMed

Wu, Meng; Li, Hong; Liu, Ran; Gao, Xiangqian; Zhang, Menghua; Liu, Pengxing; Fu, Zheng; Yang, Jinna; Zhang-Negrerie, Daisy; Gao, Qingzhi

2016-03-03

Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had superior potency in HT29 cells compared to oxaliplatin under nontoxic dosage conditions. The dependency between cytotoxicity of Gal-Pt and glucose transporters (GLUTs) was investigated by using quercetin as an inhibitor of GLUTs in HT29 cells. The cytotoxic potency of Gal-Pt was highly reduced by the inhibitor, suggesting that the uptake of Gal-Pt was regulated by glucose transporters. The GLUT mediated transportability and cellular uptake of Gal-Pt was also demonstrated using a fluorescent glucose bioprobe in HT29 competition assay. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Engagement of Patients With Advanced Cancer

ClinicalTrials.gov

2017-05-12

End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

Sequential resection of lung metastasis following partial hepatectomy for colorectal cancer.

PubMed

Ike, H; Shimada, H; Togo, S; Yamaguchi, S; Ichikawa, Y; Tanaka, K

2002-09-01

Multiple organ metastases from colorectal carcinoma may be considered incurable, but long survival after both liver and lung resection for metastases has been reported. A retrospective analysis of 48 patients who underwent lung resection for metastatic colorectal cancer between 1992 and 1999 was undertaken. Twenty-seven patients had lung metastasis alone, 15 had previous partial hepatectomy, and six had previous resection of local or lymph node recurrence. The relationship of clinical variables to survival was assessed. Survival was calculated from the time of first pulmonary resection. Five-year survival rates after resection of lung metastasis were 73 per cent in patients without preceding recurrence, 50 per cent following previous partial hepatectomy and zero after resection of previous local recurrence. Independent prognostic variables that significantly affected survival after thoracotomy were primary tumour histology and type of preceding recurrence. There was no significant difference in survival after lung resection between patients who had sequential liver and lung resection versus those who had lung resection alone. Sequential lung resection after partial hepatectomy for metastatic colorectal cancer may lead to long-term survival.

Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

PubMed

Smith, Natalie K; Kim, Sang; Hill, Bryan; Goldberg, Andrew; DeMaria, Samuel; Zerillo, Jeron

2018-06-01

Liver transplantation (LT) is a complex procedure in a patient with multi-organ system dysfunction and coagulation defects. The surgical procedure involves dissection, major vessel manipulation, and pathophysiologic effects of graft storage and reperfusion. As a result, LT frequently involves significant hemorrhage. Subsequent massive transfusion carries high risk of transfusion-associated complications. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion associated mortality. In this case report and focused review, we present data that suggest that patients undergoing liver transplantation may be at higher risk for TRALI and TACO than the general population. Anesthesiologists can play a role in decreasing these risks by increasing recognition and reporting of TRALI and TACO, using point of care testing with thromboelastography to guide and decrease transfusion, and considering alternatives to traditional blood products like solvent/detergent plasma.

Survival from breast, colon, lung, ovarian and rectal cancer by geographical remoteness in New South Wales, Australia, 2000-2008.

PubMed

Chen, Tina Y T; Morrell, Stephen; Thomson, Wendy; Baker, Deborah F; Walton, Richard; Aranda, Sanchia; Currow, David C

2015-02-01

This study aims to compare survival from breast, colon, lung, ovarian and rectal cancer by geographical remoteness in New South Wales (NSW). Retrospective population-wide registry study. NSW, Australia. A total of 107 060 NSW residents, who were diagnosed with any of the five cancers between 01 January 2000 and 31 December 2008. Kaplan-Meier survival curves and proportional hazards regression were used to compare survival by geographical remoteness of residence at diagnosis, controlling for gender, age and extent of disease at diagnosis. Remoteness was classified using standard definitions: major city, inner regional (InnReg), outer regional (OutReg) and remote (including very remote). Significant differences in survival (likelihood of death) were identified in all five cancers: breast (adjusted hazard ratio(HR) = 1.22 (95% confidence interval (CI), 1.001-1.48) in regionalised and HR = 1.30 (1.02-1.64) in metastatic disease for OutReg areas); colon (HR = 1.14 (1.01-1.29) for OutReg areas in metastatic disease); lung (HR range = 1.08-1.35 (1.01-1.48) for most non-metropolitan areas in all stages of disease excepting regionalised); ovarian (HR = 1.32 (1.06-1.65) for OutReg areas in metastatic disease, HR = 1.40 (1.04-1.90) for InnReg areas and HR = 1.68 (1.02-2.77) for OutReg areas in unknown stage of disease) and rectal (HR = 1.37 (1.05-1.78) for OutReg areas in localised and HR = 1.14 (1.002-1.30) for InnReg areas in regionalised disease). Where significant differences were found, major cities tended to show the best survival, whereas OutReg areas tended to show the worst. Although no definitive interpretation could be made regarding remote areas due to small patient numbers, their survival appeared relatively favourable. Reasons that contribute to the differences observed and the disparate results between cancer types need to be further explored in order to facilitate targeted solutions in reducing survival inequality between NSW

Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and kidney following subchronic exposure.

PubMed

Mitra, Sumonto; Gera, Ruchi; Singh, Vikas; Khandelwal, Shashi

2014-02-01

Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to its bio-accumulative property. Isolated studies of TBT toxicity on different organs are available but consolidated information is greatly lacking. We planned this study to delineate the effect of subchronic (1 month) exposure to low dose TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration was found to be significantly increased in liver, kidney and blood, and marginally in lungs. Organo-somatic indices were seen to be altered with little effect on serum biochemical markers (liver and kidney function, and general parameters). Reactive oxygen species but not lipid peroxidation content was observed to be significantly elevated both in the tissues and serum. TBTC was found to act as a hyperlipidemic agent and it also affected heme biosynthetic pathway. Hematological analysis showed that TBTC exposure resulted in minor alterations in RBC parameters. Histological studies demonstrated marked tissue damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex-vivo conditions. Antioxidants were evidently more efficient in comparison to the calcium inhibitors, implying major role of oxidative stress pathways in TBTC toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Mold infections in lung transplants].

PubMed

Solé, Amparo; Ussetti, Piedad

2014-01-01

Invasive infections by molds, mainly Aspergillus infections, account for more than 10% of infectious complications in lung transplant recipients. These infections have a bimodal presentation: an early one, mainly invading bronchial airways, and a late one, mostly focused on lung or disseminated. The Aspergillus colonization at any time in the post-transplant period is one of the major risk factors. Late colonization, together with chronic rejection, is one of the main causes of late invasive forms. A galactomannan value of 0.5 in bronchoalveolar lavage is currently considered a predictive factor of pulmonary invasive infection. There is no universal strategy in terms of prophylaxis. Targeted prophylaxis and preemptive treatment instead of universal prophylaxis, are gaining more followers. The therapeutic drug monitoring level of azoles is highly recommended in the treatment. Monotherapy with voriconazole is the treatment of choice in invasive aspergillosis; combined antifungal therapies are only recommended in severe, disseminated, and other infections due to non-Aspergillus molds. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

[A case of obstruction due to right-sided colon cancer in which good quality of life was achieved after colonic stenting].

PubMed

Nakao, Shigetomi; Hori, Takeshi; Miura, Kotaro; Tendo, Masashige; Nakata, Bunzo; Ishikawa, Tetsuro; Hirakawa, Kosei

2013-11-01

We report a case of a 60-year-old woman with abdominal distension who was treated with self-expandable metal stent (SEMS) placement in the proximal transverse colon. She was found to have severe bowel obstruction due to advanced transverse colon cancer on plain computed tomography (CT) and colonoscopy. We performed colonic stenting safely, and the symptom promptly improved. Defecation and flatus were observed on the same day of stenting, and the patient was able to start drinking and eating on the next day. Enhanced abdominal CT revealed multiple liver metastasis, peritoneal dissemination, ascites, and cystic ovarian tumor. After treatment with 1 course of 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6), the patient was discharged on day 14 after admission. The rapidly enlarging ovarian tumors and primary colonic lesion with SEMS were surgically removed after treatment with mFOLFOX6 for 4 months in an outpatient basis. The patient has been alive with a good quality of life (QOL) and being treated with bevacizumab plus mFOLFOX6/Leucovorin, 5-fluorouracil, and irinotecan( FOLFIRI) for 6 months. SEMS placement could be safe and effective for the treatment of obstruction of the right colon, and could maintain a good QOL in patients.

Comparison of clinical and laboratory findings between those with pulmonary tuberculosis and those with nontuberculous mycobacterial lung disease.

PubMed

Thanachartwet, Vipa; Desakorn, Varunee; Duangrithi, Duangjai; Chunpongthong, Pongsak; Phojanamongkolkij, Kamol; Jitruckthai, Pasakorn; Kasetjaroen, Yuttichai; Pitisuttithum, Punnee

2014-01-01

In tuberculosis endemic areas, patients with sputum positive for acid-fast bacilli (AFB) are usually diagnosed and treated for pulmonary tuberculosis. The diagnosis of nontuberculous mycobacteria (NTM) lung disease is often ascertained only after lung disease progression occurs, increasing the risk of severe morbidity and mortality. We conducted a matched case-control study among a prospective cohort of 300 patients with newly diagnosed AFB-positive sputum in Thailand during 2010-2012. We compared clinical and laboratory parameters and outcomes among patients with pulmonary tuberculosis, NTM lung disease and NTM colonization. A mycobacterial culture was performed in all patients. Ten patients with NTM lung disease were compared to 50 patients with pulmonary tuberculosis and 10 patients with NTM colonization. The presence of diabetes mellitus or human immunodeficiency virus infection, were associated with NTM lung disease (p = 0.030). Patients with NTM lung disease had a significantly lower body weight prior to treatment (p = 0.021), a higher body weight change from baseline (p = 0.038), and were more likely to have cavitations on chest radiograph (p = 0.033) than those with NTM colonization. In tuberculosis endemic areas, mycobacterial identification should be performed among patients with impaired immune function. NTM lung disease treatment should be considered in patients with NTM sputum isolates who have a history of significant weight loss or cavitations on chest radiography.

Imaging Nuclear-Cytoplasmic Dynamics in Primary and Metastatic Colon Cancer in Nude Mice.

PubMed

Hasegawa, Kosuke; Suetsugu, Atsushi; Nakamura, Miki; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Bouvet, Michael; Shimizu, Masahito; Hoffman, Robert M

2016-05-01

Colon cancer frequently results in metastasis to the liver, where it becomes the main cause of death. However, the cell cycle in primary tumors and metastases is poorly understood. We developed a mouse model of liver metastasis using the human colon cancer cell line HCT-116, which expresses green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (HCT-116-GFP-RFP). HCT-116 GFP-RFP cells were injected into the spleen of nu/nu nude mice. HCT-116-GFP-RFP cells subsequently formed primary tumors in the spleen, as well as metastatic colonies in the liver and retroperitoneum by 28 days after cell transplantation. Using an Olympus FV1000 confocal microscope, it was possible to clearly image mitosis of the dual-colored colon cancer cells in the primary tumor as well as liver and other metastases. Multi-nucleate cancer cells, in addition to mono-nucleate cancer cells and their mitosis, were observed in the primary tumor and metastasis. Multi-nucleate HCT-116-GFP-RFP cells were also observed after culture of the primary and metastatic tumors. A similar ratio of mono-nucleate, multi-nucleate, and mitotic cells grew from the primary and metastatic tumors in culture, suggesting similarity of the nuclear-cytoplasmic dynamics of primary and metastatic cancer cells, further emphasizing the stochastic nature of metastasis. Our results demonstrate a similar heterogeneity of nuclear-cytoplasmic dynamics within primary tumors and metastases, which may be an important factor in the stochastic nature of metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Burden of Cancer in Korea during 2012: Findings from a Prevalence-Based Approach.

PubMed

Gong, Young Hoon; Yoon, Seok Jun; Jo, Min Woo; Kim, Arim; Kim, Young Ae; Yoon, Jihyun; Seo, Hyeyoung; Kim, Dongwoo

2016-11-01

Cancer causes a significant deterioration in health and premature death and is a national socioeconomic burden. This study aimed to measure the burden of cancer using the disability-adjusted life year (DALY) metric based on the newly adopted methodology from the Global Burden of Disease Study in 2010. This study was conducted based on data from the Korean National Cancer Registry. The DALYs were calculated using a prevalence-based method instead of the incidence-based method used by previous studies. The total burden of cancer in 2012 was 3,470.79 DALYs per 100,000 persons. Lung cancer was the most prevalent cancer burden, followed by liver, stomach, colorectal, and breast cancer. The DALYs for lung, liver, stomach, colon and rectum, and pancreatic cancer were high in men, whereas the DALYs for breast, lung, stomach, colorectal, and liver cancer were high in women. Health loss from leukemia and cancer of the brain and nervous system was prevalent for those younger than age 20; from stomach, breast, and liver for those aged 30-50; and from lung, colon and rectum, and pancreas for a large proportion of individuals over the age of 60. The most important differences were that the DALYs were calculated by prevalence and that other components of the DALYs were measured by a population-based perspective. Thus, prevalence-based DALYs could provide more suitable data for decision making in the healthcare field.

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

ClinicalTrials.gov

2018-06-15

Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe₃O₄-PEG-GA) Against Lung, Breast and Colon Cancer Cells.

PubMed

Rosman, Raihana; Saifullah, Bullo; Maniam, Sandra; Dorniani, Dena; Hussein, Mohd Zobir; Fakurazi, Sharida

2018-02-02

Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.

Lung Cancer Rates by Race and Ethnicity

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Rates by Race and Ethnicity for Other Kinds of Cancer All Cancers Combined Breast Cervical Colorectal (Colon) HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by Race and Ethnicity Language: ...

[Suppression of the growth of subcutaneous transplanted human liver cancer and lung metastasis in nude mice treated by sorafenib combined with fluorouracil].

