Cronkhite-Canada syndrome associated with rib fractures: a case report

<p>Abstract</p> <p>Background</p> <p>Cronkhite-Canada syndrome (CCS) is a rare multiple gastrointestinal polyposis. Up till now, many complications of CCS have been reported in the literature, but rib fracture is not included.</p> <p>Case Presentation</p> <p>We report a case of a 58-year-old man who was admitted to our hospital with a 6-month history of frequent diarrhea, intermittent hematochezia and a weight loss of 13 kg. On admission, physical examination revealed alopecia of the scalp, hyperpigmentation of the hands and soles, and dystrophy of the fingernails. Laboratory data revealed hypocalcaemia and hypoproteinemia. Esophagogastroduodenoscopy, video capsule endoscopy and colonoscopy revealed various sizes of generalized gastrointestinal polyps. Histological examination of the biopsy specimens obtained from the stomach and the colon showed adenomatous polyp and inflammatory polyp respectively. Thus, a diagnosis of CCS was made. After treatment with corticosteroids for 24 days and nutritional support for two months, his clinical condition improved. Two months later, he was admitted to our hospital for the second time with frequent diarrhea and weight loss. The chest radiography revealed fractures of the left sixth and seventh ribs. Examinations, including emission computed tomography, bone densitometry test, and other serum parameters, were performed, but could not identify the definite etiology of the rib fractures. One month later, the patient suffered from aggravating multiple rib fractures due to the ineffective treatment, persistent hypocalcaemia and malnutrition.</p> <p>Conclusions</p> <p>This is the first case of a CCS patient with multiple rib fractures. Although the association between CCS and multiple rib fractures in this case remains uncertain, we presume that persistent hypocalcaemia and malnutrition contribute to this situation, or at least aggravate this rare complication. Besides, since prolonged corticosteroid therapy will result in an increased risk of osteoporotic fracture, CCS patients who accept corticosteroid therapy could be potential victims of rib fracture.</p

Comparison of the efficacy and safety of S-1-based and capecitabine-based regimens in gastrointestinal cancer: a meta-analysis.

PurposeOral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers.MethodsEligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events.ResultsA total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78-1.09, P = 0.360), OS (HR 1.01, 95% CI 0.84-1.21, P = 0.949), ORR (HR 1.04, 95% CI 0.87-1.25, P = 0.683) and DCR (HR 1.02, 95% CI 0.94-1.10, P = 0.639). There was also no significant difference in toxicity between regimens other than mild more hand-foot syndrome in capecitabine-based regimens.ConclusionBoth the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers

Curcumin derivative C212 inhibits Hsp90 and eliminates both growing and quiescent leukemia cells in deep dormancy

Background: Relapsed leukemia following initial therapeutic response and remission is difficult to treat and causes high patient mortality. Leukemia relapse is due to residual quiescent leukemia cells that escape conventional therapies and later reemerge. Eliminating not only growing but quiescent leukemia cells is critical to effectively treating leukemia and preventing its recurrence. Such dual targeting therapeutic agents, however, are lacking in the clinic. To start tackling this problem, encouraged by the promising anticancer effects of a set of curcumin derivatives in our earlier studies, we examined in this work the effects of a 4-arylmethyl curcumin derivative (C212) in eliminating both growing and quiescent leukemia cells. Methods: We analyzed the effects of C212 on the growth and viability of growing and quiescent leukemia cells using MTS, apoptosis, cell cycle and cell tracking assays. The effects of C212 on the quiescence depth of leukemia cells were measured using EdU incorporation assay upon growth stimulation. The mechanisms of C212-induced apoptosis and deep dormancy, particularly associated with its inhibition of Hsp90 activity, were studied using molecular docking, protein aggregation assay, and Western blot of client proteins. Results: C212, on the one hand, inhibits growing leukemia cells at a higher efficacy than curcumin by inducing apoptosis and G2/M accumulation; it, on the other hand, eliminates quiescent leukemia cells that are resistant to conventional treatments. Furthermore, C212 drives leukemia cells into and kills them at deep quiescence. Lastly, we show that C212 induces apoptosis and drives cells into deep dormancy at least partially by binding to and inhibiting Hsp90, leading to client protein degradation and protein aggregation. Conclusion: C212 effectively eliminates both growing and quiescent leukemia cells by inhibiting Hsp90. The property of C212 to kill quiescent leukemia cells in deep dormancy avoids the risk associated with awaking therapy-resistant subpopulation of quiescent leukemia cells during treatments, which may lead to the development of novel therapies against leukemia relapse.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Impaired Function of CD5+CD19+CD1dhi B10 Cells on IgE Secretion in an Atopic Dermatitis-Like Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease in which the pathogenic mechanism is complicated and not completely understood. Reports on the role of regulated cells in AD have recently evolved to regulate B cells, which may play a role in allergic inflammation as well. In the present study, we examined the frequency and regulatory function of CD5+CD19+CD1dhi B10 cells in an AD-like mouse model. Our results showed that the percentage of CD5+CD19+CD1dhi B10 cells increased while the frequency of IL-10-producing B cells in CD19+B cells decreased in the mice of AD group. Moreover, no difference in the percentage of B10pro + B10 cells was observed between the AD and control groups. Strikingly, B10 cells from control mice effectively inhibited IgE secretion, whereas the suppressive function of B10 cells from the AD mice was significantly decreased, which was similar to that observed in the group without B10. Altogether, these results suggest that the number of IL-10-producing B cells decreased in the AD group and these cells showed a defective regulatory function on IgE secretion

Begg's funnel plot of publication bias test.

<p>(A) PFS; (B) OS. Each point represents a separate study for the indicated association. Log (OR), natural logarithm of OR. Horizontal line, mean effect size.</p

Influence of CD5⁺CD19⁺CD1d^hi B10 cells on IgE production.

<p>B10 cells were sorted from the spleen of AD mice (n = 5) and control mice (n = 5) by flow cytometry. The PBMCs from normal mice and B10 cells from control or AD mice were cultured with LPS (10 μg/mL), PMA (50 ng/mL), and iono (500 ng/mL) for 72h,then the IgElevels were determined in the supernatants by ELISA.PBMCs without B10 cell wereused as a negative control. No differences in IgE levels were observed in the AD and negative control groups, and both groups showed significantly higher IgElevel than that observed in the control group. Data are expressed as mean ± SEM. **P < 0.01, as analyzed by one-way ANOVA, followed by Tukey multiple-comparison test.</p

Fixed-effects model of hazard ratio (95% confidence interval) of PFS associated with S-1-based therapy compared with capecitabine-based therapy.

<p>Fixed-effects model of hazard ratio (95% confidence interval) of PFS associated with S-1-based therapy compared with capecitabine-based therapy.</p