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.

Intraoperative imprint cytology for the detection of sentinel lymph node metastases in breast cancer

A 76-year-old Japanese man was admitted to Kosei-Nenkin Hospital (Osaka, Japan) in November 2006; his chief complaint was a 10-kg loss in body weight over 3 months prior to admission. Abdominal computed tomography (CT) and dynamic magnetic resonance imaging (MRI) showed three masses in the retroperitoneum. The patient subsequently underwent surgery. The final histopathological diagnosis of tumors 1 and 2 was malignant fibrous histiocytoma of the retroperitoneum, and tumor 3 was a well-differentiated liposarcoma. By the presence of the liposarcoma, tumor 1 and 2 were thought to be the dedifferentiated areas of liposarcomas. At the age of 16, the patient had been exposed to radiation from the atomic bomb at Hiroshima towards the end of the Second World War. We postulate that in this case, radiation from the atomic bomb may have played an important role in the development of the sarcomas.

/pdf/dedifferentiated-liposarcoma-in-the-retroperitoneum-in-an-201q4i1yk3.pdf

Dedifferentiated liposarcoma in the retroperitoneum in an atomic bomb survivor: report of a case.

Methylcobalamin (MeCbl) is an important enzyme cofactor required for methionine synthase activity. It also inhibits, in a dose-dependent manner, the proliferation of an androgen-dependent cell line, SC-3, derived from an androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). In SC-3 cells, androgen induces the production of androgen-induced growth factor (AIGF), an autocrine growth factor increasing the proliferation of SC-3 cells. MeCbl treatment suppressed the androgen-induced, AIGF-mediated growth of SC-3 cells, as well as the androgen-induced increase of AIGF mRNA. In SC-3 cells, androgen receptors linked with androgen form complexes that tightly bind DNA and act as transcription factors in the nucleus to regulate the expression of specific genes such as AIGF. The number and dissociation constants of androgen receptors in control and MeCbl-treated SC-3 cells were the same. Similarly, the extent of binding of normal androgen receptors in nuclei from control and MeCbl-treated cells was virtually identical. The androgen receptors from control and MeCbl-treated cells showed similar capacities for conversion to a form that tightly binds to DNA on heat activation. These results suggest that the reduction of AIGF mRNA, subsequent to the nuclear binding of androgen receptors, may be a partial cause of the growth-inhibitory activity of MeCbl in SC-3 cells.

Methylcobalamin decreases mRNA levels of androgen-induced growth factor in androgen-dependent Shionogi carcinoma 115 cells.

http://rd.springer.com/content/pdf/10.1007%2FBF02967996.pdf

Symposium I Controversies in Sentinel Node Biopsy for Breast Cancer

Mast cells are a progeny of multipotential hematopoietic stem cells. However, the differentiation processes of mast cells are unique and different from those of other progenies of stem cells. First, we will describe the unique differentiation processes of mast cells. In contrast with the unique differentiation processes, regulation mechanisms of mast-cell differentiation appear to be comparable to those of other progenies of hematopoietic stem cells. Second, we will describe regulation mechanisms of mast-cell differentiation. Mast cells are observed in various tissues of the body, and phenotypes of mast cells are different from tissue to tissue. However, the phenotypes of mast cells are not rigidly determined, and can be changed with experimental manipulations. Third, we will describe the phenotypic change between mast-cell subpopulations.

Tsutomu Kasugai

Papers

Intraoperative imprint cytology for the detection of sentinel lymph node metastases in breast cancer

Dedifferentiated liposarcoma in the retroperitoneum in an atomic bomb survivor: report of a case.

Methylcobalamin decreases mRNA levels of androgen-induced growth factor in androgen-dependent Shionogi carcinoma 115 cells.

Symposium I Controversies in Sentinel Node Biopsy for Breast Cancer

Differentiation of Mast Cells and Phenotypic Change Between Subpopulations