PubMed

Shen, Hu-jia; Wang, Yan-hong; Xu, Jian

2013-02-01

The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice, and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu. The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells, and the tumor-bearing nude mice were treated with sorafenib, 5-Fu or both, respectively, and mock-treated tumor-bearing nude mice as negative control. To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases. Moreover, the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK), P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo IIa) in the nude mice were assayed by immunocytochemistry and Western blot. The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group, (0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group, (0.786 ± 0.212) g and 5.429 ± 4.315 in the Sorafenib + 5-Fu combination group, and (2.438 ± 0.793) g and 10.429 ± 6.241 in the 5-Fu group. Statistically, the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased, compared with that in the control group (P < 0.05). There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P > 0.05). The expression levels of p-ERK, P-gp and Topo IIa proteins in the tumors after normalization were: negative control (0.017 ± 0.010, 0.085 ± 0.012, 0.103 ± 0.093), sorafenib group (0.010 ± 0.008, 0.044 ± 0.020, 0.020 ± 0.018), combination group (0.011 ± 0.007, 0.043 ± 0.023, 0.062 ± 0.026), and 5-Fu group (0.018 ± 0.009, 0.063 ± 0.032, 0.065 ± 0.034), respectively. Statistically, the expression of p-ERK, P-gp and Topo

Pentraxin 3 levels in bronchoalveolar lavage fluid of lung transplant recipients with invasive aspergillosis.

PubMed

Kabbani, Dima; Bhaskaran, Archana; Singer, Lianne G; Bhimji, Alyajahan; Rotstein, Coleman; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

2017-09-01

Invasive aspergillosis is the most common invasive fungal infection in lung transplant recipients. The use of galactomannan testing in bronchoalveolar lavage (BAL) fluid has improved diagnosis of invasive aspergillosis; however, false-positive results can lead to overdiagnosis and unnecessary treatment. The use of proinflammatory markers such as pentraxin 3 (PTX3) may help differentiate between Aspergillus colonization and disease. BAL PTX3 concentrations were measured by enzyme-linked immunosorbent assay in 151 lung transplant recipients and 9 healthy control subjects. Patients were characterized as having Aspergillus colonization or invasive disease according to International Society of Heart and Lung Transplantation criteria. Concomitant PTX3values were compared using Mann-Whitney U and Kruskal-Wallis tests. We analyzed 322 BAL stored samples and identified 15 invasive aspergillosis events, 38 Aspergillus colonizations, and 17 positive galactomannan with negative Aspergillus cultures. Median BAL PTX3 level was significantly higher in patients with invasive aspergillosis compared with patients with Aspergillus colonization and healthy control subjects (439.20 pg/ml [interquartile range (IQR) 168.18-778.90], 68.93 pg/ml [IQR 13.67-156.74], and 13.67 pg/ml [IQR 13.67-121.18]; p < 0.001). Patients with BAL PTX3 value >319 pg/ml with positive galactomannan and patients with BAL PTX3 value >312 pg/ml with positive Aspergillus culture were 4.5 and 5.5 times more likely to have invasive pulmonary aspergillosis, respectively. Our study shows that PTX3 measurements in BAL samples were significantly higher among patients with invasive aspergillosis and may help to identify patients with Aspergillus colonization and false-positive galactomannan in BAL samples. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Inhibition of histone deacetylases by trans-cinnamic acid and its antitumor effect against colon cancer xenografts in athymic mice

PubMed Central

ZHU, BINGYAN; SHANG, BOYANG; LI, YI; ZHEN, YONGSU

2016-01-01

Previous studies have shown that trans-cinnamic acid (tCA) has a broad spectrum of biological activities, and exhibits antioxidant, anti-inflammatory and anticancer properties. In addition, tCA and a variety of its analogs have been detected as gut microbe-derived metabolites exerting various biological effects in the colon. The aim of this study was to assess the antitumor activity of tCA in vitro and in vivo, in particular its therapeutic efficacy against colon cancer xenografts in athymic mice. Furthermore, it aimed to examine the effects of tCA on histone deacetylases (HDACs) and to identify the underlying molecular mechanisms. Using an MTT assay, tCA was observed to inhibit the proliferation of several cancer cell lines, and the half maximal inhibitory concentration (IC50) in HT29 colon carcinoma cells was ~1 mM. Western blot analysis demonstrated that tCA upregulated the expression of acetyl-H3 and acetyl-H4 proteins, which was consistent with the effects of the HDAC inhibitor, trichostatin A (TSA). Furthermore, expression of Bcl-2 (a marker of cell proliferation) was reduced, and apoptosis was induced. Apoptosis was shown by the activation of cleavage of poly ADP ribose polymerase and the increased expression of Bax. Apoptosis was also confirmed using APC Annexin V and SYTOX Green Nucleic Acid Stain. In addition, the tCA-induced inhibition of the expression of HDAC markers and activation of apoptosis in tumor tissues were further confirmed by immunohistochemistry. Intragastric administration of tCA at doses of 1.0 and 1.5 mmol/kg body weight suppressed the growth of HT29 human colon carcinoma xenografts in athymic mice at well-tolerated doses. No toxic changes were found in the heart, lung, liver, kidney, colon or bone marrow following histopathological examination. This study indicated that tCA is effective against colon cancer xenograft in nude mice. The antitumor mechanism of tCA was mediated, at least in part, by inhibition of HDACs in cancer cells. As

Lung uptake of /sup 99m/Tc--sulfur colloid in falciparum malaria: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziessman, H.A.

Increased lung uptake of /sup 99m/Tc-sulfur colloid was seen during liver scanning in a patient with falciparum malaria. This finding was due to the enhanced activity of the phagocytic cells of the reticuloendothelial system in the liver, spleen, and lung found in human and experimental malaria. Similar findings in other clinical situations and the relevant literature are reviewed.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.

PubMed

Simpson, Kathleen E; Esmaeeli, Amir; Khanna, Geetika; White, Francis; Turnmelle, Yumirle; Eghtesady, Pirooz; Boston, Umar; Canter, Charles E

2014-02-01

Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population. © 2014 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

PubMed Central

Diggs, Deacqunita L.; Myers, Jeremy N.; Banks, Leah D.; Niaz, Mohammad S.; Hood, Darryl B.; Roberts, L. Jackson; Ramesh, Aramandla

2013-01-01

In the US alone, around 60,000 lives/year are lost due to colon cancer. Diet and environment have been implicated in the development of sporadic colon tumors. The objective of this study was to determine how dietary fat potentiates the development of colon tumors through altered B(a)P biotransformation, using the Adenomatous polyposis coli with Multiple intestinal neoplasia mouse model. Benzo(a)pyrene was administered to mice through tricaprylin, and unsaturated (USF; peanut oil) and saturated (SF; coconut oil) fats at doses of 50 and 100 μg/kg via oral gavage over a 60-day period. Blood, colon, and liver were collected at the end of exposure period. The expression of B(a)P biotransformation enzymes [cytochrome P450 (CYP)1A1, CYP1B1 and glutathione-S-transferase] in liver and colon were assayed at the level of protein, mRNA and activities. Plasma and tissue samples were analyzed by reverse phase high-performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose-dependent manner, with 100 μg/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater concentration of B(a)P metabolites, compared to the 50 μg/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen. PMID:24231098

Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure.

PubMed

Nedredal, Geir I; Elvevold, Kjetil; Chedid, Marcio F; Ytrebø, Lars M; Rose, Christopher F; Sen, Sambit; Smedsrød, Bård; Jalan, Rajiv; Revhaug, Arthur

2016-01-01

Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.

Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis

PubMed Central

Masri, Selma; Papagiannakopoulos, Thales; Kinouchi, Kenichiro; Liu, Yu; Cervantes, Marlene; Baldi, Pierre; Jacks, Tyler; Sassone-Corsi, Paolo

2016-01-01

SUMMARY The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous zeitgebers, such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock, but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK and SREBP signaling, leading to altered insulin, glucose and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PMID:27153497

A case of lung abscess successfully treated by transbronchial drainage using a guide sheath.

PubMed

Izumi, Hiroki; Kodani, Masahiro; Matsumoto, Shingo; Kawasaki, Yuji; Igishi, Tadashi; Shimizu, Eiji

2017-05-01

A 51-year-old man was diagnosed with colon cancer in September 2011, and a solitary pulmonary nodule was detected by computed tomography (CT) scan. We performed a transbronchial biopsy with endobronchial ultrasonography using a guide sheath (GS) and diagnosed lung metastasis of colon cancer. The patient experienced remittent fever after the biopsy in spite of intravenous antibiotic therapies. Moreover, his CT scan showed a large lung abscess at the biopsy site. We performed transbronchial drainage using a GS as salvage therapy. The bloody pus was successfully aspirated, and chest X-ray following the procedure showed dramatic shrinkage of the abscess.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

PubMed

Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

A squamous cell lung carcinoma with abscess-like distant metastasis.

PubMed

Dursunoğlu, Neşe; Başer, Sevin; Evyapan, Fatma; Kiter, Göksel; Ozkurt, Sibel; Polat, Bahattin; Karabulut, Nevzat

2007-01-01

This is a metastatic spread of squamous cell lung carcinoma to lungs, liver, lymph node, bone and subcutanous region as multiple abscess-like lesions. A fifty-five years old man admitted to the out-patient clinic with fever, cough, hemopthysis, night sweats, chest pain, abdominal pain and weight loss. In a short period of time abcess like lesions developed in his lungs, liver, lymph node, bone and subcutanous region. Though the clinical presentation is suggestive for an infectious condition, no success to antimicrobial treatment and negative results of microbiological studies have arised a need to further investigations. Histopathological studies of the abscess wall ultimately gave the definitive diagnosis as metastatic squamous cell carcinoma. We believe that case report is interesting because of the uncommon metastatic lesions masquerading the abscesses and also wide-spread multiple distant invasions of a squamous cell lung carcinoma in a short time period.

[Graft-versus-host disease, a rare complication of lung transplantation].

PubMed

Morisse-Pradier, H; Nove-Josserand, R; Philit, F; Senechal, A; Berger, F; Callet-Bauchu, E; Traverse-Glehen, A; Maury, J-M; Grima, R; Tronc, F; Mornex, J-F

2016-02-01

Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Benzylmorpholine Analogs as Selective Inhibitors of Lung Cytochrome P450 2A13 for the Chemoprevention of Lung Cancer in Tobacco Users

PubMed Central

Blake, Linda C.; Roy, Anuradha; Neul, David; Schoenen, Frank J.; Aubé, Jeffrey; Scott, Emily E.

2013-01-01

Purpose 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), one of the most prevalent and procarcinogenic compounds in tobacco, is bioactivated by respiratory cytochrome P450 (CYP) 2A13, forming DNA adducts and initiating lung cancer. CYP2A13 inhibition offers a novel strategy for chemoprevention of tobacco-associated lung cancer. Methods Twenty-four analogs of a 4-benzylmorpholine scaffold identified by high throughput screening were evaluated for binding and inhibition of both functional human CYP2A enzymes, CYP2A13 and the 94%-identical hepatic CYP2A6, whose inhibition is undesirable. Thus, selectivity is the major challenge in compound design. Results A key feature resulting in CYP2A13-selective binding and inhibition was substitution at the benzyl ortho position, with three analogs being >25-fold selective for CYP2A13 over CYP2A6. Conclusions Two such analogs were negative for genetic and hERG toxicities and metabolically stable in human lung microsomes, but displayed rapid metabolism in human liver and in mouse and rat lung and liver microsomes, likely due to CYP2B-mediated degradation. A specialized knockout mouse mimicking the human lung demonstrates compound persistence in lung and provides an appropriate test model. Compound delivered by inhalation may be effective in the lung but rapidly cleared otherwise, limiting systemic exposure. PMID:23756756

Triflavin, an Arg‐Gly‐Asp‐containing Antiplatelet Peptide Inhibits Cell‐substratum Adhesion and Melanoma Cell‐induced Lung Colonization

PubMed Central

Sheu, Joen R.; Lin, Chao H.; Chung, Jih L.; Teng, Che M.

1992-01-01

Triflavin, an Arg‐Gly‐Asp (RGD) containing peptide purified from Trimeresurus flavoviridis snake venom, inhibits human platelet aggregation by blocking fibrinogen binding to fibrinogen receptors associated with glycoprotein Ilb/IIIa complex. In this study, we show that triflavin (1‐30 μg/mouse) inhibits B16‐F10 melanoma cell‐induced lung colonization in C57BL/6 mice in a dose‐dependent manner. In vitro, triflavin dose‐dependently inhibits adhesion of B16‐F10 melanoma cells to extracellular matrices (ECMs; i.e., fibronectin, fibrinogen, vitronectin, and collagen type I). Triflavin is approximately 600‐800 times more potent than GRGDS at inhibiting cell adhesion. In addition, triflavin dose‐dependently inhibits B16‐F10 cell‐induced platelet aggregation. These results imply that the inhibitory effect of triflavin on the adhesion of tumor cells to ECMs (e.g., fibronectin, vitronectin and collagen type I) and/or tumor cell‐induced platelet aggregation may be partially responsible for its antimetastatic activity in C57BL/6 mice. PMID:1399825

Circulating tumor cells in lung cancer.

PubMed

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.

Metabolic inactivation of five glycidyl ethers in lung and liver of humans, rats and mice in vitro.

PubMed

Boogaard, P J; de Kloe, K P; Bierau, J; Kuiken, G; Borkulo, P E; Watson, W P; van Sittert, N J

2000-05-01

1. Some glycidyl ethers (GE) have been shown to be direct mutagens in short-term in vitro tests and consequently GE are considered to be potentially mutagenic in vivo. However, GE may be metabolically inactivated in the body by two different enzymatic routes: conjugation of the epoxide moiety with the endogenous tripeptide glutathione (GSH) catalysed by glutathione S-transferase (GST) or hydrolysis of the epoxide moiety catalysed by epoxide hydrolase (EH). 2. The metabolic inactivation of five different GE, the diglycidyl ethers of bisphenol A (BADGE), 4,4'-dihydroxy-3,3',5,5'-tetramethylbiphenyl (Epikote YX4000) and 1,6-hexanediol (HDDGE) and the GE of 1-dodecanol (C12GE) and o-cresol (o-CGE), has been studied in subcellular fractions of human, C3H mouse and F344 rat liver and lung. 3. All GE were chemically very stable and resistant to aqueous hydrolysis, but were rapidly hydrolysed by EH in cytosolic and microsomal fractions of liver and lung. The aromatic GE were very good substrates for EH. In general, microsomal EH is more efficient than cytosolic EH in hydrolysis of GE, and human microsomes are more efficient than rodent microsomes. 4. The more water-soluble GE, o-CGE and HDDGE, were good substrates for GST whereas the more lipophilic GE, YX4000 and C12GE, were poor substrates for GST. In general, rodents are more efficient in GSH conjugation of GE than humans. 5. In general, the epoxide groups of YX4000 are the most and those of HDDGE the least efficiently inactivated of the five GE under study. For the other three GE no general trend was observed: the relative efficiency of inactivation varied with organ and species. 6. The large variation in metabolism observed with five representative GE indicate that GE have variable individual properties and should not be considered as a single, homogenous class of compounds.

