Medical education in pediatric rheumatology—unique challenges and opportunities

Clinical Rheumatology - Pediatric rheumatology faces workforce shortages in both developed and developing regions of the world resulting in suboptimal care of children with chronic rheumatic...     

Castleman’s disease of the pleura

Castleman’s disease is a rare benign disease of the lymph nodes. Its origin from the pleura is rare. Surgical excision, when feasible, appears to provide good results. We encountered a patient who had the disease arising from the parietal pleura. We present the clinical scenario, investigations, and our management of the patient.     

Benign fibrous histiocytoma of the distal radius with congenital dislocation of the radial head: a case report

Benign fibrous histiocytoma is such a rare tumour that only a few cases have been reported in the literature. A patient with an apparently benign lesion of the distal radius, along with congenital dislocation of the radial head, was presented at St. John's Medical College Hospital in Bangalore, India. Pain was the chief symptom. There were histological features of non-ossifying fibroma in the lesion. Because of its unusual radiological appearance and atypical clinical course, the lesion was diagnosed as fibrous histiocytoma. In this case report, we review similar cases in the literature and discuss an unusual association with congenital dislocation of the radial head.     

Effect of fluoride intoxication on the levels of intestinal antioxidants studied in rats

High concentration of fluorine is noxious to the health of humans and animals. Analysis of fluoride in water samples meant for human consumption in the Vellore District of Tamil Nadu, India, revealed its presence above the permissible limit (4.56 ppm). The present study was aimed to investigate the toxic effects of oral administration of the water sample that contains the highest fluoride content on the status of pathophysiological parameters and lipid peroxidation in experimental rats. A positive control group orally treated with 4.5 ppm of fluoride was also included in the study. The assay of pathophysiological enzymes and histological observations made on the stomach and intestinal tissue have revealed the toxic effects of fluoride intoxication. The observed increase in the levels of thiobarbituric acid reactive substances (TBARS) both in plasma and in intestinal epithelium, with a concomitant decrease in both enzymatic and nonenzymatic antioxidants in the plasma of experimental rats, revealed that the altered antioxidant status during fluoride intoxication may be due to increased free radical generation.     

Interleukin-8 derived from local tissue-resident stromal cells promotes tumor cell invasion

The aim of this study is to evaluate the role of adipose tissue resident stromal cells on tumor cell invasion. Our data show that a subpopulation of adipose tissue derived stromal cells expressing Nestin, NG2, α‐smooth muscle actin and PDGFR‐α migrate toward the cancer cells. Microarray analysis revealed the upregulation of IL‐8 in the migrated cells. We demonstrated that stromal cell derived IL‐8 promote the invasion and the anchorage‐independent growth of cancer cells. We conclude that human breast cancer cells attract a subpopulation of stromal cells that secrete IL‐8 to promote tumor cell invasion in a paracrine fashion. © 2011 Wiley Periodicals, Inc.     

Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors

Background

Carcinoma-associated fibroblasts (CAF) are considered to contribute to tumor growth, invasion and metastasis. However, the cell type of origin remains unknown. Since human adipose tissue derived stem cells (hASCs) are locally adjacent to breast cancer cells and might directly interact with tumor cells, we investigated whether CAFs may originate from hASCs.

Methods

hASCs cultured under different conditions were quantified for the expression of alpha smooth muscle actin. ELISA was performed using the human TGFβ1, SDF-1α and CCL5 Quantikine Kit. The invasion potential of MDAMB231 cancer cells was evaluated using a Boyden chamber with filter inserts coated with Matrigel in 24-well dishes.

Results

We demonstrated that a significant percentage of hASCs differentiated into a CAF-like myofibroblastic phenotype (e.g. expression of alpha smooth muscle actin and tenascin-C) when exposed to conditioned medium from the human breast cancer lines MDAMB231 and MCF7. The conditioned medium from MDAMB231 and MCF7 contains significant amounts of transforming growth factor-beta 1 (TGFβ1) and the differentiation of hASCs towards CAFs is dependent on TGFβ1 signaling via Smad3 in hASCs. The induction of CAFs can be abolished using a neutralizing antibody to TGFβ1 as well as by pretreatment of the hASCs with SB431542, a TGFβ1 receptor kinase inhibitor. Additionally, we found that these hASC-derived CAF-like cells exhibit functional properties of CAFs, including the ability to promote tumor cell invasion in an in vitro invasion assay, as well as increased expression of stromal-cell derived factor 1 (SDF-1) and CCL5.

Conclusion

Our data suggest that hASCs are a source of CAFs which play an important role in the tumor invasion.     

Autoantibody cluster analysis in juvenile lupus nephritis

Clinical Rheumatology - Demographics, clinical features, and biomarkers do not consistently anticipate risk of end-stage renal disease (ESRD) in juvenile lupus nephritis (LN). Here, the existence...     

Giant solitary fibrous tumour of the pleura

Solitary fibrous tumour of the pleura is a rare primary pleural neoplasm. These tumours are usually asymptomatic and are incidentally detected. Majority of these neoplasms are benign and surgical excision provides excellent results. With the widespread use of imaging and better diagnostic criteria, this tumour is likely to be detected more frequently. We encountered a patient with a giant solitary fibrous tumour of the pleura. In this report, we describe the case of a patient with a giant solitary fibrous tumour of the pleura, review the literature and present the details of management of this patient.     

Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cells

Epithelial-mesenchymal transition (EMT) generates tumor cells with stem cell properties. The aim of our study was to investigate the effects of adipose tissue-derived stem cells (ASCs) on EMT of cancer cells and to further investigate the mechanisms involved. We demonstrate that conditioned medium from ASCs induces breast cancer cells (4T1) to express mesenchymal markers such as fibronectin, alpha smooth muscle actin and vimentin. Flow cytometry analyses show that ASC-conditioned medium promotes the expansion of CD44high/CD24low cancer stem cells. Soft agar assays using T47D, BT474 and MCF-7 breast cancer cells reveals that ASC conditioned medium promotes the anchorage-independent growth of cancer cells. These effects were inhibited by a neutralizing antibody against platelet-derived growth factor-D (PDGF-D). Furthermore, PDGF-D treated breast cancer cells grow faster in a mouse model, and this effect could be neutralized by a PDGF antibody. In conclusion, our data show that tissue-resident stem cells interact with the cancer microenvironment via PDGF-D, induce EMT in the cancer cells in a paracrine fashion, thereby increasing the number of cancer stem cells and increase tumor growth in a PDGF dependent manner. Our findings shed new light on mechanisms where local tissue-resident stem cells are able to promote the growth of breast cancer cells. Possibly this could open up a novel selective therapeutic strategy targeting EMT pathways and the specific communication between tissue-resident normal stem cell and cancer stem cells, assuming that the blockage of PDGF-D pathways is critical for tumor growth but would not affect normal tissue homeostasis.     

Tuberculosis of knee joint mimicking giant cell tumor – A case report

A 50-year-old woman presented with pain, swelling, and reduced range of motion of right knee joint since one year. Radiograph of knee joint revealed eccentric, expansile, geographic lytic lesion on the medial epiphyseal region of tibia mimicking giant cell tumor (GCT). She underwent minimally invasive biopsy, which was positive for acid-fast bacilli and revealed necrotizing chronic granulomatous lesion, diagnostic of tuberculosis (TB). This case emphasizes to consider tuberculosis arthritis as differential diagnosis when a case of destructive giant cell tumor is encountered.