Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development

Introduction  

Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascade that regulates cell growth and survival. Interestingly, mammary-specific expression of either one of these proteins has been shown to promote mammary tumorigenesis. In light of our recent findings and to investigate the potential interaction between Wnt and ILK proteins during mammary tumor formation and progression, we established a transgenic mouse model that expresses both Wnt and ILK in mammary epithelial cells.     

Efficacy and Safety of Busulfan‐Based Conditioning Regimens for Multiple Myeloma

Multiple myeloma is a malignancy of B cells characterized by accumulation of abnormal plasma cells in the bone marrow. In the past 20 years, the use of high‐dose therapies and novel agents has resulted in significant and meaningful improvements in survival. Autologous stem cell transplantation (auto‐SCT) following a high‐dose melphalan‐conditioning regimen represents the standard of care for younger patients as well as older patients with a good performance status. A number of strategies have been proposed to improve the outcome of auto‐SCTs, including the incorporation of new agents such as thalidomide, lenalidomide, and bortezomib into the induction regimen administered before auto‐SCT; the administration of maintenance therapy after auto‐SCT; the incorporation of novel agents into chemotherapeutic regimens after transplantation as consolidation therapy; and the use of reduced‐intensity allogeneic transplantation after an initial autograft. Although these approaches have demonstrated some success in improving responses after auto‐SCT, none of these strategies are curative. An additional strategy to improve outcomes after auto‐SCT is to enhance the immediate pretransplant conditioning regimens by either increasing the dose of melphalan or by incorporating novel agents, such as busulfan. This literature review focuses on the efficacy and safety of busulfan‐based conditioning regimens for auto‐SCT in patients with multiple myeloma.     

Patients’ perception toward various dental treatments provided in the internship program

Objectives:

To evaluate patients’ perception regarding treatment and environment in the interns’ clinic at a university dentistry clinic.

Methods:

This cross-sectional study was conducted between July 2012 to May 2013 at the College of Dentistry, University of Dammam, Dammam, Kingdom of Saudi Arabia. A self-directed questionnaire was distributed to 220 randomly selected patients, and the response rate was approximately 68%. Patients’ were asked regarding dentists’ behavior, treatment, and clinical environment along with their demographics, and socioeconomic status.

Results:

Out of the 220 randomly selected patients, 150 participated in the study. The average age of a respondent was 32.5 years (±14.5), 89 of the 150 participants were Saudi nationals. Collectively, 86% were satisfied with the doctors’ behavior, and approximately 94% responded that the dentist listens to their concerns. Most (83%) were satisfied with the treatment plan provided by the interns.

Conclusion:

The findings in this study showed that more than 80% of the participants were satisfied with the quality of treatment and clinical environment. The dissatisfaction rate was minimal (13%) and for this reason, it is difficult to establish the factors for patients dissatisfaction.Evaluation of patients’ satisfaction and meeting their expectations helps to quantify quality of services provided to them. Identifying patient expectations by obtaining their feedback helps to improve the quality of services provided in the clinics. In an academic institution, it is crucial to evaluate quality of care provided to patients. An increase in the number of satisfied patients increases patient cooperation, and motivation.1 Patients’ attitude toward health care experience develops over time, and can be influenced by numerous factors.2 Overall satisfaction is also influenced by the age of a patient, and when satisfaction was related to communication, young male participants produced a higher satisfaction score than other respondents.3,4 Furthermore, a direct relation was found between education level and patients’ satisfaction, and low income group consistently produced low satisfaction scores.5,6 However, features such as neatness, comfort of seating, magazine selection, and background music of the clinic facilities have been reported to influence patient perceptions.7 The College of Dentistry in the University of Dammam facilitates its students by providing them a one year internship program. After finishing course work, students must serve one year in the clinics under the supervision of a faculty member to enhance their skills. The aim of this study was to evaluate patients who visited the interns’ clinics regarding treatment they received, and their satisfaction with the treatment, and clinical environment.     

Thyroid dermopathy: an underrecognized cause of leg edema

Leg edema is a common clinical problem and the differential diagnosis is extensive. We present 4 patients in whom thyroid dermopathy was the cause of leg edema. Examination of the eyes and the nature of the edema were clues to the diagnosis of thyroid dermopathy. Clinical signs should be documented and analysis of skin biopsy specimens should be performed in patients suspected to have thyroid dermopathy.     

Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH(2)- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival.     

Shifting balance from neurodegeneration to regeneration of the brain： a novel therapeutic approach to Alzheimer＇s disease and related neurodegenerative conditions

<正>Neurodegeneration is one of the biggest public health problems in modern society.Age-associated neurodegeneration,which is accelerated several-fold in Alzheimer’s disease(AD)alone,is not only an enormous social and economic burden to the affected individuals and their families,but is also a great scientific challenge.