The impact of pan-resistant bacterial pathogens on survival after lung transplantation in cystic fibrosis: results from a single large referral centre.

PubMed

Dobbin, C; Maley, M; Harkness, J; Benn, R; Malouf, M; Glanville, A; Bye, P

2004-04-01

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Spectroscopy With Surface Coils and Decoupling

ClinicalTrials.gov

2015-12-23

Adrenal Cortical Cancer; Brain Cancer; Breast Cancer; CNS Cancer; Colon Cancer; HEENT Cancer; Hodgkin's Disease; Kaposi's Sarcoma; Liver Cancer; Lung Cancer; Non-Hodgkin's Lymphoma; Ovarian Cancer; Pancreatic Cancer; Prostate Cancer; Rectal Cancer; Renal Cancer; Sarcoma; Squamous Cell Carcinoma; Thyroid Cancer

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Magnetic Resonance Imaging of Liver Metastasis.

PubMed

Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Carcinoma transverse colon masquerading as carcinoma gall bladder

PubMed Central

Kumar, Ashwani; Singh, Harnam; Singh, Gurpreet; Singh, Bimaljot; Chauhan, Mahak

2014-01-01

Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications. PMID:24772345

Carcinoma transverse colon masquerading as carcinoma gall bladder.

PubMed

Munghate, Anand; Kumar, Ashwani; Singh, Harnam; Singh, Gurpreet; Singh, Bimaljot; Chauhan, Mahak

2014-04-01

Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications.

POP exposure from fish liver consumption and risk of cancer--the Norwegian Women and Cancer Study.

PubMed

Brustad, Magritt; Sandanger, Torkjel Manning; Andersen, Vegard; Lund, Eiliv

2007-07-01

The aim of the study was to investigate the hypothesis that consumption of fish liver increases cancer risk in humans due to increased intake of persistent organic pollutants (POPs). This study is based on data from the Norwegian Women and Cancer Study (NOWAC). The study has a prospective cohort design with questionnaire data from 64 285 randomly selected Norwegian women (aged 40-70 at baseline) and linkage to the Norwegian Cancer Registry. Cox proportional hazards regression was used to calculate risk ratios associated with consumption of fish liver and total cancer and cancer in breast, uterus, and colon. Fish liver consumption was, after adjusting for known risk factors, associated with a significant reduced risk for total cancer (RR = 0.92, 95% CI: 0.85, 0.99), and non-significant reduced risk for breast cancer (RR = 0.90, 95% CI: 0.78, 1.04), and colon cancer (RR = 0.82, 95% CI: 0.63, 1.07). Relative risk for uterus cancer was 0.82 (95% CI: 0.61-1.12). No significant dose-response effect was found for frequency of fish liver consumption (when divided into three intake groups) and total cancer, nor for any of the other cancer sites.We have concluded that in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found.

Inhibition of nitric oxide production and the effects of arginine and Lactobacillus administration in an acute liver injury model.

PubMed

Adawi, D; Molin, G; Jeppsson, B

1998-12-01

To study the effect of inhibiting nitric oxide production and the effects of arginine and lactobacilli administration in an acute liver injury (LI) model. Infectious complications caused by enteric bacteria are common in patients with liver diseases and those who have undergone liver surgery. Increased bacterial translocation has been proposed as one underlying mechanism. Lactobacilli constitute an integral part of the normal gastrointestinal microecology; they are involved in host metabolism and have many beneficial properties. Arginine has numerous roles in cellular metabolism and may be metabolized by lactobacilli in some cases. We have previously shown that rectal administration of Lactobacillus plantarum DSM 9843 (strain 299v), with and without arginine, in an acute LI model significantly reduces the extent of the LI and reduces bacterial translocation. To clarify the pathogenetic mechanisms, we studied the role of nitric oxide in the effects of L. plantarum and arginine in acute LI, as determined by bacterial translocation, ileal, cecal, and colonic nucleotides, RNA, and DNA. Male Sprague-Dawley rats were used. L. plantarum, 2% arginine, and/or N-nitro-L-arginine methyl ester (L-NAME), as appropriate, were administered rectally once daily for 8 days. Acute LI was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples were collected after 24 hours. Bacterial translocation was evaluated by culture of portal and arterial blood, mesenteric lymph nodes, and liver tissue. Liver enzymes and bilirubin were assayed in the serum. The bacterial load in the cecum and colon was determined. Ileal, cecal, and colonic mucosal nucleotides, RNA, and DNA were evaluated. The levels of liver enzymes and bilirubin were lower in liver-injured rats supplemented with arginine and Lactobacillus, and this effect was abolished by the addition of L-NAME. Inhibition of nitric oxide production (by L-NAME) increased bacterial

Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-03-07

Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Tumors Metastatic to Brain

A case of synchronous metastasis of breast cancer to stomach and colon.

PubMed

Takeuchi, Hideya; Hiroshige, Shozi; Yoshikawa, Yasuji; Kusumoto, Tetusya; Muto, Yoichi

2012-09-01

A case of synchronous metastasis of breast cancer to the stomach and colon is reported. A 38-year-old woman with a history of bilateral breast cancer was admitted for endoscopic examination because of occult blood. Endoscopic examination showed elevated lesions on the mucosal surface of the stomach and cecum. Histopathological examination of the biopsy specimens obtained from both sites showed adenocarcinoma, comprised of tumor cells with structural and nuclear atypia, which were similar to those of the primary breast cancer cells. In immunohistochemical analysis, these tumor cells stained positive for ER. Therefore, we diagnosed a synchronous metastasis of breast cancer to the stomach and colon. Synchronous metastasis of breast cancer to the stomach and colon without liver metastasis or peritoneal dissemination is extremely rare, with only 4 reported cases existing in literature.

Experimental splenosis in the liver and lung spread through the vasculature.

PubMed

Seguchi, S; Yue, F; Asanuma, K; Sasaki, K

2015-05-01

To demonstrate that intra-organ splenosis can engraft and develop after being distributed through the vasculature, tiny fragments of splenic tissues were injected into the inferior vena cava or the portal vein to induce intrapulmonary and intrahepatic splenosis in rats. After 1 month, splenic autograft structures in the lung and liver were assessed for structure by histology, for immunologic compartments by immunohistochemistry, for phagocytic function by carbon uptake and for vascular formation by Microfil (a silicon rubber compound) injection. Intrapulmonary and intrahepatic splenoses were indeed able to spread through the vasculature. The intrapulmonary splenic autografts were trapped and spread out in the interstitium, without forming a capsule. White pulp was markedly developed, showing lymphocyte aggregations that consisted in B cells surrounding the dilated vessel. Splenic sinuses were not definitively observed. Although macrophages were detected by immunohistochemistry, they showed no indication of having phagocytized carbon particles from the vessels, implying a closed circulation. In contrast, intrahepatic splenic autografts formed well-developed capsules, trabeculae and red pulp with splenic sinuses. Macrophages detected by immunohistochemistry were observed capturing carbon particles, which clearly revealed an open system circulation, as seen in normal rat spleen. The development of white pulp was poor and lymphocytes consisting in B cells aggregated in the peripheral margins. These results demonstrate that intra-organ splenosis can spread through the vasculature and that the morphologic and immunologic structures formed in these regenerated autografts are influenced by the organ vasculature and extracellular matrix wherein the tissue fragments settled.

Oxidant/antioxidant status in lambs and sheep with liver and lung cystic echinococcosis diagnosed by ultrasonography and necropsy.

PubMed

Sagkan-Ozturk, A; Durgut, R; Ozturk, O H

2015-03-15

The aim of this study was to evaluate total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in sheep and lambs with cyctic eccinocoocosis (CE) diagnosed by ultrasonography and necropsy findings. A total of 9 sheep and 17 lambs with CE were used in this study and the findings were compared to those of 6 healthy control sheep. Ultrasonography were used for the diagnosis of CE in sheep and lambs, and necropsy was performed to check the presence of cysts in liver and lungs. Serum TOS and TAC were measured by a novel colorimetric method. The TOS-to-TAC ratios were also calculated as OSI values. Serum biochemical profiles were determined by conventional measurement methods as well. The mean values for TOS, TAC and OSI were significantly (p<0.001) lower in sheep and lambs with CE when compared with those of the control sheep, and they were also significantly lower in lambs with CE in comparison to the mean values obtained in sheep with CE. The levels of serum albumin, total cholesterol, creatinine, and triglycerides in lambs with CE were found out to decrease significantly (p<0.001) when compared with those of both sheep with EC and the control group. There were no significant differences between the groups in terms of other serum parameters. In addition, when clinically and some biochemical values were evaluated, CE was found to be more severe in lambs than in sheep. It was concluded that although common diagnostic cyst detection is performed by postmortem examination, ultrasonography could successfully be used in conjunction with serum biochemical profile detection and serum TOS, TAC and OSI measurements for diagnosis of cysts in liver and lungs of severely infected living sheep and lambs. Serum albumin, total cholesterol, creatinine, total protein and triglycerides might be used as indicators in sheep and particularly in lambs for the diagnosis of CE. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardiac-Sparing Whole Lung IMRT in Children With Lung Metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalapurakal, John A., E-mail: j-kalapurakal@northwestern.edu; Zhang, Yunkai; Kepka, Alan

Purpose: To demonstrate the dosimetric advantages of cardiac-sparing (CS) intensity modulated radiation therapy (IMRT) in children undergoing whole lung irradiation (WLI). Methods and Materials: Chest CT scans of 22 children who underwent simulation with 3-dimensional (n=10) or 4-dimensional (n=12) techniques were used for this study. Treatment planning was performed using standard anteroposterior-posteroanterior (S-RT) technique and CS-IMRT. Left and right flank fields were added to WLI fields to determine whether CS-IMRT offered any added protection to normal tissues at the junction between these fields. The radiation dose to the lung PTV, cardiac structures, liver, and thyroid were analyzed and compared. Results:more » CS-IMRT had 4 significant advantages over S-RT: (1) superior cardiac protection (2) superior 4-dimensional lung planning target volume coverage, (3) superior dose uniformity in the lungs with fewer hot spots, and (4) significantly lower dose to the heart when flank RT is administered after WLI. Conclusions: The use of CS-IMRT and 4-dimensional treatment planning has the potential to improve tumor control rates and reduce cardiac toxicity in children receiving WLI.« less

Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report.

PubMed

Shafii, A E; Harris, D D; Baz, M

2017-09-01

Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies.

PubMed

Darby, S C; Whitley, E; Howe, G R; Hutchings, S J; Kusiak, R A; Lubin, J H; Morrison, H I; Tirmarche, M; Tomásek, L; Radford, E P

1995-03-01

Exposure to the radioactive gas radon and its progeny (222Rn and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64,209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

Colonic intussusception in descending colon: An unusual presentation of colon lipoma

PubMed Central

Bagherzadeh Saba, Reza; Sadeghi, Amir; Rad, Neda; Safari, Mohammad Taghi; Barzegar, Farnoush

2016-01-01

Lipomas of the colon are relatively rare benign soft tissue tumors derived from mature adipocytes of mesenchymatic origin. During colonoscopy, surgery or autopsy they are generally discovered incidentally. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, in the cases with larger in size of tumor some symptoms such as anemia, abdominal pain, constipation, diarrhea, bleeding, or intussusception may be presented. We reported a 47-year-old woman with colonic intussusception in the descending colon caused by colonic lipoma and diagnosed after surgical exploration for obstructive colonic mass. PMID:28224035

Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: a prospective trial with different detection techniques.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Das, Avisnata; Harouaka, Ramdane A; Dicker, David T; Li, Guangfu; Zhu, Junjia; Clawson, Gary A; Yang, Zhaohai; Reed, Michael F; Gusani, Niraj J; Kimchi, Eric T; Staveley-O'Carroll, Kevin F; Zheng, Si-Yang; El-Deiry, Wafik S

2015-01-01

Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. 25 CRC patients undergoing liver (16 (64%)) or lung (9 (36%)) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch® system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch®'s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick®). CTC numbers peaked during the resection with the FMSA in contrast to CellSearch® (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch®: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0-101) than CellSearch® (range 0-9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch® system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.

Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

ClinicalTrials.gov

2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Primary Hepatocellular Carcinoma; Adult Subependymoma; Advanced Adult Primary Liver Cancer; Advanced Malignant Mesothelioma; Male Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Malignant Mesothelioma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage II Esophageal Cancer; Stage II Pancreatic Cancer; Stage III Esophageal Cancer

How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non-Colorectal Liver Metastases?

