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Pathology and genetics of tumours of the lung , pleura, thymus and heart

A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis and angiogenesis, and increased understanding of these roles sets the stage for developing pharmaceutical agents that target these molecules. Such novel agents might be used alone or in combination with operative and/or chemoradiation strategies for treating cancer.

The sweet and sour of cancer: glycans as novel therapeutic targets.

Fibroblast growth factors (FGFs) are thought to influence many processes in vertebrate development because of their diverse sites of expression and wide range of biological activities in in vitro culture systems. As a means of elucidating embryonic functions of FGF-4, gene targeting was used to generate mice harboring a disrupted Fgf4 gene. Embryos homozygous for the null allele underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. As was consistent with their behavior in vivo, Fgf4 null embryos cultured in vitro displayed severely impaired proliferation of the inner cell mass, whereas growth and differentiation of the inner cell mass were rescued when null embryos were cultured in the presence of FGF-4 protein.

https://science.sciencemag.org/content/sci/267/5195/246.full.pdf

Requirement of FGF-4 for postimplantation mouse development

The blood-brain barrier (BBB), a unique selective barrier for the central nervous system (CNS), hinders the passage of most compounds to the CNS, complicating drug development. Innovative in vitro models of the BBB can provide useful insights into its role in CNS disease progression and drug delivery. Static transwell models lack fluidic shear stress, while the conventional dynamic in vitro BBB lacks a thin dual cell layer interface. To address both limitations, we developed a microfluidic blood-brain barrier (μBBB) which closely mimics the in vivo BBB with a dynamic environment and a comparatively thin culture membrane (10 μm). To test validity of the fabricated BBB model, μBBBs were cultured with b.End3 endothelial cells, both with and without co-cultured C8-D1A astrocytes, and their key properties were tested with optical imaging, trans-endothelial electrical resistance (TEER), and permeability assays. The resultant imaging of ZO-1 revealed clearly expressed tight junctions in b.End3 cells, Live/Dead assays indicated high cell viability, and astrocytic morphology of C8-D1A cells were confirmed by ESEM and GFAP immunostains. By day 3 of endothelial culture, TEER levels typically exceeded 250 Ω cm2 in μBBB co-cultures, and 25 Ω cm2 for transwell co-cultures. Instantaneous transient drop in TEER in response to histamine exposure was observed in real-time, followed by recovery, implying stability of the fabricated μBBB model. Resultant permeability coefficients were comparable to previous BBB models, and were significantly increased at higher pH (>10). These results demonstrate that the developed μBBB system is a valid model for some studies of BBB function and drug delivery.

Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB)

Prognostic Factors in Non-small Cell Lung Cancer: A Decade of Progress

UNLABELLED In non-small cell lung cancer (NSCLC), pleural effusion is a frequently observed complication, and often provides a treatment difficulties. The aim of this study is to evaluate prognostic significance of pleural effusion in patients with NSCLC. MATERIALS AND METHODS Seven hundred and eight untreated patients with NSCLC who were consecutively admitted to our department over a 20 year period up to December 1996, were analyzed using uni- and multivariate analyses. RESULTS Univariate analysis showed pleural effusion to be a significant prognostic factor for NSCLC, in addition to gender, stage, performance status(PS). Multivariate analysis proved pleural effusion to be one of the significant prognostic factors, especially in patients with poor PS. CONCLUSION Adequate palliative care to provide prolonged quality survival remains the primary goal of therapy for patients with poor performance status and pleural effusion until better treatments are developed.

Pleural effusion as a significant prognostic factor in non-small cell lung cancer.

