Objective: Striatins(STRNs) family, which contains three multi-domain scaffolding proteins, are cornerstones of the striatins interacting phosphatase and kinase(STRIPAK) complex. Although the role of the STRIPAK compl...Objective: Striatins(STRNs) family, which contains three multi-domain scaffolding proteins, are cornerstones of the striatins interacting phosphatase and kinase(STRIPAK) complex. Although the role of the STRIPAK complex in cancer has become recognized in recent years, its clinical significance in breast cancer has not been fully established.Methods: Using a freshly frozen breast cancer tissue cohort containing both cancerous and adjacent normal mammary tissues, we quantitatively evaluated the transcript-level expression of all members within the STRIPAK complex along with some key interacting and regulatory proteins of STRNs. The expression profile of each molecule and the integrated pattern of the complex members were assessed against the clinical-pathological factors of the patients. The Cancer Genome Atlas(TCGA) dataset was used to evaluate the breast cancer patients’ response to chemotherapies. Four human breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, and SKBR-3, were subsequently adopted for in vitro work.Results: Here we found that high-level expressions of STRIP2, calmodulin, CCM3, MINK1 and SLMAP were respectively associated with shorter overall survival(OS) of patients. Although the similar pattern observed for STRN3, STRN4 and a contrary pattern observed for PPP2CA, PPP2CB and PPPR1A were not significant, the integrated expression profile of STRNs group and PPP2 group members constitutes a highly significant prognostic indicator for OS [P<0.001, hazard ratio(HR)=2.04, 95% confidence interval(95% CI), 1.36-3.07] and disease-free survival(DFS)(P=0.003, HR=1.40, 95% CI, 1.12-1.75). Reduced expression of STRN3 has an influence on the biological functions including adhesiveness and migration. In line with our clinical findings, the breast cancer cells responded to STRN3 knockdown with changes in their chemo-sensitivity, of which the response is also breast cancer subtype dependent.Conclusions: Our results suggest a possible role of the STRIPAK complex in breast cancer development and prognosis. Among the members, the expression profile of STRN3 presents a valuable factor for assessing patients’ responses to drug treatment.展开更多
Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Method...Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Methods: In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ. Results: Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73% ) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events. Limitations: Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy. Conclusions: In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.展开更多
AIM To determine whether tissue identified at the joint line was actually remnant "meniscal" scar tissue or not. METHODS Nine patients undergoing revision knee surgery following informed consent had meniscal...AIM To determine whether tissue identified at the joint line was actually remnant "meniscal" scar tissue or not. METHODS Nine patients undergoing revision knee surgery following informed consent had meniscal scar tissue sent to the histology department for analyses. All revisions were performed where joint line had been raised or lowered at earlier surgery. Although preoperative radiographic evaluations suggested that the joint line had been altered, intraoperatively there was scar tissue at the level of the recreated joint line. This scar tissue has traditionally been described as meniscal scar, and to identify the origins of this tissue, samples were sent for histological analyses. The tissue samples were stored in formalin, and embedded and sectioned before undergoing histochemical staining. All samples underwent macroscopic and microscopic examination by a histopathologist who was blind to the study aims. The specific features that were examined included tissue organisation, surface and central composition, cellular distribution including histiocytes, nuclear ratio and vasculature. Atypical and malignant features, inflammation and degeneration were specifically looked for. A statistical review of the study was performed by a biomedical statistician.RESULTS The histological findings for the nine patients showingthe macroscopic and microscopic findings, and the conclusion are outlined in a Table. The histological analyses were reviewed to determine whether the tissue samples were likely to be meniscal scar tissue. The response was yes(2, 22%), no(6, 67%) and maybe(1,11%) based on the conclusions. The results were "yes"when on macroscopy, firm cream tissue was identified.In these two "yes" samples, microscopic analyses showed organised fibrous tissue with focal degenerative areas with laminated pattern associated with histiocytes peripherally but no inflammation. The "no" samples were assessed macroscopically and microscopically and were deemed to have appearances representing fibrous synovial tissue and features in keeping with degenerate scar tissue or connective tissue. One sample was indeterminate and microscopically contained fibrocollagenous tissue with synovial hyperplasia. It also contained some degenerate hyalinised tissue that may represent cartilage, but the appearances were not specific. CONCLUSION Based on our pilot study, we recommend reliance on a number of markers to identify the joint line as outlined above, and to exercise caution in using the "meniscal"scar.展开更多
Diagnosis of abuse in children with internal abdominal injury is difficult because of limited published work. We aimed to ascertain the incidence of abdominal injury due to abuse in children age 0- 14 years. 20 childr...Diagnosis of abuse in children with internal abdominal injury is difficult because of limited published work. We aimed to ascertain the incidence of abdominal injury due to abuse in children age 0- 14 years. 20 children (identified via the British Paediatric Surveillance Unit) had abdominal injuries due to abuse and 164 (identified via the Trauma Audit and Research Network) had injuries to the abdomen due to accident (112 by road-traffic accidents, 52 by falls). 16 abused children were younger than 5 years. Incidence of abdominal injury due to abuse was 2.33 cases per million children per year (95% CI 1.43- 3.78) in children younger than 5 years. Six abused children died. 11 abused children had an injury to the gut (ten small bowel)- compared with five (all age > 5 years) who were injured by a fall (relative risk 5.72 [95% CI 2.27- 14.4]; p=0.0002). We have shown that small-bowel injuries can arise accidentally as a result of falls and road-traffic accidents but they are significantly more common in abused children. Therefore, injuries to the small bowel in young children need special consideration, particularly if a minor fall is the explanation.展开更多