PubMed Central

Vogl, Thomas J.; Emam, Ahmed; Naguib, Nagy N.; Eichler, Katrin; Zangos, Stefan

2015-01-01

Summary Background The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. Methods Liver-directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: ‘image-guided tumor ablation’, ‘thermal ablation therapies’, ‘liver metastases of uveal melanoma’, ‘neuroendocrine carcinoma’, ‘breast cancer’, and ‘non-colorectal liver metastases’. Results Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. Conclusion Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID:26889144

Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What is the Effect of Direct Beta Irradiation?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobrocky, Tomas, E-mail: tomas.dobrocky@insel.ch; Fuerstner, Markus, E-mail: markus.fuerstner@insel.ch; Klaeser, Bernd, E-mail: bernd.klaeser@insel.ch

2015-08-15

We herein present a patient undergoing selective internal radiation therapy with an almost normal lung shunt fraction of 11.5 %, developing histologically proven radiation pneumonitis. Due to a predominance of pulmonary consolidations in the right lower lung and its proximity to a large liver metastases located in the dome of the right liver lobe a Monte Carlo simulation was performed to estimate the effect of direct irradiation of the lung parenchyma. According to our calculations direct irradiation seems negligible and RP is almost exclusively due to ectopic draining of radioactive spheres.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

PubMed

Salah, Samer; Ardissone, Francesco; Gonzalez, Michel; Gervaz, Pascal; Riquet, Marc; Watanabe, Kazuhiro; Zabaleta, Jon; Al-Rimawi, Dalia; Toubasi, Samar; Massad, Ehab; Lisi, Elena; Hamed, Osama H

2015-01-01

Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

ClinicalTrials.gov

2015-09-28

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

Polysaccharide from seeds of Plantago asiatica L. affects lipid metabolism and colon microbiota of mouse.

PubMed

Hu, Jie-Lun; Nie, Shao-Ping; Wu, Qi-Meng; Li, Chang; Fu, Zhi-Hong; Gong, Joshua; Cui, Steve W; Xie, Ming-Yong

2014-01-08

Polysaccharide from the seeds of Plantago asiatica L. was given via oral administration to mice (0.4 g/kg body weight, 30 days) to observe its effects on mouse nutrient metabolism and colon microbiota. It was found the polysaccharide intake could lower the apparent absorption of lipid. Total triglyceride, cholesterol, and atherogenic index in blood serum with total lipid and cholesterol levels in liver of polysaccharide group mice were all significantly lower than those of the control group (p < 0.05). Furthermore, the effect of the polysaccharide intake on mouse colon bacterial communities was investigated. Mice from the polysaccharide group showed a higher colon bacterial diversity than the control group. Bacteroides sp., Eubacterium sp., butyrate-producing bacteria Butyrivibrio sp., and probiotics Bifidobacterium bifidum , Lactobacillus fermentum , and Lactobacillus reuteri in mouse colon were all increased after polysaccharide intake. These indicated that the intake of polysaccharide from P. asiatica L. could be beneficial for lipid metabolism and colon microbiota.

Colonic perforation with peritonitis in amoebiasis: a tropical disease with high mortality.

PubMed

Jain, Bhupendra Kumar; Garg, Pankaj Kumar; Kumar, Anjay; Mishra, Kiran; Mohanty, Debajyoti; Agrawal, Vivek

2013-01-01

Invasive colonic amoebiasis presents primarily with dysentery; colonic perforation occurs rarely. Cases of amoebic colonic perforations have been reported sporadically over the past 20 years. A retrospective study was done in the surgical unit of a tertiary care hospital in North India. The case records of those patients were reviewed who underwent exploratory laparotomy from January 2011 to September 2012 and were diagnosed with amoebic colonic perforation on histopathological examination. Details concerning the clinical presentation, investigations, intraoperative findings, operative procedures, and postoperative outcomes were retrieved. Amongst, a total of 186 emergency exploratory laparotomies carried out during the study, 15 patients of amoebic colonic perforation were identified. The median age of the patients was 42 years (IQR 32.0-58.0) and the male to female ratio was 13:2. Previous history of colitis was present in only 1 patient. The preoperative diagnosis was perforation peritonitis in 12 patients; and intussusception, intestinal obstruction and ruptured liver abscess in 1 patient each. Ten patients had single perforation while 5 had multiple colonic perforations. All the patients except one had perforations in the right colon. Bowel resection was performed depending upon the site and extent of the colon involved-right hemicolectomy (8), limited ileocolic resection (6) and sigmoidectomy (1). Bowel continuity could be restored only in 2 of the 15 patients and a stoma was constructed in the remaining 13 patients. The overall mortality rate was found to be 40% (6/15). Amoebic colonic perforation is associated with unusually high mortality.

Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F.

PubMed

Oliveira, Amanda; Beyer, Georg; Chugh, Rohit; Skube, Steven J; Majumder, Kaustav; Banerjee, Sulagna; Sangwan, Veena; Li, Lihua; Dawra, Rajinder; Subramanian, Subbaya; Saluja, Ashok; Dudeja, Vikas

2015-06-01

Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude

Implications of microbiota and bile acid in liver injury and regeneration

PubMed Central

Liu, Hui-Xin; Keane, Ryan; Sheng, Lili; Wan, Yu-Jui Yvonne

2015-01-01

Summary Studies examining the mechanisms by which the liver injures and regenerates usually focus on factors and pathways within the liver, neglecting the signaling derived from the gut-liver axis. The intestinal content is rich in microorganisms as well as metabolites generated from both the host and colonizing bacteria. Via the gut-liver axis, this complex “soup” exerts an immense impact on liver integrity and function. This review article summarizes data published in the past 30 years that have demonstrated the signaling derived from the gut-liver axis in relation to liver injury and regeneration. Despite many correlative findings, the intricate networks of pathways involved along with a scarcity of mechanistic data urgently require nutrigenomic, metabolomics, and microbiota profiling approaches to provide a deep understanding of the interplay between nutrition, bacteria, and host response. Such knowledge would better elucidate the molecular mechanisms that link microbiota alteration to host physiological response and vice-versa. PMID:26256437

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-07-01

Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Imaging Plasmodium Immunobiology in Liver, Brain, and Lung

PubMed Central

Frevert, Ute; Nacer, Adéla; Cabrera, Mynthia; Movila, Alexandru; Leberl, Maike

2013-01-01

Plasmodium falciparum malaria is responsible for the deaths of over half a million African children annually. Until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2D monocultures or entirely artificial surfaces. Due to extremely low parasite densities, the liver was considered a black box in terms of Plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. Further, nothing was known about the behavior of blood stage parasites in organs such as brain where clinical signs manifest and the ensuing immune response of the host that may ultimately result in a fatal outcome. The advent of fluorescent parasites, advances in imaging technology, and availability of an ever-increasing number of cellular and molecular probes have helped illuminate many steps along the pathogenetic cascade of this deadly tropical parasite. PMID:24076429

Predictors of deterioration of lung function in Polish children with cystic fibrosis.

PubMed

Olszowiec-Chlebna, Małgorzata; Koniarek-Maniecka, Agnieszka; Stelmach, Włodzimierz; Smejda, Katarzyna; Jerzyńska, Joanna; Majak, Paweł; Białas, Monika; Stelmach, Iwona

2016-04-01

Severity of lung disease varies in patients with the same CFTR genotype. It suggests that other factors affect the severity of cystic fibrosis (CF). The aim of the study was to identify risk factors that determine lung function decline in Polish cystic fibrosis children. The follow-up time was no less than 5 years of respiratory status observation based on the forced expiratory volume in 1 s value (FEV1). The socio-economic data, perinatal interview, presence of meconium ileus (MI), time of CF diagnosis, initiation of tobramycin inhalation solution (TIS), pancreatic function, sensitization to Aspergillus fumigatus, presence of impaired glucose tolerance (IGT) or diabetes mellitus, chronic bacterial colonization and number of exacerbations and hospitalizations were assessed. The mean age of 61 included children was 13.3 ±7.6 years. Delta F508 homozygosity was detected in 45.9%, 44.3% were delta F508 heterozygous, and 9.8% had other genotypes. FEV1 decline was observed among 20% of patients; the rest of the patients presented stable values of FEV1 during at least 5 years of observation. The most significant predictors related to the decline of FEV1 were presentation of MI (p = 0.0344), IGT (p = 0.0227), number of exacerbations (p = 0.0288), and early Pseudomonas aeruginosa (PA) chronic colonization (p = 0.0165) followed by late TIS initiation after the first detection of PA (p=0.0071). Neither time of diagnosis nor type of CFTR mutation was statistically significant as a predictor of lung deterioration. The presence of MI, IGT, chronic PA colonization, and number of exacerbations are risk factors for lung function deterioration.

PROMOTION OF TRIHALOMETHANE-INDUCED COLON, ABERRANT CRYPT FOCI (ACF) BY A HIGH FAT DIET

EPA Science Inventory

Abstract:

Bromodichloromethane (BOCM) and tribromomethane (TBM) enhanced neoplasia in the large intestine of rats when given by corn oil gavage; BOCM in the drinking water to male rats did not induce colon tumors, but did increase liver tumors. However, TBM and a mixture o...

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.

PubMed

Rimkus, C; Martini, M; Friederichs, J; Rosenberg, R; Doll, D; Siewert, J R; Holzmann, B; Janssen, K P

2006-11-20

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer.

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer

PubMed Central

Rimkus, C; Martini, M; Friederichs, J; Rosenberg, R; Doll, D; Siewert, J R; Holzmann, B; Janssen, K P

2006-01-01

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein–protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer. PMID:17088907

Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK

PubMed Central

Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun; Bode, Ann M.; Lee, Hyo-Jeong; Heo, Yong-Seok; Boardman, Lisa; Limburg, Paul; Lee, Hyong Joo; Dong, Zigang

2011-01-01

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation. PMID:21317303

Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK.

PubMed

Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun; Bode, Ann M; Lee, Hyo-Jeong; Heo, Yong-Seok; Boardman, Lisa; Limburg, Paul; Lee, Hyong Joo; Dong, Zigang

2011-06-01

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.

[A case of fulminant hepatic failure secondary to hepatic metastasis of small cell lung carcinoma].

PubMed

Hwang, Young Tae; Shin, Jung Woo; Lee, Jun Ho; Hwang, Dae Sung; Eum, Jun Bum; Choi, Hye Jeong; Park, Neung Hwa

2007-12-01

Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma.

Time-dependence of lung injury in mice acutely exposed to cylindrospermopsin.

PubMed

Oliveira, V R; Carvalho, G M C; Avila, M B; Soares, R M; Azevedo, S M F O; Ferreira, T S; Valença, S S; Faffe, D S; Zin, Walter Araujo

2012-10-01

Cylindrospermopsin is a cyanobacterial toxin of increasing environmental importance, as it can lead to disease if orally or intravenously absorbed. However, its in vivo lung impairment has not been documented. Thus, we aimed at verifying whether cylindrospermopsin can induce lung injury and establish its putative dependence on the time elapsed since exposure. BALB/c mice were intratracheally injected with either saline (NaCl 0.9%, 50 μL, SAL group, n = 12) or a sublethal dose (70 μg/kg) of semi-purified extract of cylindrospermopsin (CYN groups, n = 52). Lung mechanics, histological and biochemical analyses, and cylindrospermopsin presence in lungs and liver were determined in independent groups at 2, 8, 24, 48, and 96 h after cylindrospermopsin instillation. There was a significant increase in static elastance at 24 and 48 h after exposure to cylindrospermopsin, while viscoelastic component of elastance and viscoelastic pressure rose at 48 h. Alveolar collapse augmented in CYN groups at 8 h. A significant increase in polymorphonuclear influx into lung parenchyma, as well as a higher myeloperoxidase activity started off at 24 h. Exposure to cylindrospermopsin increased lipid peroxidation and superoxide dismutase activity and reduced catalase activity in CYN groups. The toxin was detected in lungs and liver of all CYN mice. In conclusion, cylindrospermopsin exposure impaired lung mechanics, which was preceded by lung parenchyma inflammation and oxidative stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

Magnetic-Targeted Doxorubicin in Treating Patients With Cancer Metastatic to the Liver

ClinicalTrials.gov

2005-06-23

Metastases, Neoplasm; Colorectal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Breast Neoplasms; Melanoma; Sarcoma; Gastrointestinal Neoplasms; Lung Neoplasms; Liver Neoplasms; Cholangiocarcinoma

Modeling liver physiology: combining fractals, imaging and animation.

PubMed

Lin, Debbie W; Johnson, Scott; Hunt, C Anthony

2004-01-01

Physiological modeling of vascular and microvascular networks in several key human organ systems is critical for a deeper understanding of pharmacology and the effect of pharmacotherapies on disease. Like the lung and the kidney, the morphology of its vascular and microvascular system plays a major role in its functional capability. To understand liver function in absorption and metabolism of food and drugs, one must examine the morphology and physiology at both higher and lower level liver function. We have developed validated virtualized dynamic three dimensional (3D) models of liver secondary units and primary units by combining a number of different methods: three-dimensional rendering, fractals, and animation. We have simulated particle dynamics in the liver secondary unit. The resulting models are suitable for use in helping researchers easily visualize and gain intuition on results of in silico liver experiments.

High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

PubMed

Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

A ten-year study of penetrating injuries of the colon.

PubMed

Adesanya, Adedoyin A; Ekanem, Ekanem E

2004-12-01

Colon injury has been associated with a high risk of septic complications and mortality. We prospectively studied the pattern, management, outcome, and prognostic factors in patients who sustained penetrating colon injuries. Sixty patients who presented to our hospital with penetrating colon injuries over a ten-year period (1992 to 2001) were studied. Colon wounds were caused by gunshots in 55 (91.7 percent) patients and knife stabs in 5 (8.3 percent). There was a delay of more than 12 hours before laparotomy in 30 (50 percent) patients. Moderate or major fecal contamination of the peritoneal cavity occurred in 58 (96.7 percent) patients. The average penetrating abdominal trauma index score was 25.9 and 20 (33.3 percent) patients sustained Flint Grade 3 colon injury. Associated intra-abdominal injuries occurred in the small bowel (73.3 percent), liver (25 percent), stomach (23.3 percent), and mesentery (16.7 percent). Right colon wounds (35) were managed by primary repair in 24 (68.6 percent) patients and proximal diverting colostomy in 11 (31.4 percent), whereas left colon wounds (25) were managed by diverting colostomy in 22 (88.0 percent) patients and primary repair in 3 (12.0 percent) patients. Common complications included wound infection (56.7 percent), septicemia (31.7 percent), and enterocutaneous fistula (16.7 percent). The overall mortality rate was 33.3 percent and colon injury-related mortality was 21.7 percent. Presence of destructive colon injury was associated with a greater than fourfold increased incidence of death. Other significant risk factors included shock on admission, major fecal contamination, duration of operation more than four hours, penetrating abdominal trauma index score >25, and more than two postoperative complications. There was no difference in outcome between patients who had primary repair and those undergoing diverting colostomy. Colostomy closure-related morbidity was 21 percent and mortality was 5.3 percent. A more liberal

[A case of a perivascular epithelioid cell tumor mimicking colon cancer].