Background Metastatic involvement of the pancrease is not an uncommon autopsy finding, however, pancreatic metastasis is an infrequent clinical condition and the pattern of the metastases have not been studied. We conducted a retrospective study in order to evaluate the pattern of the metastasis from lung cancer. Patients From 1976 to 1997, 26 patients with pancreatic metastasis were identified by searching the medical records of 850 patients with lung cancer. Results The usual pattern of pancreatic metastasis involved a solitary nodule in 19 patients (73.1%); multiple nodules in 3(11.5%), and diffuse swelling in 4(15.4%). Nineteen(73.1%) and 18(69.2%) of 26 patients had liver and adrenal gland metastases, respectively. Conclusions Pancreatic metastasis represents a common site of extrathoracic spread of disease for the small number of patients with advanced lung cancer, especially in small cell lung cancer. The usual pattern of the metastasis is a solitary nodule. In order to diagnose exactly, abdominal CT scan would be helpful in such metastasis.

Patterns of pancreatic metastasis from lung cancer.

Propylthiouracil (PTU) is known to cause vasculitis as a rare complication. We report the case of a patient who developed alveolar haemorrhage and haematuria whilst treated with PTU. The serum was positive for antineutrophil cytoplasmic antibody (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). All symptoms resolved completely after discontinuation of PTU. Alveolar haemorrhage or pulmonary-renal syndrome associated with antineutrophil cytoplasmic antibody with myeloperoxidase specificity may be a new complication of propylthiouracil therapy.

https://erj.ersjournals.com/content/erj/10/6/1405.full.pdf

Propylthiouracil-induced alveolar haemorrhage associated with antineutrophil cytoplasmic antibody

A protein encoded by an hst-1 transforming gene was expressed in silkworm-derived BmN cells and secreted into the culture medium using a recombinant baculovirus vector. The strong affinity for heparin of the secreted protein made it possible to purify the hst-1 protein to homogeneity in a two-step procedure. The purified hst-1 protein has a molecular weight of 18,000 and stimulates both DNA synthesis in NIH3T3 cells and human umbilical vein endothelial cell proliferation. In addition, morphological changes and anchorage-independent growth of NIH3T3 cells are induced by this product. These results show that the hst-1 transforming protein is a novel heparin-binding growth factor as predicted by nucleotide sequence analysis.

hst-1 transforming protein: expression in silkworm cells and characterization as a novel heparin-binding growth factor.

To evaluate the correlation between serum levels of sialyl Lewis X-i antigen and distant metastasis and survival in patients with non-small cell lung cancer (NSCLC), we measured the serum levels of the tumor marker in 371 patients with untreated NSCLC. The sialyl Lewis X-i antigen level was measured using a RIA kit. In patients with adenocarcinoma or other NSCLC subtypes, there was a correlation between serum sialyl Lewis X-i antigen and stage of the disease (P = 0.0001 and P = 0.0015, respectively). Levels of the marker varied significantly depending on the number of metastatic organs in adenocarcinoma (P = 0.0089) and in other NSCLC subtypes (P = 0.002). Univariate analysis showed that survival of NSCLC patients with high (more than 100 units/ml) sialyl Lewis X-i antigen levels was significantly poorer than that of patients with low antigen levels (P = 0.0001). Multivariate analysis using Cox's proportional hazard model showed that high sialyl Lewis X-i antigen levels correlated significantly with poor survival (P = 0.004). Our data suggest that a high serum level of sialyl Lewis X-i antigen seems to be an indicator of the presence of metastasis and might indicate the need for a careful investigation of all putative metastatic sites. The serum levels of sialyl Lewis X-i antigen may reflect the extension of metastasis and would be helpful in considering treatment options.

https://clincancerres.aacrjournals.org/content/clincanres/3/4/495.full.pdf

Yuko T. Yamashita

Papers

Pleural effusion as a significant prognostic factor in non-small cell lung cancer.

Patterns of pancreatic metastasis from lung cancer.

Propylthiouracil-induced alveolar haemorrhage associated with antineutrophil cytoplasmic antibody

hst-1 transforming protein: expression in silkworm cells and characterization as a novel heparin-binding growth factor.

Serum sialyl lewis X-i antigen levels in non-small cell lung cancer: correlation with distant metastasis and survival.