基金supported by the Cardiff University China Medical Scholarship。
文摘Objective: Striatins(STRNs) family, which contains three multi-domain scaffolding proteins, are cornerstones of the striatins interacting phosphatase and kinase(STRIPAK) complex. Although the role of the STRIPAK complex in cancer has become recognized in recent years, its clinical significance in breast cancer has not been fully established.Methods: Using a freshly frozen breast cancer tissue cohort containing both cancerous and adjacent normal mammary tissues, we quantitatively evaluated the transcript-level expression of all members within the STRIPAK complex along with some key interacting and regulatory proteins of STRNs. The expression profile of each molecule and the integrated pattern of the complex members were assessed against the clinical-pathological factors of the patients. The Cancer Genome Atlas(TCGA) dataset was used to evaluate the breast cancer patients’ response to chemotherapies. Four human breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, and SKBR-3, were subsequently adopted for in vitro work.Results: Here we found that high-level expressions of STRIP2, calmodulin, CCM3, MINK1 and SLMAP were respectively associated with shorter overall survival(OS) of patients. Although the similar pattern observed for STRN3, STRN4 and a contrary pattern observed for PPP2CA, PPP2CB and PPPR1A were not significant, the integrated expression profile of STRNs group and PPP2 group members constitutes a highly significant prognostic indicator for OS [P<0.001, hazard ratio(HR)=2.04, 95% confidence interval(95% CI), 1.36-3.07] and disease-free survival(DFS)(P=0.003, HR=1.40, 95% CI, 1.12-1.75). Reduced expression of STRN3 has an influence on the biological functions including adhesiveness and migration. In line with our clinical findings, the breast cancer cells responded to STRN3 knockdown with changes in their chemo-sensitivity, of which the response is also breast cancer subtype dependent.Conclusions: Our results suggest a possible role of the STRIPAK complex in breast cancer development and prognosis. Among the members, the expression profile of STRN3 presents a valuable factor for assessing patients’ responses to drug treatment.
文摘Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Methods: In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ. Results: Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73% ) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events. Limitations: Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy. Conclusions: In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.
文摘AIM To determine whether tissue identified at the joint line was actually remnant "meniscal" scar tissue or not. METHODS Nine patients undergoing revision knee surgery following informed consent had meniscal scar tissue sent to the histology department for analyses. All revisions were performed where joint line had been raised or lowered at earlier surgery. Although preoperative radiographic evaluations suggested that the joint line had been altered, intraoperatively there was scar tissue at the level of the recreated joint line. This scar tissue has traditionally been described as meniscal scar, and to identify the origins of this tissue, samples were sent for histological analyses. The tissue samples were stored in formalin, and embedded and sectioned before undergoing histochemical staining. All samples underwent macroscopic and microscopic examination by a histopathologist who was blind to the study aims. The specific features that were examined included tissue organisation, surface and central composition, cellular distribution including histiocytes, nuclear ratio and vasculature. Atypical and malignant features, inflammation and degeneration were specifically looked for. A statistical review of the study was performed by a biomedical statistician.RESULTS The histological findings for the nine patients showingthe macroscopic and microscopic findings, and the conclusion are outlined in a Table. The histological analyses were reviewed to determine whether the tissue samples were likely to be meniscal scar tissue. The response was yes(2, 22%), no(6, 67%) and maybe(1,11%) based on the conclusions. The results were "yes"when on macroscopy, firm cream tissue was identified.In these two "yes" samples, microscopic analyses showed organised fibrous tissue with focal degenerative areas with laminated pattern associated with histiocytes peripherally but no inflammation. The "no" samples were assessed macroscopically and microscopically and were deemed to have appearances representing fibrous synovial tissue and features in keeping with degenerate scar tissue or connective tissue. One sample was indeterminate and microscopically contained fibrocollagenous tissue with synovial hyperplasia. It also contained some degenerate hyalinised tissue that may represent cartilage, but the appearances were not specific. CONCLUSION Based on our pilot study, we recommend reliance on a number of markers to identify the joint line as outlined above, and to exercise caution in using the "meniscal"scar.
文摘Diagnosis of abuse in children with internal abdominal injury is difficult because of limited published work. We aimed to ascertain the incidence of abdominal injury due to abuse in children age 0- 14 years. 20 children (identified via the British Paediatric Surveillance Unit) had abdominal injuries due to abuse and 164 (identified via the Trauma Audit and Research Network) had injuries to the abdomen due to accident (112 by road-traffic accidents, 52 by falls). 16 abused children were younger than 5 years. Incidence of abdominal injury due to abuse was 2.33 cases per million children per year (95% CI 1.43- 3.78) in children younger than 5 years. Six abused children died. 11 abused children had an injury to the gut (ten small bowel)- compared with five (all age > 5 years) who were injured by a fall (relative risk 5.72 [95% CI 2.27- 14.4]; p=0.0002). We have shown that small-bowel injuries can arise accidentally as a result of falls and road-traffic accidents but they are significantly more common in abused children. Therefore, injuries to the small bowel in young children need special consideration, particularly if a minor fall is the explanation.