PubMed

Cho, Young Whan; Kim, Kyung Jo; Ye, Byong Duk; Byeon, Jeong Sik; Myung, Seung Jae; Yang, Suk Kyun; Kim, Jin Ho

2012-12-01

Perivascular epithelioid cell tumor (PEComa) is extremely rare, which originated from mesenchymal cells in the intestine, and composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. We report here on a case of PEComa in the sigmoid colon. A 62-year-old woman presented with hematochzia 10 days ago. Her abdominal computed tomography scan showed a 5 cm sized intraluminal fungating heterogeneously enhanced, high density mass, which infiltrated pericolic tissue surrounding the sigmoid colon. Colonoscopy showed a purple colored polypoid mass with lobulating contour in the sigmoid colon. She underwent laparoscopic anterior resection. On the histologic examination, the tumor consisted of polygonal epithelioid cells with sheet-like growth of nests, which looked like alveolar tissues in lung. The tumor cells were strongly positive stained with human melanoma black-45 (HMB-45). Pathologic examination was compatible with PEComa. Sixteen months after surgery, she did well without tumor recurrence after surgery. We review the literatures concerning PEComa of the intestine focusing on endoscopic findings.

Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer

PubMed Central

YOSHIMOTO, KATSUHIRO; TAJIMA, HIDEHIRO; OHTA, TETSUO; OKAMOTO, KOICHI; SAKAI, SEISHO; KINOSHITA, JUN; FURUKAWA, HIROYUKI; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAMURA, KEISHI; OYAMA, KATSUNOBU; INOKUCHI, MASAFUMI; NAKAGAWARA, HISATOSHI; ITOH, HIROSHI; FUJITA, HIDETO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; WAKAYAMA, TOMOHIKO; ISEKI, SHOICHI; SHIMIZU, KOICHI

2012-01-01

Several recent studies have reported that selectins are produced during ischemia-reperfusion injury, and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis. PMID:22766603

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

ClinicalTrials.gov

2018-02-12

Uterine Sarcoma; Stage IV Bladder Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Urethral Cancer; Stage IVA Cervical Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Cervical Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Stage IVB Uterine Sarcoma; Ureter Cancer; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage IIIB Lung Carcinoma

Liver, kidney, and thoracic organ transplantation under FK 506.

PubMed Central

Todo, S; Fung, J J; Starzl, T E; Tzakis, A; Demetris, A J; Kormos, R; Jain, A; Alessiani, M; Takaya, S; Shapiro, R

1990-01-01

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index. PMID:1697743

Cyto-adherence of Mycoplasma mycoides subsp. mycoides to bovine lung epithelial cells.

PubMed

Aye, Racheal; Mwirigi, Martin Kiogora; Frey, Joachim; Pilo, Paola; Jores, Joerg; Naessens, Jan

2015-02-07

Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a respiratory disease of cattle, whereas the closely related Mycoplasma mycoides subsp. capri (Mmc) is a goat pathogen. Cyto-adherence is a crucial step in host colonization by mycoplasmas and subsequent pathogenesis. The aim of this study was to investigate the interactions between Mmm and mammalian host cells by establishing a cyto-adherence flow cytometric assay and comparing tissue and species specificity of Mmm and Mmc strains. There were little significant differences in the adherence patterns of eight different Mmm strains to adult bovine lung epithelial cells. However, there was statistically significant variation in binding to different host cells types. Highest binding was observed with lung epithelial cells, intermediate binding with endothelial cells and very low binding with fibroblasts, suggesting the presence of effective adherence of Mmm on cells lining the airways of the lung, which is the target organ for this pathogen, possibly by high expression of a specific receptor. However, binding to bovine fetal lung epithelial cells was comparably low; suggesting that the lack of severe pulmonary disease seen in many infected young calves can be explained by reduced expression of a specific receptor. Mmm bound with high efficiency to adult bovine lung cells and less efficiently to calves or goat lung cells. The data show that cyto-adherence of Mmm is species- and tissue- specific confirming its role in colonization of the target host and subsequent infection and development of CBPP.

Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research.

PubMed

Wang, Yang; Weng, Tingting; Gou, Deming; Chen, Zhongming; Chintagari, Narendranath Reddy; Liu, Lin

2007-01-24

An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis. The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.

Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil.

PubMed

de Souza Carraro, Danila; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Iuamoto, Leandro Ryuchi; Braga, Karina Andrighetti de Oliveira; Oliveira, Lea Campos de; Sabino, Ester Cerdeira; Rossi, Flavia; Pêgo-Fernandes, Paulo Manuel

2018-03-12

To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

PubMed

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-02-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. © 2014 John Wiley & Sons Ltd.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

PubMed Central

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-01-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

PubMed

Helmi, Mohamed; Love, Robert B; Welter, Debbie; Cornwell, Richard D; Meyer, Keith C

2003-03-01

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. A university hospital. Lung transplant recipients with CF or other indications for transplantation. None. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect

Disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis in a lung transplant recipient.

PubMed

Scherer, Mirela; Fieguth, Hans-Gerd; Aybek, Tayfun; Ujvari, Zsolt; Moritz, Anton; Wimmer-Greinecker, Gerhard

2005-12-01

Aspergillus infection is a known complication of lung transplantation and remains associated with high mortality rates. The manifestation of the infection varies from simple colonization of the lung to disseminated complicated infections. Early Aspergillus infection has been rarely observed in a small number of lung transplant recipients; most cases occur during the late post-operative period. The pulmonary involvement has often been described as the first clinical localization of the disease. Although other various forms of Aspergillus infection are not uncommonly encountered after lung transplantation, Aspergillus mitral valve endocarditis is rare. We present a case of disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis having developed 78 days after double-lung transplantation for cystic fibrosis.

Induction of Apoptosis of 2,4′,6-Trihydroxybenzophenone in HT-29 Colon Carcinoma Cell Line

PubMed Central

Lay, Ma Ma; Karsani, Saiful Anuar

2014-01-01

2,4′,6-Trihydroxy-4-methoxybenzophenone was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl. fruits. It was found to inhibit cell proliferation in HT-29 human colon carcinoma cell line but caused little damage to WRL-68 normal human liver and MRC-5 normal human fibroblast lung cell lines. The compound was found to sharply affect the viability of HT-29 cells in a dose- and time-dependent manner. HT-29 cells treated with the compound showed morphological changes under microscopic examination such as cell shrinkage, membrane blebbing, DNA fragmentation, and the occurrence of apoptotic nuclei. The percentage of early apoptotic, late apoptotic, and dead or necrotic cells was determined by flow cytometry using annexin V-FTIC/PI staining. In addition, flow cytometry showed that, when the HT-29 cells were treated with 115 µM of the compound, it resulted in G0/G1 phase arrest in a time-dependent manner. Western blot revealed an upregulation of PUMA, Bak, Bcl-2, and Mcl-1 proteins suggesting that the compound induced apoptosis in HT-29 cells by regulating these proteins. PMID:24579081

Cancer Chemoprevention by Citrus Pulp and Juices Containing High Amounts of β-Cryptoxanthin and Hesperidin

PubMed Central

Tanaka, Takuji; Tanaka, Takahiro; Tanaka, Mayu; Kuno, Toshiya

2012-01-01

β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs. PMID:22174562

Diversity in the association between occupation and lung cancer among black and white men.

PubMed

Swanson, G M; Lin, C S; Burns, P B

1993-01-01

A population-based case comparison study of incident lung cancer and occupational risk factors was conducted in the tricounty Detroit metropolitan area. Nearly 6000 lung cancer cases and a comparison group of 3600 colon cancer cases were interviewed. This report includes 3792 white and black male lung cancer cases and 1966 black and white colon cancer referents. Cigarette smoking, age at diagnosis, and lifetime work history were assessed to determine the relationship between length of employment in specific occupations and industries and lung cancer. Diverse patterns of association between work history and lung cancer were observed for black and white men. Significant associations were seen between lung cancer and increasing length of employment in the following occupations: for white men, concrete and terrazzo finishers, grinding machine operators, heat treating machine operators, miscellaneous machine operators, truck drivers, driver sales, and laborers; for black men, farm workers, automobile mechanics, painting machine operators, furnace operators, and garbage collectors; for both black and white men, farmers, slicing and cutting machine operators, and garbage collectors. Distinct patterns for black and white men also were observed for length of employment by industry. This study clearly demonstrates the need to include black men in studies of occupational cancer etiology and to evaluate black and white men separately. It also indicates the necessity for cigarette smoking history to accurately assess workplace cancer risks. We propose guidelines for incorporating the use of biomarkers into further studies of occupational cancer epidemiology.

Muscle metastasis from non-small cell lung cancer: two cases and literature review.

PubMed

Tezcan, Y; Koc, M

2014-08-01

Non-small cell lung cancers (NSCLC) is the most commonly observed group among lung cancers. Adenocancers are histopathologically more common. Males are more affected than females, an effect which is directly related to smoking. They generally cause distant haematogenous and lymphatic metastasis. Distant haematogenous metastases are often seen in contralateral lung, brain, bone, adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases are more frequently affected compared to female cases. NSCLC cases with muscle metastasis are at the same time accompanied by distant organ metastases such as bone, brain, and liver. All treatment approaches are considered to be palliative in these cases, which are symptomatologically quite severe. In the present study, we presented the rarely observed cases of two male patients with muscle metastasis from NSCLC together with the related literature.

Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

PubMed

Byrd, Wyatt; Boedeker, Edgar C

2013-03-15

Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

Pharmacological considerations for azole antifungal drug management in cystic fibrosis lung transplant patients.

PubMed

Billaud, Eliane M; Guillemain, Romain; Berge, Maud; Amrein, Catherine; Lefeuvre, Sandrine; Louët, Agnès Lillo-Le; Boussaud, Véronique; Chevalier, Patrick

2010-11-01

This paper aims to present our experience in the pharmacological approach of the management of azole antifungal drugs in cystic fibrosis lung transplant patients. Cystic fibrosis (CF) lung transplantation is associated with multi-factorial care management, because of immunosuppressive requirements, risk of infections, frequency of gastro-oesophageal reflux disease, hepatic alterations and CF pharmacokinetics (PK) specificities that result in important PK variability. CF is associated with frequent colonization of the airways by filamentous fungi, especially by Aspergillus species. Today the antifungal therapeutic arsenal offers several possibilities for long-term oral therapy including azole drugs (itraconazole, voriconazole and posaconazole). Therefore, nephrotoxic amphotericin B should be avoided. The liver is important in the pharmacological profile of azole drugs, due to metabolic elimination, hepatotoxicity and PK drug-drug interaction (DDI) involving CYP3A4 metabolic inhibition. Targets for such DDI are numerous, but immunosuppressive drugs are of major concern, justifying combined therapeutic drug monitoring (TDM) of both azoles (inhibitors) and immunosuppressants (targets) on an individualized patient basis to adjust the coprescription quantitatively. The risk of long under-dosed periods, frequently addressed in this population, could justify, on a PK basis, the need for combination with an exclusive parenteral antifungal while waiting for azole relevant drug level. High PK variability, the risk of low exposure, therapeutic issues and DDI management in this complex underlying disease justify close monitoring with systematic combined TDM of azole and immunosuppressants, in case of coprescription.

Immuno-proteomic discovery of tumor tissue autoantigens identifies olfactomedin 4, CD11b, and integrin alpha-2 as markers of colorectal cancer with liver metastases.

PubMed

Yang, Qian; Bavi, Prashant; Wang, Julia Y; Roehrl, Michael H

2017-09-25

Late-stage colorectal cancer with liver metastasis is common and affords poor prognosis, yet there is a dearth of reliable biomarkers. Cancer is often characterized by an increase in serologic autoantibodies. Hence, we embarked on an immuno-proteomic strategy by using autoantibodies to discover antigens in tumor tissue as potential cancer markers. Matched sets of tissues from primary colon cancer, liver metastases, and adjacent benign tissues were obtained from colon cancer patients. Tissue proteins were extracted, and autoantigens were uncovered by immunoblotting with autoantibodies and sequenced by mass spectrometry. Informatics analyses identified 48 proteins that were found in tumor only but were absent in normal tissue. Five of these were reproducibly found in two independent experiments, including olfactomedin 4 (OLFM4), CD11b, integrin α2 (ITGA2), periostin, and thrombospondin-2. Further confirmation with tissue from 43 patients by Western blotting, immunohistochemistry, and tissue microarray deemed OLFM4, CD11b, and ITGA2 to be significantly overexpressed in both primary colon tumors and liver metastases. These tumor tissue autoantigens may serve as promising markers for developing differential diagnostics and immunotherapies for colorectal cancers, in particular, those with tendency to progress to liver metastases. Late-stage colorectal cancer with liver metastasis is common and affords poor prognosis, yet there is a dearth of reliable biomarkers. Cancer is often characterized by an increase in serologic autoantibodies. Cancer tissue immunogens - antigens capable of inducing specific antibody production in patients - are promising targets for development of precision diagnostics and immunotherapies. In our manuscript, we describe on an immuno-proteomic strategy by using autoantibodies to discover antigens in tumor tissue as potential cancer markers. Matched sets of tissues from primary colon cancer, liver metastases, and adjacent benign tissues were

Cystic fibrosis lung transplantation.

