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[en] Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management
[en] Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients
[en] TO THE EDITOR: The recent article by Demir et al. in your esteemed journal provided for highly stimulating and interesting reading. Interestingly, over the past few years artemin has been identified as a significant player in the enhancement of oncogenicity of various other tumors besides pancreatic cancers.
[en] The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (r_s=0.283, P=0.049) and serum albumin (r_s=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; r_s=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE
[en] Duplication of vertebral arteries is a very rare but clinically important condition. A duplicated vertebral artery origin can influence hemodynamics, pathogenesis of vascular lesions and treatment options. In cases of vertebral artery duplication, the vertebral arteries generally enter the transverse foramen higher up than normal. Awareness of these vertebral artery variants before procedures, such as neurointervention or surgery, may be beneficial. Here, we describe a case of a 51-year-old female patient with left vertebral artery duplication which was detected incidentally.
[en] Objective. To review our experience of chronic recurrent multifocal osteomyelitis (CRMO) and to assess the value of MRI in this rare disease, which mainly affects children and adolescents. Design and patients. Seventeen patients from our departments were reviewed. All underwent conventional radiography and MRI, and most had bone scintigraphy. All had undergone bone biopsy, with microbiological and histopathological examinations, to exclude infectious disease, tumours and tumour-like lesions. Results and conclusion. CRMO affects predominantly the tubular bones of the limbs, followed by the clavicle and the spine. Other locations are rare. Diagnosis is important in avoiding unnecessary diagnostic procedures and to initiate appropriate therapy, and is usually based on a characteristic course and the appearances on radiography. However, CRMO lesions of tubular bones and the spine exhibit quite characteristic MRI features which support the diagnosis, while the appearance of the early clavicular lesion is non-specific. At all sites of CRMO in the skeleton, MRI is valuable in assessing the extent and activity of the lesion. It may exclude pyogenic involvement of the bone and soft tissues and guide effective biopsy. (orig.). With 10 figs., 1 tab
[en] The recent article by Wang et al. () was highly interesting. Interestingly, recent data suggests that Skp2 expression may play a significant role in the etio-pathogenesis of a number of systemic malignancies besides breast carcinomas.
[en] Shoulder joints of 149 Beagles over 8 years old at the time of death (mean age, 13.8 years +/- 3.21), were examined radiographically throughout their life-times for the frequency of degenerative joint disease (DJD). Clinical histories revealed no underlying cause for DJD. The shoulder joints of a subgroup of 18 dogs were examined at necropsy, and thin sections of the joints were evaluated radiographically and histologically. Serial clinical radiographic studies indicated that normal shoulder joint development during the first year of life was followed by the appearance of subchondral bone sclerosis and bony remodeling of normal joint contour, and by the formation of periarticular osteophytes and enthesiophytes. All changes were progressive with age and typical for DJD in dogs. Bilateral involvement was common. Evaluation of specimens obtained at necropsy revealed: articular cartilage change with roughening of the surface layer, degeneration and death of superficial chondrocytes, exposure of deeper layers of chondrocytes that had proliferated with fissuring of the damaged cartilage, total cartilage loss with polishing of the exposed subchondral bone, mixed patterns of subchondral bone sclerosis and osteoporosis, change in contour of the articular surfaces, and formation of periarticular osteophytes and enthesiophytes. Joint capsule thickening, synovitis, pannus formation, and synovial chondroma formation were observed. Because of the available clinical information, in addition to the typical changes of DJD, it was thought that the changes were primary. Instability appeared to play a role in the pathogenesis of the joint disease described; however, it was not clear whether the instability caused abnormal forces on healthy cartilage or whether the primary cartilage wear caused the instability
[en] There will be over 160,000 cases of lung cancer diagnosed in the US in 1991, and deaths from this disease account for a quarter of all cancer deaths in this country. The incidence of lung cancer has continued to increase, especially among women. With 31% of American men and 25% of American women identified in the 1985 census as cigarette smokers, it is likely that this trend will continue well into the next century. Unfortunately, the majority of patients present with locally advanced tumors or distant metastatic disease. Presently, most patients with lung cancer will receive radiation therapy either in an attempt to control inoperable or locally advanced disease, or for palliation of symptomatic intrathoracic or metastatic disease. Because of the poor prognosis of all patients excepting those with early stage resectable lesions, lung cancer is appropriately the subject of intense clinical investigation and controversy throughout the world
[en] The classic sequence in the pathogenesis of osteoradionecrosis of the jaws has been accepted as radiation, trauma, and infection. This paper challenges this sequence and offers a new one more accurately describing the biochemical and cellular pathology. The clinical data are based on 26 consecutive cases of osteoradionecrosis from which 12 en bloc resection specimens were cultured and stained for microorganisms. Review of the histories and treatments, as well as the microbial assays, indicates that microorganisms play only a contaminant role in osteoradionecrosis and that trauma is only one mechanism of tissue breakdown leading to the condition. The sequence suggested by this study is as follows: (1) radiation, (2) hypoxic-hypocellular-hypovascular tissue, (3) tissue breakdown, and (4) chronic non-healing wound