Mechanism of action of a tyrphostin, 3,4-dihydroxy-α-cyanothiocinnamamide, in breast cancer cell growth inhibition involves the suppression of cyclin B1 and the functional activity of cyclin B1/p34cdc2 complex

Tyrphostins are a group of compounds specifically targeted for the inhibition of tyrosine phosphorylation in signal transduction pathways. We studied the effects of a tyrphostin, 3,4-dihydroxy--cyanothiocinnamamide (tyrphostin-47), on hormone-responsive MCF-7 and hormone-unresponsive MCF-7-5C cell growth by DNA analysis for a period of 10 days. The growth of both cell lines was inhibited by this drug at 50 and 100 µM concentrations. Flow cytometric analysis showed that tyrphostin treatment caused a significant delay in the progression of MCF-7 cells through Gl and S phases of the cell cycle. The level of cyclin B1, a component of the mitosis promoting factor (MPF), was reduced by 90% in the presence of 100 µM tyrphostin. The other component of MPF, p34cdc2 kinase, was not affected; however, its functional activity was dramatically reduced, as determined by histone H1 phosphorylation assay. In contrast, G1 cyclins (D1 and E) and tyrosine kinase activity were not markedly affected by tyrphostin-47, as determined by Western immunoblot detection with specific antibodies. Our results suggest that a possible mechanism of tyrphostin action in breast cancer cells might involve the suppression of cyclin B1 and inhibition of the functional activity of cyclin B1/p34cdc2 complex. Our data indicate that the cell cycle machinery might be a target for developing novel drugs for breast cancer.     

Aneurysmal bone cyst of the extremities. Factors related to local recurrence after curettage with a high-speed burr

BACKGROUND: Aneurysmal bone cyst is a benign, locally destructive lesion of bone. The rates of local recurrence after curettage have varied widely. Therefore, we performed a retrospective study of patients who had had an aneurysmal bone cyst in order to identify the rate of local recurrence and the prognostic factors related to local recurrence after use of contemporary methods of curettage with a high-speed burr. METHODS: We reviewed the cases of forty patients who had been managed by the same surgeon for an aneurysmal bone cyst, as diagnosed on the basis of the latest pathological review, between January 1, 1976, and December 31, 1993. The patients were evaluated with regard to age, gender, the duration and type of symptoms, the presence or absence of pathological fracture, the status of the growth plate, the bone and part of the bone that were involved, the type of operative procedure, the outcome, the radiographic stage, the findings on magnetic resonance imaging and computerized tomography (when it became available) and on bone scintigraphy, and histological parameters. The median duration of follow-up was eighty-seven months (range, fifteen to 267 months). According to the criteria of Enneking, no patient had a stage-1 lesion (one with a surrounding rim of cortical bone), twenty-four had a stage-2 lesion (one with a clearly defined border but no cortical bone), and sixteen had a stage-3 lesion (one with no clearly defined border). RESULTS: Of the forty patients, thirty-four had curettage with use of a high-speed burr. Of these thirty-four, twenty-two had filling of the defect with a cancellous autogenous graft; four, with a cancellous allograft; and three, with polymethylmethacrylate. In five patients, no material was put into the defect. The remaining six patients had resection through the margin of the lesion. Four (12 percent) of the thirty-four patients who had curettage had a local recurrence. No patient who had an excision through the margin of the lesion had a local recurrence. All local recurrences were in skeletally immature girls who were three, four, ten, and eleven years old. Univariate analysis with use of the chi-square, Fisher exact, and Wilcoxon log-rank tests showed that local recurrence was associated only with a young age (p = 0.0036) and open growth plates (p = 0.039). All local recurrences occurred within two years postoperatively, at two, seven, nine, and twenty-four months, and all were treated successfully with a second operation. CONCLUSIONS: Rates of local control of almost 90 percent can be achieved with thorough curettage with use of a mechanical burr and without use of liquid nitrogen, phenol, or other adjuvants in patients who have an aneurysmal bone cyst of an extremity. A young age and open growth plates are associated with an increased risk of local recurrence.     

Osteochondroma of the first rib presenting as a prominent clavicle

We describe and discuss two patients with osteochondromas of the first rib which presented as prominence of the medial end of the clavicle.     

Short-term effects of mobilisation with movement in patients with post-traumatic stiffness of the knee joint

Background

Mobilisation with movement treatment techniques have been used to increase the range of motion following pathologies associated with shoulder, elbow and ankle joints. Lack of posterior tibial glide and reflex muscle inhibition are common physical impairments in individuals with post-traumatic stiffness of the knee joint. Current evidence is lacking for the benefits of mobilisation with movement treatment techniques for the knee joint disorders.

Limberg Flap for Sacrococcygeal Pilonidal Sinus a Safe and Sound Procedure

Sacrococcygeal pilonidal sinus (SC-PSD) is an acquired condition usually seen in young adults especially males. This prospective study has been performed to determine effects of the Limberg flap rotation surgery for sacrococcygeal pilonidal sinus, its feasibility to the patients, their compliance, and outcomes such as wound infection, postoperative pain relief, recurrence rates, and return to work. A total of 30 patients were operated by the same two surgeons from January 2009 to June 2011, including both primary and recurrent diseases, and patients with previous incision and drainage done for the pilonidal abscess. All patients successfully underwent surgery, with very minimal postoperative pain, stayed in hospital for average 5 days, returned to work after 3 weeks, with 3 patients having flap edema, 2 having flap necrosis, and no recurrences so far. Patients with flap edema and flap necrosis took 2–3 weeks to heal with regular dressing and antibiotic usage. Limberg flap for sacrococcygeal pilonidal sinus was found very useful and sound in terms of postoperative pain, infection rates, and early return to work with almost nil recurrences.     

Periodontal findings in patients with oral submucous fibrosis and comet assay of affected gingival epithelial cells

Background: Oral submucous fibrosis (OSF) involves large sections of population and is related to certain chewing practices that involve direct exposure of the gingiva to noxious chemicals and additives. The impact of such practices, although studied extensively in relation to the cheek mucosa, is not elucidated as far as gingival tissues are concerned. The possible DNA damage on affected gingiva is also one of the objectives of the present study. Methods: One hundred cases of individuals with OSF and 89 without OSF were examined for periodontal parameters and compared. Biopsies of gingival tissue from both categories were examined with conventional hematoxylin and eosin staining for epithelial, connective tissue, and inflammatory changes. Comet assay of epithelial cells obtained from scraping the gingival surface of both patients with OSF and control individuals was performed . Results: Patients with OSF had poorer oral hygiene and greater loss of attachment, probing depth, and recession compared with controls. Significant histopathologic changes in the form of loss of rete ridges with gingival epithelium reduced to a flattened surface was observed. All the patients with OSF showed comet cells in larger numbers. The controls also showed comet cells but in fewer numbers, and the number of individuals showing comet cells was significantly less. Conclusion: OSF showed significant changes in affected gingiva, and the presence of comet cells in all the patients with OSF is a significant indicator of possible pathognomonic developments.