PubMed

Braun, Andrew T; Merlo, Christian A

2011-11-01

This review summarizes recently published investigations on issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically focus on indications and candidate selection as well as infectious and noninfectious issues specific to CF lung transplant recipients. Recent studies have focused on candidate adequacy in high-risk CF patients. We review the current literature on individuals who develop respiratory failure requiring mechanical ventilation and those patients with a pretransplant diagnosis of pulmonary hypertension. Furthermore, the management of peri-operative infectious issues is reviewed including recurrent infections with multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF-specific issues addressed include common comorbidities such as CF-related diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism. Lung transplantation is a limited, but potentially life-saving therapeutic option for patients with CF. Optimal candidate selection and awareness of CF-specific issues in the pretransplant and posttransplant setting may lead to better long-term outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment

PubMed Central

Håkansson, Åsa; Bränning, Camilla; Molin, Göran; Adawi, Diya; Hagslätt, Marie-Louise; Jeppsson, Bengt; Nyman, Margareta; Ahrné, Siv

2012-01-01

Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated. Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed. Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation

Cancer incidence among alcoholic liver disease patients in Finland: A retrospective registry study during years 1996-2013.

PubMed

Sahlman, Perttu; Nissinen, Markku; Pukkala, Eero; Färkkilä, Martti

2016-06-01

Both alcohol abuse and liver cirrhosis are known risk factors for various cancers. This article was aimed to assess the long-term risk of malignancies among patients with severe alcoholic liver disease (ALD), i.e., alcoholic liver cirrhosis and alcoholic hepatitis. A cohort of 8,796 male and 3,077 female ALD patients from 1996 to 2012 was identified from the Finnish National Hospital Discharge Register. This nationwide cohort was combined with the data from the Finnish Cancer Registry for incidence of malignancies during the years 1996-2013. The cancer cases diagnosed were compared with the number of cancers in the general population. The number of malignancies in our cohort was 1,052 vs. 368 expected. There was statistically significant excess of cancers of the liver, (standardized incidence ratio [SIR] 59.20; 95% CI 53.11-65.61), pancreas (SIR 3.71; 95% CI 2.72-4.94), pharynx (SIR 9.25; 95% CI 6.05-13.56), mouth (SIR 8.31; 95% CI 4.84-13,29), oesophagus (SIR 7.92; 95% CI 5.49-11.07), tongue (SIR 7,21; 95% CI 3.60-12.89), larynx (SIR 5.20; 95% CI 2.77-8.89), lung (SIR 2.77; 95% CI 2.27-3.32), stomach (SIR 2.76; 95% CI 1.79-4.07), kidney (SIR 2.69; 95% CI 1.84-3.79) and colon (SIR 2.33; 95% CI 1.70-3.11). There was no decreased risk of any cancer among ALD patients. Severe ALD is associated with markedly increased risk of malignancies. The risk is especially high for hepatocellular carcinoma, but also significantly increased for cancers of the upper aerodigestive tract, pancreas and kidneys, and warrants cancer surveillance in selected cases. © 2016 UICC.

Strongylus equinus: development and pathological effects in the equine host.

PubMed Central

McCraw, B M; Slocombe, J O

1985-01-01

The development and pathological effects of Strongylus equinus were studied in 17 pony foals and one horse foal raised in isolation and examined at necropsy from seven days to 40 wk postinfection (PI). Following inoculation of 15000 +/- 6% or 16000 +/- 6% infective larvae by stomach tube foals were monitored for clinical signs and selected blood changes. Larvae penetrated the wall of the ileum, cecum and colon. The molt to the fourth stage occurred mostly in the wall of the ventral colon before 2 wk PI and larvae attained the liver mainly via the peritoneal cavity as early as eight days PI and persisted in the liver until 17 wk PI. Following active migration within the liver, invasion of the pancreas was accomplished at least by 7 wk PI with maximum numbers at 17 wk. The fourth molt occurred about 15 wk PI and preadults were present in the wall of the ventral colon at 30 wk PI and in the lumen of the colon at 40 wk. Strongylus equinus tends to wander retroperitoneally to the flanks, perirenal fat, diaphragm, omentum and occasionally to the lungs. Between 1 and 4 wk PI small raised hemorrhagic areas were present on the serosa of the ileum and colon. Small white foci on the surface of the liver at 1 wk PI were followed by tortuous tracks 3 wk later. Pathological changes in the pancreas were evident at three months PI and more severe by four months. Granulomas containing larvae were common in the flanks, diaphragm, omentum and occasionally beneath the pleura of the lungs. Clinical signs were correlated with invasion of the pancreas, the fourth molt, maximum globulin values and high eosinophil counts. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. PMID:4075237

CureOne Registry: Advanced Malignancy or Myelodysplasia, Tested by Standard Sequencing and Treated by Physician Choice

ClinicalTrials.gov

2017-10-02

Neoplasms; Lung Neoplasms; Colon Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Prostate Neoplasms; Kidney Neoplasms; Liver Neoplasms; Rectal Neoplasms; Hematologic Neoplasms; Multiple Myeloma; Myelodysplastic Syndromes; Ovarian Neoplasms; Bladder Neoplasms; Testicular Neoplasms; Endometrial Neoplasms; Brain Neoplasms; Biliary Tract Neoplasms; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Skin Neoplasms; Melanoma; Gastric Neoplasms; Anal Neoplasms; Sarcoma

[Cancer treatment situation in Japan with regard to the type of medical facility using medical claim data of Health Insurance Societies].

PubMed

Tanaka, Hirokazu; Nakamura, Fumiaki; Higashi, Takahiro; Kobayashi, Yasuki

2015-01-01

Analyzing the cancer treatment situation in Japan is an important public health issue, especially because of increasing crude cancer morbidity in a rapidly aging society. This study aimed to examine where cancer patients received treatment, with special attention to designated regional cancer hospitals, and the treatment modality they received. Using health insurance claim data (1,064,875 subjects on December 2011) managed by the Japan Medical Data Center, we included patients that received treatments for stomach, colon, liver, lung, or breast cancer, the most common cancers in Japan, between 2005 and 2011. We divided the medical facilities where they were treated into five groups: prefectural designated regional cancer hospitals, local designated regional cancer hospitals, large/medium hospitals (≥100 beds), small hospitals (20-99 beds), and clinics (0-19 beds). We calculated the percentage of patients treated at each type of medical facility with different treatment modalities. The study included 2,901 patients. In total, 43.9% patients were treated at designated regional cancer hospitals (prefectural or local). This percentage was the highest for lung cancer (60.0%) and the lowest for colon cancer (31.3%). Surgeries for liver cancer (67.6%) and lung cancer (61.9%) were performed more at designated regional cancer hospitals (prefectural or local) than surgeries for stomach cancer (45.5%), colon cancer (40.1%), and breast cancer (49.8%). Some procedures were performed at small hospitals or clinics (surgery for stomach cancer [9.4%], surgery for breast cancer [9.3%], endoscopic procedures for stomach cancer [14.1%] and colon cancer [40.6%], and chemotherapy for breast cancer [11.4%]). Colon and breast cancer patients treated at prefectural designated regional cancer hospitals or clinics were younger than those treated at other types of facilities. The distribution of facilities at which cancer patients received treatment differed significantly according to cancer

Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillams, Alice, E-mail: alliesorting@gmail.com; Khan, Zahid; Osborn, Peter

2013-06-15

Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, andmore » factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.« less

Colon cancer

MedlinePlus

Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... In the United States, colorectal cancer is one of the leading ... to cancer. Early diagnosis can often lead to a complete cure. ...

GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis

PubMed Central

Andersen, L; Hasenöhrl, C; Feuersinger, D; Stančić, A; Fauland, A; Magnes, C; El‐Heliebi, A; Lax, S; Uranitsch, S; Haybaeck, J; Heinemann, A

2015-01-01

Background and Purpose Tumour cell migration and adhesion constitute essential features of metastasis. G‐protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells. Experimental Approach Adhesion and migration assays using the highly metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis were performed. The GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells. Key Results HCT116 cells showed a significant decrease in adhesion to endothelial cells and in migration after blockade with CID16020046 or cannabidiol. The inhibitory effects of CID16020046 or cannabidiol were averted by GPR55 siRNA knock down in cancer cells. The integrity of endothelial cell monolayers was increased after pretreatment of HCT116 cells with the antagonists or after GPR55 siRNA knockdown while pretreatment with lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, decreased integrity of the monolayers. LPI also induced migration in GPR55 overexpressing HCT116 cells that was blocked by GPR55 antagonists. In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol. Increased levels of LPI (18:0) were found in colon cancer patients when compared with healthy individuals. Conclusions and Implications GPR55 is involved in the migratory behaviour of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis. © 2015 The British Pharmacological Society PMID:26436760

[Investigation of Pneumocystis jirovecii pneumonia and colonization in iatrogenically immunosuppressed and immunocompetent patients].

PubMed

Özkoç, Soykan; Bayram Delibaş, Songül

2015-04-01

Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be detected in healthy individuals and in patients with various underlying lung diseases. The aim of this study was to evaluate the immunocompetent and iatrogenically immunosuppressed patients in terms of PCP and P.jirovecii colonization. A total of 92 patients (66 male, 26 female; age range: 18-93 years, median: 58.5) who underwent bronchoscopy due to various pulmonary symptoms between January 2011-April 2014, were included in the study. Of these patients, 65 were under immunosuppressive therapy (38 were treated with anti-cancer drugs, 15 with anti-rejection/immunomodulatory drugs and 12 with corticosteroids), while 27 were immunocompetent. Bronchoalveolar lavage (BAL) fluids were evaluated for the presence of P.jirovecii mitochondrial gene coding ribosomal large subunit (mtLSUrRNA) with nested PCR (nPCR) method. All of the samples were also examined by Giemsa and Gomori's methenamine silver (GMG) staining methods. P.jirovecii DNA was detected in 31 (33.7%) out of 92 BAL samples by nPCR. Although six immunosuppressed patients were positive in the first round of amplification, 26 of 65 (40%) immunosuppressed and five of 27 (18.5%) immunocompetent patients were positive with nPCR. P.jirovecii cysts and trophozoites were detected in only five (16.1%) of the 31 nPCR positive samples. The probability of being immunosuppressive among nPCR positive cases was statistically higher than nPCR negative cases (χ²= 3.940; p= 0.047). This difference was more significant in organ transplant recipients and patients under anti-rejection/immunomodulatory treatment (χ²= 6.715, p= 0.01; χ²= 5.550, p= 0.018, respectively). When clinical, laboratory and radiological findings of nPCR positive patients were considered, five patients (2 kidney transplant, 1 bone marrow transplant, 1 interstitial lung disease and 1 lung

Perceived stigmatization and its impact on quality of life - results from a large register-based study including breast, colon, prostate and lung cancer patients.

PubMed

Ernst, J; Mehnert, A; Dietz, A; Hornemann, B; Esser, P

2017-11-09

To date, research on stigmatization among cancer patients and related psychosocial consequences has been scarce and mostly based on small and highly selected samples. We investigated stigmatization and its impact on quality of life among a large sample including four major tumor entities. We assessed 858 patients with breast, colon, lung or prostate cancer from two cancer registries. Stigmatization and quality of life (QoL) was assessed with the Social Impact Scale (SIS-D) and the EORTC Quality of Life Questionnaire (European Organization for Research and Treatment of Cancer), respectively. Group effects were analyzed via analyses of variance, relationships were investigated via Pearson's r and stepwise regression analyses. The mean age was 60.7 years, 54% were male. Across cancer sites, the dimensions of stigmatization (isolation, social rejection, financial insecurity and internalized shame) were in the lower and middle range, with the highest values found for isolation. Stigmatization was lowest among prostate cancer patients. Stigmatization predicted all five areas of QoL among breast cancer patients (p < .05), but only affected emotional functioning (p < .01) among lung cancer patients. We found an inverse relationship between perceived cancer-related stigmatization and various dimensions of QoL, with variation between cancer sites. Breast cancer patients should be focused in individual therapies regarding the negative consequences accompanied by perceived stigmatization.

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo

PubMed Central

Ge, Xiangting; Feng, Zhiguo; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Xu, Fengli; Fu, Lili; Shan, Xiaoou; Dai, Yuanrong; Zhang, Yali; Liang, Guang

2016-01-01

Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases. PMID:27390516

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo.

PubMed

Ge, Xiangting; Feng, Zhiguo; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Xu, Fengli; Fu, Lili; Shan, Xiaoou; Dai, Yuanrong; Zhang, Yali; Liang, Guang

2016-01-01

Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

Impact of organ transplantation in heart, lung and liver recipients: assessment of positive life changes.

PubMed

Anand-Kumar, Vinayak; Kung, Mary; Painter, Liz; Broadbent, Elizabeth

2014-01-01

The majority of psychological studies with organ transplant recipients have examined negative psychological effects. This study aimed to further investigate the positive effects of organ transplantation and to construct a specific measurement instrument. The initial pool of 14 items for the Positive Effects of Transplant Scale (PETS) was derived from organ recipient interviews. A cross-sectional postal study included 87 heart, 46 lung and 193 liver transplant recipients. The PETS was subjected to principal components analysis (PCA) using varimax rotation, and associations with other measures investigated. PETS and an open-ended item about positive effects. Coding of the open-ended item revealed that the majority of recipients attributed positive life changes to the transplant experience. PCA of the PETS indicated three factors that accounted for 58.82% of the variance. The 12-item questionnaire assesses improvements in: (1) life philosophy, (2) gratitude and (3) health. The total PETS scores exhibited adequate internal consistency and validity. Most transplant patients report positive psychological effects, which suggests this may be an understudied area. The initial development of an assessment tool provides researchers and clinicians a way to assess the degree and nature of these life changes.

Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

PubMed Central

Rom, William N.; Weiden, Michael D.

2014-01-01

Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus–infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. PMID:24460444

The impact of primary tumour location in patients undergoing hepatic resection for colorectal liver metastasis.

PubMed

Wang, Kun; Xu, Da; Yan, Xiao-Luan; Poston, Graeme; Xing, Bao-Cai

2018-06-01

Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015. Right-sided (RS) tumours include tumours located in the cecum, ascending colon, and transverse colon, and left-sided (LS) tumours include those located in the splenic flexure, descending colon, sigmoid colon, and rectum. Both overall survival (OS) and disease-free survival (DFS) were similar between patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5-year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis showed that the RAS mutation on the LS and RS tumours have different prognostic impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable analysis showed that RAS mutant is an independent factor influencing OS in patients with LS primary tumour only. The site of the primary tumour has no significant impact on the long-term survival in patients with CRLM undergoing radical surgery. However, prognostic value of RAS status differs depending on the site of the primary tumour. Copyright © 2018. Published by Elsevier Ltd.

