Apoptosis by death factor.

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.

https://science.sciencemag.org/content/sci/267/5203/1449.full.pdf

The Fas Death Factor

https://www.hal.inserm.fr/inserm-00561753/document

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DNA and its DNase activity. When CAD is expressed with ICAD in COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.

A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD

A critical event during programmed cell death (PCD) appears to be the acquisition of plasma membrane (PM) changes that allows phagocytes to recognize and engulf these cells before they rupture. The majority of PCD seen in higher organisms exhibits strikingly similar morphological features, and this form of PCD has been termed apoptosis. The nature of the PM changes that occur on apoptotic cells remains poorly defined. In this study, we have used a phosphatidylserine (PS)-binding protein (annexin V) as a specific probe to detect redistribution of this phospholipid, which is normally confined to the inner PM leaflet, during apoptosis. Here we show that PS externalization is an early and widespread event during apoptosis of a variety of murine and human cell types, regardless of the initiating stimulus, and precedes several other events normally associated with this mode of cell death. We also report that, under conditions in which the morphological features of apoptosis were prevented (macromolecular synthesis inhibition, overexpression of Bcl-2 or Abl), the appearance of PS on the external leaflet of the PM was similarly prevented. These data are compatible with the notion that activation of an inside-outside PS translocase is an early and widespread event during apoptosis.

https://rupress.org/jem/article-pdf/182/5/1545/1107564/1545.pdf

Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.

DURING mammalian development, many cells are programmed to die1,2 most mediated by apoptosis3. The Fas antigen4 coded by the structural gene for mouse lymphoproliferation mutation (lpr)5,6, is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family7,8, and mediates apoptosis7. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary8. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (Mr 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lprcg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lprcg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.

Lethal effect of the anti-Fas antibody in mice

Background:

The purpose of the present study was to evaluate the usefulness of intraoperative imprint cytology and frozen sectioning of sentinel lymph nodes in patients with clinically node-negative breast cancer.



Methods:

Sentinel node biopsy was performed in 101 patients with stage I or II breast cancer with clinically negative nodes using a dye-guided method. Intraoperative evaluation of sentinel node involvement by imprint cytology and frozen sectioning was compared with the final histopathological results of permanent sections. Tumour-negative nodes in paraffin sections stained by haematoxylin and eosin were further studied using an anticytokeratin antibody.



Results:

The results of imprint cytology and frozen-section analysis were compared with those of haematoxylin and eosin-stained sections. The sensitivity, specificity and overall accuracy of imprint cytology were 96·0, 90·8 and 92·1 per cent respectively, and those of frozen-section examination were 52·0, 100 and 88·1 per cent. Ten sentinel nodes were tumour positive on imprint cytology and tumour negative on stained paraffin sections. Micrometastasis was found in eight of these nodes on immunohistochemistry. Taking these immunohistological results into consideration, the final sensitivity, specificity and overall accuracy of imprint cytology were 90·9, 98·5 and 96·0 per cent respectively.



Conclusion:

Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning. © 2000 British Journal of Surgery Society Ltd

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery.

The purpose of this study was to determine whether thin-section CT could be used to differentiate small localized bronchioloalveolar carcinoma from peripheral adenocarcinoma having a bronchioloalveolar (replacement) growth pattern of alveolar lining cells and from adenocarcinoma not having a replacement growth pattern on the basis of the extent of ground-glass opacity revealed by thin-section CT.One hundred twenty-four small, surgically resected, peripheral adenocarcinomas from 119 patients (67 men and 52 women; mean age, 60 years) were studied. Lesion diameters were 0.4-2.0 cm (median, 1.5 cm). The extent of ground-glass opacity within lesions on preoperative thin-section CT was reviewed retrospectively by three thoracic radiologists. On the basis of replacement growth of alveolar lining cells, small adenocarcinomas were classified histologically as localized bronchioloalveolar carcinomas (n = 42) or as adenocarcinomas with (n = 53) or without (n = 29) a replacement growth pattern of alveolar lining cell...

https://www.ajronline.org/doi/pdfplus/10.2214/ajr.173.2.10430155

Ground-glass opacity on thin-section CT: value in differentiating subtypes of adenocarcinoma of the lung.

Background: We aimed to evaluate whether dye-guided sentinel node biopsy is a useful indi­ cator of axillary node involvement in breast cancer patients and whether clinicopathological features affect its success in identifying sentinel nodes. Methods: Sentinel node biopsy was performed in patients with stage I or II breast cancer using an indocyanin green dye-guided method. Results: We could identify sentinel nodes in 127 (73.8%) of 172 patients. The mean number of sentinel nodes per patient was 1.7 (range, 1-8) and the mean node size was 9.3 mm (range, 3.0-28.0 mm). Of the 127 patients, 40 (31.5%) also had axillary node involvement. In 16 (40.00/0) of these, the sentinel node was the only node involved. There was concordance between sentinel node and axillary node status in 122 (96.1%) of the 127 patients. Success in identifying sentinel nodes was not affected by tumor size, operative procedure, histological type of tumor or tumor location; however, the success rate was significantly lower in patients with axillary node involvement (65.7 vs 79.0% in axillary node-negative patients, p= 0.039) and the presence or absence of lymphatic or vascular invasion in the tumor (63.8 vs 78.9% in patients without lymphatic or vascular invasion, p = 0.043). Sentinel nodes could also be iden­ tified significantly more frequently in patients under 50 years old (83.3%) than in those over 50 years old (64.8%, p = 0.009). Conclusions: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable success rate in detecting sentinel nodes and predicting axillary nodal status. Axillary node status, the presence or absence of lymphatic or vascular invasion in the tumor and patient age affect its success in identifying sentinel nodes.

Tsutomu Kasugai

Papers

Lethal effect of the anti-Fas antibody in mice

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery.

Ground-glass opacity on thin-section CT: value in differentiating subtypes of adenocarcinoma of the lung.

Sentinel Node Biopsy Guided by Indocyanin Green Dye in Breast Cancer Patients

Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus.