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ADP-ribosylation, DNA repair, cell differentiation and cancer.
This review discusses the potential relationships between ADP-ribosylation reactions, DNA repair, cell differentiation, and cancer. ADP-ribosylation of chromatin proteins has been shown to participate in DNA excision repair in all nucleated cells. ADP-ribosylation of chromatin proteins is catalysed by nuclear ADP-ribosyl transferase (ADPRT). This enzyme is entirely dependent on DNA for its activity because it has an absolute requirement for ends or nicks in double-stranded DNA. Exposure of cells to small alkylating agents or to radiation causes a fall in cellular NAD+ levels due to a transient activation of ADPRT and a consequent ADP-ribosylation of chromatin proteins. Inhibitors of ADPRT retard DNA strand-rejoining induced by radiation or by small alkylating agents; such inhibition has at least two biological consequences; a synergistic potentiation of cytotoxicity and an enhancement of sister chromatid exchanges and chromosomal aberrations. No species differences have yet been reported; there are variations between cell types and between different damaging agents. The enzyme inhibitors do not block early steps in DNA repair, and repair synthesis does not require ADPRT activity. DNA damage increases the activity of both DNA polymerase beta and DNA ligase II. The activation of DNA ligase II can be blocked by ADPRT inhibitors; presumably ADPRT activity is required for the activation of DNA ligase II. A plausible molecular explanation for the function of ADPRT in DNA repair is that ADPRT regulates the activity of DNA ligase II, the "non-replicative" ligase. In addition to its function in DNA repair, ADPRT is an obligatory requirement in certain categories of cell differentiation. Inhibitors of ADPRT and nicotinamide starvation both reversibly block cell differentiation. We suggest that a similar mechanism to that of DNA repair may be involved because we observe 100 to 300 single-strand DNA breaks during the cytodifferentiation of primary chick myoblasts. These breaks are not due to a general deficiency in DNA repair. I suggest that in certain categories of cell differentiation there are rearrangements or transpositions within the mammalian genome, and that ADP-ribosylation reactions have a general function to be sensitive to DNA breaks and to regulate subsequent DNA ligation in DNA repair, in DNA recombination, in sister chromatid exchanges, in chromosome aberrations, in gene rearrangements, in transpositions and in certain categories of cell differentiation. The relevance of these observations and ideas to cancer is discussed.
[Abrikosov's myoblastoma granular].
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[A resected case of granular cell tumor occurring in the right main bronchus and on the tongue].
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[Measurement of bioimpedance in cryosurgery. Experimental and clinical study].
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[Unusual tremor in a patient with a local lesion of the brain].
The authors describe tremor of the left limbs, that differs from the known types of tremor. The patient developed it concurrently with the symptoms of meningioma of the anterior part of the falciform process in the presence of residual phenomena after removal of the lateral ventricle tumor. The pathophysiological mechanisms of this unusual tremor generation are discussed.
Symmetrical muscle contractures in tumorous sarcoidosis: report of a case.
A 25-year-old woman had symmetrical contractures of the gastrocnemii with a large firm swelling in both medial heads. The contractures insidiously increased over the previous six months. Roentgenograms of the chest showed hilar lymphadenopathy but investigations were otherwise negative. Biopsy showed this to be tumorous sarcoidosis. Both tendoachilles were lengthened. Spontaneous regression of the abnormal muscle masses subsequently occurred without further treatment. Tumorous sarcoidosis is a rare entity, and there have been very few previous reports of muscle contractures having occurred associated with sarcoidosis.
[Computerized tomography of mediastino-retroperitoneal angiomatosis].
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[Proceedings of the 28th annual musculoskeletal tumor meeting of the Japanese Orthopaedic Association. Abstracts].
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[Unusual benign lesion of the thoracic wall. Abrikossoff's myoblastoma. Diagnostic imaging contribution].
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[Magnetic resonance tomography and computerized tomography in tumor staging of mouth and oropharyngeal cancer].
30 patients with malignant tumours of the cavum oris and oropharynx were examined by MRI and CT to compare their accuracy for T-staging. There was histological information in all cases. Histological studies showed an accuracy in T-staging of 81% for MRI and 77% for CT. Differentiation between stages T2/T3 and T3/T4 is possible in 80% by CT and 84% by MRI. Tumours of the cavum oris and oropharynx of T1-stage are possible only in 1 of 3 cases. The use of T2-weighted sequences allows the best frequence of tumour representation in 89%. CT shows an earlier bone involvement than MRI. In addition, the ability to produce coronal and sagittal images by MRI makes it superior to CT in judging tumour extension.