Dynamic morphological examination and evaluation of biological characteristics of a multinodular liver cancer model in mice.

PubMed

Li, Yan-Ru; Wang, Jin-Rui; Zhang, Hai-Ying; Wu, Xiao-Fei; Li, Sheng-Nan; Wang, Lin; Wang, Xue-Yao

2014-04-01

Compared with single nodular liver cancer, the prominent biological characteristics of multinodular liver cancer include rapid progression and short survival. Here, we developed a multinodular liver cancer model in mice and assessed the biological characteristics of the resulting neoplasms. H22 hepatoma cells at a dose of 2 × 10(5)/mouse, suspended in 1.6 mL, 0.8 mL, or 200 µL saline were injected via the tail vein of BALB/c mice at a velocity of 200 µL per second. The mice were sacrificed at different time points after injection. And at the time of death the liver, lungs, spleen, kidneys and heart were removed for morphological study. The biological characteristics of the tumor nodules were evaluated by immunohistochemistry. In the mice treated with a large volume injection of H22 cells, by day 7, there was a 100% occurrence of multinodular tumors in the livers, determined by histology. At the time of death, there were 100%, 100%, 37.5% and 37.5% occurrences of tumors in the lungs, kidneys, spleen and heart, respectively. The neoplastic cells in the liver nodules showed pleomorphism, and exhibited high expression of proliferating cell nuclear antigen (PCNA), c-myc, vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2). In mice treated with a small or medium volume injection, no tumor cells were identified in the livers, spleen, kidneys or heart at any of the examined time points. By day 7 and at the time of death, there was a 100% occurrence of tumor in the lungs. A multinodular liver cancer model in mice was achieved using a large volume injection of H22 cells.

Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients.

PubMed

Prigent, Gwénolé; Aït-Ammar, Nawel; Levesque, Eric; Fekkar, Arnaud; Costa, Jean-Marc; El Anbassi, Sarra; Foulet, Françoise; Duvoux, Christophe; Merle, Jean-Claude; Dannaoui, Eric; Botterel, Françoise

2017-02-01

Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by FKS sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant Candida glabrata, one by resistant Candida dubliniensis, and one by resistant Candida albicans Molecular analysis found three mutations in FKS2 HS1 (F659S, S663A, and D666E) for C. glabrata and one mutation in FKS1 HS1 (S645P) for C. dubliniensis and C. albicans Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in Candida spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment. Copyright © 2017 Prigent et al.

Simultaneous resection for colorectal cancer with synchronous liver metastases is a safe procedure: Outcomes at a single center in Turkey.

PubMed

Dulundu, Ender; Attaallah, Wafi; Tilki, Metin; Yegen, Cumhur; Coskun, Safak; Coskun, Mumin; Erdim, Aylin; Tanrikulu, Eda; Yardimci, Samet; Gunal, Omer

2017-05-23

The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.

The long- and short-term variability of breathing induced tumor motion in lung and liver over the course of a radiotherapy treatment.

PubMed

Dhont, Jennifer; Vandemeulebroucke, Jef; Burghelea, Manuela; Poels, Kenneth; Depuydt, Tom; Van Den Begin, Robbe; Jaudet, Cyril; Collen, Christine; Engels, Benedikt; Reynders, Truus; Boussaer, Marlies; Gevaert, Thierry; De Ridder, Mark; Verellen, Dirk

2018-02-01

To evaluate the short and long-term variability of breathing induced tumor motion. 3D tumor motion of 19 lung and 18 liver lesions captured over the course of an SBRT treatment were evaluated and compared to the motion on 4D-CT. An implanted fiducial could be used for unambiguous motion information. Fast orthogonal fluoroscopy (FF) sequences, included in the treatment workflow, were used to evaluate motion during treatment. Several motion parameters were compared between different FF sequences from the same fraction to evaluate the intrafraction variability. To assess interfraction variability, amplitude and hysteresis were compared between fractions and with the 3D tumor motion registered by 4D-CT. Population based margins, necessary on top of the ITV to capture all motion variability, were calculated based on the motion captured during treatment. Baseline drift in the cranio-caudal (CC) or anterior-poster (AP) direction is significant (ie. >5 mm) for a large group of patients, in contrary to intrafraction amplitude and hysteresis variability. However, a correlation between intrafraction amplitude variability and mean motion amplitude was found (Pearson's correlation coefficient, r = 0.72, p < 10 -4 ). Interfraction variability in amplitude is significant for 46% of all lesions. As such, 4D-CT accurately captures the motion during treatment for some fractions but not for all. Accounting for motion variability during treatment increases the PTV margins in all directions, most significantly in CC from 5 mm to 13.7 mm for lung and 8.0 mm for liver. Both short-term and day-to-day tumor motion variability can be significant, especially for lesions moving with amplitudes above 7 mm. Abandoning passive motion management strategies in favor of more active ones is advised. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative studies on cervical and colonic malignancies using FTIR microspectroscopy

NASA Astrophysics Data System (ADS)

Mordechai, Shaul; Mark, Shlomo; Podshyvalov, A.; Kantarovich, Keren; Bernshtain, Y.; Salman, Ahmad; Erukhimovitch, Vitaly; Guterman, Hugo; Goldstein, Jed; Argov, Shmuel; Jagannathan, R.

2003-07-01

IR spectroscopy provides a new diagnostic tool due to its sensitivity to molecular composition and structure in cells, which accompany transformation from healthy to diseased state. The IR spectrum of a sample is, therefore, a biochemical fingerprint. It has been found that the most significant changes occur in the mid-IR spectral range 3-25 mm. Encouraging results have been reported in the literature on various types of cancers, such as human breast, lung, colon, cervical, and leukemia using FT-IR microspectroscopy. Much progress has also been made by several groups on IR spectral maps and IR imaging with good agreement between the data and the histopathological information. In an attempt to characterize healthy and diseased tissues, infrared microspectroscopy of cervical and colon human tissues was studied using an infrared microscopy. The comparative qualitative and quantitative changes detected using FTIR microspectroscopy are discussed.

Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

PubMed Central

Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin-Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Wei-Zhong; Teng, Xin-Rong; Zhang, Rong-Xuan; Jiang, Dian-hua; Mulet, Xavier; Li, Hui-Ping

2013-01-01

Objective Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice. PMID:23516459

PPARGC1A is upregulated and facilitates lung cancer metastasis.

PubMed

Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

2017-10-15

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty.

PubMed

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2018-05-15

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.

Liver protein synthesis stays elevated after chemotherapy in tumour-bearing mice.

PubMed

Samuels, Sue E; McLaren, Teresa A; Knowles, Andrew L; Stewart, Sarah A; Madelmont, Jean-Claude; Attaix, Didier

2006-07-28

We studied the effect of chemotherapy on liver protein synthesis in mice bearing colon 26 adenocarcinoma (C26). Liver protein mass decreased (-32%; P<0.05) in cachectic mice, but protein synthesis increased (20-35%; P<0.05) in cachectic mice, which is consistent with increased export protein synthesis. Increased protein synthesis in tumour-bearing mice was primarily mediated by increasing ( approximately 15%; P<0.05) the RNA concentration, i.e. the capacity for protein synthesis (Cs; mg RNA/g protein). Cystemustine, a nitrosourea chemotherapy that cures C26 with 100% efficacy, rapidly restored liver protein mass; protein synthesis however stayed higher than in healthy mice ( approximately 15%) throughout the initial and later stages of recovery. Chemotherapy had no significant effect on liver protein mass and synthesis in healthy mice. Reduced food intake was not a factor in this model. These data suggest a high priority for liver protein synthesis during cancer cachexia and recovery.

Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia.

PubMed

Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Davis, J Lucian; Cattamanchi, Adithya; den Boon, Saskia; Yoo, Samuel D; Goodman, Carol D; Huang, Laurence

2012-02-01

Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries. Copyright © 2012 Elsevier Inc. All rights reserved.

Giant colonic volvulus due to colonic pseudo-obstruction

PubMed Central

Karaman, Kerem; Tanoglu, Alpaslan; Beyazit, Yavuz; Han, Ismet

2015-01-01

Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie’s syndrome, is a clinical syndrome characterised by gross dilation of the caecum and right hemicolon, which sometimes extends to the sigmoid colon and rectum in the absence of an anatomic lesion in the intestinal lumen. It is characterised by impaired propulsion of contents of the gastrointestinal tract, which results in a clinical picture of intestinal obstruction. A careful examination of the markedly distended colon can exclude several colonic pathologies, including mechanical obstruction and other causes of toxic megacolon. ACPO can sometimes predispose or mimic colonic volvulus, especially in geriatric patients. PMID:25716038

[Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

PubMed

Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

2015-03-01

Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Modified Liver Hanging Maneuver for En-bloc Right-sided Hepatectomy Combined with Total Caudate Lobectomy for Colon-Cancer Liver Metastasis and Hepatocellular Carcinoma.

PubMed

Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Kikuchi, Yutaro; Endo, Itaru; Koda, Keiji; Togo, Shinji; Hoffman, Robert M; Tanaka, Kuniya

2016-04-01

A right-sided hepatectomy with total caudate lobectomy is indicated for colorectal-cancer liver metastases (CLM) and hepatocellular carcinomas (HCC) located in the caudate lobe with extension to the right lobe of the liver. Caudate-lobe resection (i.e. segmentectomy 1 according to the Brisbane terminology) is one of the most difficult types of hepatectomy to carry out radically and safely. The deep portion of hepatic transection around the caudate lobe, hepatic veins and inferior vena cava is a critical source of massive bleeding. Prolonged transection can increase blood loss. We analyzed the outcome of 10 patients who underwent right-sided hepatectomy with caudate lobectomy using a modified liver hanging maneuver (mLHM) in comparison with 16 patients who underwent the operation without mLHM. Blood loss during liver transection and blood loss per unit area of cut surface were significantly less in the mLHM group (p=0.014 and 0.015, respectively). In patients diagnosed pathologically with liver impairment, transection time was significantly shorter in the mLHM group (p=0.038), as were red blood cell transfusion volume (p=0.042) and blood loss (p=0.049) during transection. Use of mLHM can potentially improve surgical outcomes by reducing blood loss and transection time, which are especially important for patients with liver impairment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis.

PubMed

Venkatachalam, Karthikkumar; Gunasekaran, Sivagami; Jesudoss, Victor Antony Santiago; Namasivayam, Nalini

2013-05-01

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kgb.w.). Groups 3-6 were induced colon cancer by injecting DMH (20 mg/kgb.w.) subcutaneously once a week for the first four weeks (groups 3-6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kgb.w. to groups 4-6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mgkg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kgb.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer. Copyright © 2011 Elsevier GmbH. All rights reserved.

Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy

PubMed Central

Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

2016-01-01

Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy. PMID:27703383

Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy.

PubMed

Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

2016-01-01

Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus -positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy.

TNF-{alpha} similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Lars, E-mail: lars.mueller@uksh-kiel.de; Seggern, Lena von; Schumacher, Jennifer

2010-07-02

Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-{alpha} on the transcript and protein level, whereas PDGF-BB, TGF-{beta}1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparablemore » up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-{alpha}, and of alpha-smooth muscle actin, by TGF-{beta}1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.« less

Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge.

PubMed

Farrell, Helen; Oliveira, Martha; Macdonald, Kate; Yunis, Joseph; Mach, Michael; Bruce, Kimberley; Stevenson, Philip; Cardin, Rhonda; Davis-Poynter, Nicholas

2016-12-01

Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant that human CMV (HCMV) dissemination is not well understood. Murine CMV (MCMV) provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation. Ex vivo luciferase imaging showed greater sensitivity than plaque assay, and revealed both well-known infection sites (the lungs, lymph nodes, salivary glands, liver, spleen and pancreas) and less explored sites (the bone marrow and upper respiratory tract). We applied luciferase imaging to tracking MCMV lacking M33, a chemokine receptor conserved in HCMV and a proposed anti-viral drug target. M33-deficient M78-LUC colonized normally in peripheral sites and local draining lymph nodes but spread poorly to the salivary gland, suggesting a defect in vascular transport consistent with properties of a chemokine receptor.

Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

PubMed

Shankar, J; Nguyen, M H; Crespo, M M; Kwak, E J; Lucas, S K; McHugh, K J; Mounaud, S; Alcorn, J F; Pilewski, J M; Shigemura, N; Kolls, J K; Nierman, W C; Clancy, C J

2016-06-01

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Mutagenicity of 1-nitropyrene metabolites from lung S9.

PubMed

King, L C; Kohan, M J; Ball, L M; Lewtas, J

1984-04-01

The mutagenicity of 1-nitropyrene metabolites from rabbit lung S9 incubates was evaluated using the Salmonella typhimurium plate incorporation assay with strain TA98, with and without Aroclor-induced rat liver S9. The following metabolites were isolated, identified and quantitated by HPLC: 1-nitropyrene -4,5- or -9,10-dihydrodiol (K-DHD), N-acetyl-1-aminopyrene ( NAAP ), 1-aminopyrene (1-AMP), 10-hydroxy-1-nitropyrene, 4-, 5-, 6-, 8- or 9-monohydroxy-1-nitropyrene (phenols) and 3-hydroxy-1-nitropyrene. The predominant metabolites formed by lung S9 incubates were K-DHD, 3-OH-1-nitropyrene and phenols. All of the metabolites were mutagenic in the absence of the exogenous rat liver S9 metabolic activation system, and several, including two unidentified metabolites were more potent than the parent 1-nitropyrene. The mutagenicity of 3 of the metabolites ( NAAP , 10-OH-1-nitropyrene and phenols) were enhanced by S9 while most of the other metabolites were less mutagenic in the presence of S9. These results indicate that lung tissue is capable of both oxidative and reductive metabolism which produced mutagenic metabolites, several of which were more potent than the parent compound, 1-NP.

Recombinant Salmonella expressing SspH2-EscI fusion protein limits its colonization in mice.

