The aim of this study was to evaluate the diagnostic value of Dsg1 and 3 enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pemphigus. Thirty-six patients with pemphigus were enrolled. The diagnosis was confirmed by histopathology and direct immunofluorescence (DIF). Autoantibodies against Dsg1, and Dsg3 were assayed, by ELISA, in serum of pemphigus patients. In pemphigus vulgaris (PV), anti-Dsg1 and anti-Dsg 3 antibodies titre were raised above the cut off value in 88.5% and 96.1% of patients respectively. Dsg-3 was more sensitive than Dsg-1(96.2% versus 88.5%) while both have the same specificity 95%. In PF and PH, the only anti-Dsg-1 level was raised in all cases (100%). Conclusion: In PV Dsg-3 was more sensitive than Dsg-1while in pemphigus foliaceous and pemphigus herpetiformis, only anti-Dsg-1 was detected in all cases (100%). Both anti-Dsg1Ab and anti-Dsg3Ab ELISA values are correlated with the disease activity.

The aim of this study was to evaluate the diagnostic value of Dsg1 and 3 enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pemphigus. Thirty-six patients with pemphigus were enrolled. The diagnosis was confirmed by histopathology and direct immunofluorescence (DIF). Autoantibodies against Dsg1, and Dsg3 were assayed, by ELISA, in serum of pemphigus patients. In pemphigus vulgaris (PV), anti-Dsg1 and anti-Dsg 3 antibodies titre were raised above the cut off value in 88.5% and 96.1% of patients respectively. Dsg-3 was more sensitive than Dsg-1(96.2% versus 88.5%) while both have the same specificity 95%. In PF and PH, the only anti-Dsg-1 level was raised in all cases (100%). Conclusion: In PV Dsg-3 was more sensitive than Dsg-1while in pemphigus foliaceous and pemphigus herpetiformis, only anti-Dsg-1 was detected in all cases (100%). Both anti-Dsg1Ab and anti-Dsg3Ab ELISA values are correlated with the disease activity.

While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1–Cullin-1–Skp2 (SCFSkp2) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCFSkp2 activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138+ cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138+ cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCFSkp2 complex, stabilized p27 and increased the number of annexin-V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCFSkp2 inhibitors to treat BTZ resistant disease.

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BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti- Mu¨ llerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Mu¨ llerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Mu¨ llerian hormone concentration after ovarian cystectomy (weighted mean difference, e1.14 ng/mL; 95% confidence interval, e1.36 to e0.92; I2 ¼ 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti- Mu¨ llerian hormone assay and studies using IOT anti-Mu¨ llerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti- Mu¨ llerian hormone (weighted mean difference, e1.44 [95% confidence interval, e1.71 to e1.1; I2 ¼ 0%], e0.88 [95% confidence interval, e1.71 to e0.04; I2 ¼ 0%], and e1.56 [95% confidence interval, e2.44 to e0.69; I2 ¼ 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Mu¨ llerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Mu¨ llerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.

BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti- Mu¨ llerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Mu¨ llerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Mu¨ llerian hormone concentration after ovarian cystectomy (weighted mean difference, e1.14 ng/mL; 95% confidence interval, e1.36 to e0.92; I2 ¼ 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti- Mu¨ llerian hormone assay and studies using IOT anti-Mu¨ llerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti- Mu¨ llerian hormone (weighted mean difference, e1.44 [95% confidence interval, e1.71 to e1.1; I2 ¼ 0%], e0.88 [95% confidence interval, e1.71 to e0.04; I2 ¼ 0%], and e1.56 [95% confidence interval, e2.44 to e0.69; I2 ¼ 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Mu¨ llerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Mu¨ llerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.