Platysma myocutaneous flap for intraoral and surface reconstruction.
Different procedures have been described for facial and oral reconstruction after malignant tumor removal, such as skin grafts and local and distal staged flaps. Myocutaneous island or free flaps are the method of choice for these reconstructions. Our experience concerns the use of the platysma myocutaneous flap in 12 patients after intraoral and extraoral malignant tumor resection. Six patients had squamous cell carcinomas, i.e., 2 malignant melanomas of the skin and 4 squamous cell carcinomas of the oral mucosa. The complete tumor resection was controlled by frozen-section biopsy in all patients, but for 7 of them a functional or radical neck dissection was performed. We suggest including in the flap the external jugular vein. The results were evaluated from an oncological, functional, and aesthetic point of view. We noticed 2 recurrences in a minimum follow-up of 4 years. The functional and aesthetic results were quite satisfactory and no serious complications were noticed in our series. However, the primary disadvantage of this interesting flap is that the dominant vasculature derived from the submental branch of the facial artery is seldom visualized. In spite of this, it should be regarded as very useful for limited intraoral or surface coverage problems in an arc extending 10 cm from the level of the facial artery at the mandible. This arc includes the cheek, the lower lip, the chin, the floor of the mouth, and the mastoid area.
Ethmoidal myofibroblastoma.
Myofibroblastoma is an uncommon mesenchymal tumour characterized by spindle cells exhibiting the ultrastructural and immunohistochemical features of myofibroblasts. We report a case of a myofibroblastoma occurring in the ethmoid sinus, which to our knowledge is the first case reported in the literature. The clinical presentation, diagnosis, histology, and management of this lesion is discussed with a review of the relevant literature.
The staging and surgery of musculoskeletal neoplasms.
This review has outlined the surgical staging of benign and malignant musculoskeletal neoplasms. Based on their unique natural history, these neoplasms behave in a predictable fashion. The surgical staging system assigns progressively higher degrees of risks to the neoplasms based on their surgical grade, their anatomic location, and the presence or absence of metastases. The staging system articulates well with preoperative planning, defining the margins needed for local tumor control. Because surgery distorts most of the imaging modalities available, all clinical staging studies must be completed before surgical intervention. As more data accrue as to the importance of DNA ploidy, genetic markers, and other characteristics, it is likely they will play an important role in the diagnosis and treatment of musculoskeletal neoplasms in the future.
Expression of transduced carcinoembryonic antigen gene in human rhabdomyosarcoma inhibits metastasis.
Carcinoembryonic antigen (CEA) is a highly glycosylated cell surface glycoprotein belonging to the immunoglobulin superfamily. CEA has been involved in vitro in adhesion mechanisms, but little is known about the function of this glycoprotein in vivo in normal tissue differentiation and malignancy. With regard to the relationship between CEA expression and tissue differentiation, it has been reported that transfection of the CEA gene in rat L6 myoblasts results in a complete block of myogenic differentiation. To extend investigations to the transformed myogenic counterpart and examine CEA effects on differentiation and malignancy outside the colon system, we have transfected the human CEA gene in human rhabdomyosarcoma cells. Human rhabdomyosarcoma cells transfected with the CEA gene correctly expressed membrane CEA anchored via glycosylphosphatidylinositol and secreted CEA in the medium. CEA gene transfer in human rhabdomyosarcoma cells, which display a limited differentiation ability, does not further inhibit myogenic differentiation or alter in vitro proliferation or natural killer sensitivity. CEA transfection does not affect s.c. growth in nude mice, but the ectopic expression of CEA in human rhabdomyosarcoma cells can strongly inhibit their metastatic ability to lungs and adrenals after i.v. injection. The impairment of metastatic potential correlates with a reduction in the homotypic adhesion properties of the cells. These data suggest that CEA, in some systems, can interfere with intercellular adhesion and, at least for cells not metastatic to the liver, can act as an anti-metastatic molecule.
Re: Samuel D, Thomas DM, Tiernay PA, et al. Ethmoidal myofibroblastoma. J Otolaryngol 1995; 24:313-316.
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Case report of intramuscular myxoma with review of literature.
This is a case report of a lady who presented with mass in the abdominal wall, clinically diagnosed as neurofibroma. On histological examination it was proven to be an intramuscular myxoma. Since it is rare it was thought relevant to report this case.
Staging systems for musculoskeletal neoplasia.
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