PubMed

Hu, Maozhi; Zhao, Weixin; Gao, Wei; Li, Wenhua; Meng, Chuang; Yan, Qiuxiang; Wang, Yuyang; Zhou, Xiaohui; Geng, Shizhong; Pan, Zhiming; Cui, Guiyou; Jiao, Xinan

2017-05-03

Activation of inflammasome contributes to the clearance of intracellular bacteria. C-terminus of E. coli EscI protein can activate NLRC4 (NLR family, CARD domain containing-4) inflammasome in macrophages. The purpose of this study was to determine if activation of NLRC4 inflammasome by EscI can reduce the colonization of Salmonella in mice. A recombinant S. typhimurium strain expressing fusion protein of the N-terminal SspH2 (a Salmonella type III secretion system 2 effector) and C-terminal EscI was constructed and designated as X4550(pYA3334-SspH2-EscI). In vitro assay showed that X4550(pYA3334-SspH2-EscI) significantly enhanced IL-1β and IL-18 secretion (P < 0.05) and pyroptotic cell death of mouse peritoneal macrophages, compared with those infected with control strain, X4550(pYA3334-SspH2). In vivo studies showed that colonization of X4550(pYA3334-SspH2-EscI) in both spleen and liver were significantly lower than that of X4550(pYA3334-SspH2) (P < 0.05). The bacterial counts of X4550(pYA3334-SspH2-EscI) in mice decreased, while those of X4550(pYA3334-SspH2) increased over the time after infection. Additionally, X4550(pYA3334-SspH2-EscI) induced a less pathological alteration in spleen and liver than X4550(pYA3334-SspH2). Fusion protein SspH2-EscI may be translocated into macrophages and activate NLRC4 inflammasome, which limits Salmonella colonization in spleen and liver of mice.

Arsenic Exposure and Cancer Mortality in a US-based Prospective Cohort: the Strong Heart Study

PubMed Central

García-Esquinas, Esther; Pollán, Marina; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Guallar, Eliseo; Howard, Barbara; Farley, John; Yeh, Jeunliang; Best, Lyle G.; Navas-Acien, Ana

2013-01-01

Background Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. Prospective studies on carcinogenic effects at low-moderate arsenic levels are lacking. Methods We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians 45–74 years from Arizona, Oklahoma and North/South Dakota who participated in the Strong Heart Study in 1989–1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, 40 lymphatic/hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate and kidney cancer. Results Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8–15.6) μg/g creatinine. The adjusted hazard ratios (95% CI) comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92–1.41) for overall cancer, 1.56 (1.02–2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28–8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09–5.58) for pancreatic cancer, and 0.46 (0.22–0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. Conclusions Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate and pancreas. Impact These findings support the role of low-moderate arsenic exposure in lung, prostate and pancreas cancer development and can inform arsenic risk assessment. PMID:23800676

Meningitis by Toxocara canis after Ingestion of Raw Ostrich Liver

PubMed Central

Noh, Young; Hong, Sung-Tae; Yun, Ji Young; Park, Hong-Kyun; Oh, Jung-Hwan; Kim, Young Eun

2012-01-01

Recently reports on toxocariasis are increasing by serodiagnosis in Korea. A previously healthy 17-yr-old boy complained of headache, fever, dyspnea, and anorexia. He showed symptoms and signs of eosinophilic meningitis with involvement of the lungs and liver. Specific IgG antibody to Toxocara canis larval antigen was positive in serum and cerebrospinal fluid by ELISA. He took raw ostrich liver with his parents 4 weeks before the symptom onset. His parents were seropositive for T. canis antigen but had no symptoms or signs suggesting toxocariasis. This is the first report of toxocariasis in a family due to ingestion of raw ostrich liver in Korea. PMID:22969260

Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model

PubMed Central

Banks, Leah D.; Amoah, Priscilla; Niaz, Mohammad S.; Washington, Mary K.; Adunyah, Samuel E.; Ramesh, Aramandla

2015-01-01

Colon cancer ranks third in cancer related mortalities in the United States. Many studies have investigated factors that contribute to colon cancer in which dietary and environmental factors have been shown to play an integral role in the etiology of this disease. Specifically, human dietary intake of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) has generated interest in looking at how it exerts its effects in gastrointestinal carcinogenesis. Therefore, the objective of this study was to investigate the preventative effects of olive oil on benzo(a)pyrene [B(a)P]-induced colon carcinogenesis in adult ApcMin mice. Mice were assigned to a control (n =8) or treatment group (n =8) consisting of 25, 50 and 100 μg B(a)P/kg body weight (bw) dissolved in tricaprylin [B(a)P-only group] or olive oil daily via oral gavage for sixty days. Our studies showed that ApcMin mice exposed to B(a)P developed a significantly higher number (p< 0.05) of larger dysplastic adenomas compared to those exposed to B(a)P + olive oil. Treatment of mice with B(a)P and olive oil significantly altered (p< 0.05) the expression of drug metabolizing enzymes in both the colon and liver tissues. However, only GST activity was significantly higher (p< 0.05) in the liver of mice treated with 50 and 100 μg B(a)P/kg bw + olive oil. Lastly, olive oil promoted rapid detoxification of B(a)P by decreasing its organic metabolite concentrations and also decreasing the extent of DNA damage to colon and liver tissues (p< 0.05). These results suggest that olive oil has a protective effect against B(a)P-induced colon tumors. PMID:26878781

[Hepatobronchial Fistula and Lung Abscess after Transarterial Chemoembolization].

PubMed

Lee, Kwanjoo; Song, Jeong Eun; Jeong, Hyang Sook; Kim, Do Young

2017-05-25

Transarterial chemoembolization (TACE) is a common treatment modality to locally manage hepatocellular carcinoma. Liver abscess and bile duct injury are common complications of TACE. However, hepatobronchial fistula is a rare complication. Herein, we report a case of lung abscess due to hepatobronchial fistula after TACE. A 67-year-old man, who had underwent TACE 6 months ago, presented cough and bile-colored sputum. He was diagnosed with lung abscess and hepatobronchial fistula. We performed endoscopic retrograde cholangiopancreatography; however, there was no improvement in his symptoms. Thereafter, partial hepatectomy and repair of fistula were successively conducted.

Decreased expression of peroxisome proliferator activated receptor gamma in cftr-/- mice.

PubMed

Ollero, Mario; Junaidi, Omer; Zaman, Munir M; Tzameli, Iphigenia; Ferrando, Adolfo A; Andersson, Charlotte; Blanco, Paola G; Bialecki, Eldad; Freedman, Steven D

2004-08-01

Some of the pathological manifestations of cystic fibrosis are in accordance with an impaired expression and/or activity of PPARgamma. We hypothesized that PPARgamma expression is altered in tissues lacking the normal cystic fibrosis transmembrane regulator protein (CFTR). PPARgamma mRNA levels were measured in colonic mucosa, ileal mucosa, adipose tissue, lung, and liver from wild-type and cftr-/- mice by quantitative RT-PCR. PPARgamma expression was decreased twofold in CFTR-regulated tissues (colon, ileum, and lung) from cftr-/- mice compared to wild-type littermates. In contrast, no differences were found in fat and liver. Immunohistochemical analysis of PPARgamma in ileum and colon revealed a predominantly nuclear localization in wild-type mucosal epithelial cells while tissues from cftr-/- mice showed a more diffuse, lower intensity labeling. A significant decrease in PPARgamma expression was confirmed in nuclear extracts of colon mucosa by Western blot analysis. In addition, binding of the PPARgamma/RXR heterodimer to an oligonucletotide containing a peroxisome proliferator responsive element (PPRE) was also decreased in colonic mucosa extracts from cftr-/- mice. Treatment of cftr-/- mice with the PPARgamma ligand rosiglitazone restored both the nuclear localization and binding to DNA, but did not increase RNA levels. We conclude that PPARgamma expression in cftr-/- mice is downregulated at the RNA and protein levels and its function diminished. These changes may be related to the loss of function of CFTR and may be relevant to the pathogenesis of metabolic abnormalities associated with cystic fibrosis in humans. Copyright 2004 Wiley-Liss, Inc.

Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary morbidity in congenital diaphragmatic hernia (CDH).

PubMed

Zamora, Irving J; Olutoye, Oluyinka O; Cass, Darrell L; Fallon, Sara C; Lazar, David A; Cassady, Christopher I; Mehollin-Ray, Amy R; Welty, Stephen E; Ruano, Rodrigo; Belfort, Michael A; Lee, Timothy C

2014-05-01

The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity. The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD. Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30 vs.42%; p=0.001) and higher %LH (21.3±2.8 vs.7.1±1.8%; p<0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV<35% (AUC=0.74; p<0.001) and %LH>20% (AUC=0.78; p<0.001). On logistic regression, O/E-TFLV<35% and a %LH>20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5-48.9, p=0.002). Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Liver resection for colorectal cancer metastases

PubMed Central

Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

2013-01-01

Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

PubMed

Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

2016-10-01

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty

PubMed Central

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2017-01-01

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma. PMID:29279503

Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

PubMed

Aizawa, Koichi; Liu, Chun; Tang, Sanyuan; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

2016-09-01

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury. © 2016 UICC.

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study.

PubMed

Lee, Karla C L; Baker, Luisa A; Stanzani, Giacomo; Alibhai, Hatim; Chang, Yu Mei; Jimenez Palacios, Carolina; Leckie, Pamela J; Giordano, Paola; Priestnall, Simon L; Antoine, Daniel J; Jenkins, Rosalind E; Goldring, Christopher E; Park, B Kevin; Andreola, Fausto; Agarwal, Banwari; Mookerjee, Rajeshwar P; Davies, Nathan A; Jalan, Rajiv

2015-09-01

In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure. Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure. The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen. The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AMPK/p53 Axis Is Essential for α-Lipoic Acid-Regulated Metastasis in Human and Mouse Colon Cancer Cells.

PubMed

Park, Sunmi; Choi, Seung Kug; Choi, Yura; Moon, Hyun-Seuk

2015-10-01

α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.

Colon cancer - resources

MedlinePlus

Resources - colon cancer ... The following organizations are good resources for information on colon cancer : American Cancer Society -- www.cancer.org/cancer/colon-rectal-cancer.html Colon Cancer Alliance -- www.ccalliance. ...

SU-F-T-687: Comparison of SPECT/CT-Based Methodologies for Estimating Lung Dose from Y-90 Radioembolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kost, S; Yu, N; Lin, S

2016-06-15

Purpose: To compare mean lung dose (MLD) estimates from 99mTc macroaggregated albumin (MAA) SPECT/CT using two published methodologies for patients treated with {sup 90}Y radioembolization for liver cancer. Methods: MLD was estimated retrospectively using two methodologies for 40 patients from SPECT/CT images of 99mTc-MAA administered prior to radioembolization. In these two methods, lung shunt fractions (LSFs) were calculated as the ratio of scanned lung activity to the activity in the entire scan volume or to the sum of activity in the lung and liver respectively. Misregistration of liver activity into the lungs during SPECT acquisition was overcome by excluding lungmore » counts within either 2 or 1.5 cm of the diaphragm apex respectively. Patient lung density was assumed to be 0.3 g/cm{sup 3} or derived from CT densitovolumetry respectively. Results from both approaches were compared to MLD determined by planar scintigraphy (PS). The effect of patient size on the difference between MLD from PS and SPECT/CT was also investigated. Results: Lung density from CT densitovolumetry is not different from the reference density (p = 0.68). The second method resulted in lung dose of an average 1.5 times larger lung dose compared to the first method; however the difference between the means of the two estimates was not significant (p = 0.07). Lung dose from both methods were statistically different from those estimated from 2D PS (p < 0.001). There was no correlation between patient size and the difference between MLD from PS and both SPECT/CT methods (r < 0.22, p > 0.17). Conclusion: There is no statistically significant difference between MLD estimated from the two techniques. Both methods are statistically different from conventional PS, with PS overestimating dose by a factor of three or larger. The difference between lung doses estimated from 2D planar or 3D SPECT/CT is not dependent on patient size.« less

Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells.

PubMed

Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M; Ezekiel, Uthayashanker R

2016-01-01

We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer.

Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery

NASA Astrophysics Data System (ADS)

Zhou, Jihan; Li, Dong; Wen, Hao; Zheng, Shuquan; Su, Cuicui; Yi, Fan; Wang, Jue; Liang, Zicai; Tang, Tao; Zhou, Demin; Zhang, Li-He; Liang, Dehai; Du, Quan

2016-03-01

Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.

Successful Osimertinib Rechallenge with Steroid Therapy after Osimertinib-induced Interstitial Lung Disease.

PubMed

Kiriu, Tatsunori; Tamura, Daisuke; Tachihara, Motoko; Sekiya, Reina; Hazama, Daisuke; Katsurada, Masahiro; Nakata, Kyosuke; Nagano, Tatsuya; Yamamoto, Masatsugu; Kamiryo, Hiroshi; Kobayashi, Kazuyuki; Nishimura, Yoshihiro

2018-01-01

A 62-year-old male with lung adenocarcinoma harboring an exon 19 deletion in the Epidermal growth factor receptor (EGFR) was treated with EGFR-tyrosine kinase inhibitors (TKIs) and several cytotoxic agents. After administering a fifth-line chemotherapy regimen, a liver biopsy revealed a diagnosis of recurrence with a T790M mutation. After an 82-day course of osimertinib therapy, the patient developed osimertinib-induced interstitial lung disease (ILD). Osimertinib was discontinued, and oral prednisolone was started. The ILD quickly improved, but liver metastases progressed and osimertinib was restarted concurrently with prednisolone. The patient showed neither disease progression nor a recurrence of ILD at 5 months. In situations in which no alternative treatment is available, osimertinib rechallenge should thus be considered as an alternative treatment.

Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

PubMed Central

Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

2014-01-01

Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

PubMed

Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling.

PubMed

Sonoshita, Masahiro; Aoki, Masahiro; Fuwa, Haruhiko; Aoki, Koji; Hosogi, Hisahiro; Sakai, Yoshiharu; Hashida, Hiroki; Takabayashi, Arimichi; Sasaki, Makoto; Robine, Sylvie; Itoh, Kazuyuki; Yoshioka, Kiyoko; Kakizaki, Fumihiko; Kitamura, Takanori; Oshima, Masanobu; Taketo, Makoto Mark