FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.

Oncogene Moesin plays critical role in initiation, progression, and metastasis of multiple cancers. It exerts oncogenic activity due to its high-level expression as well as posttranslational modification in cancer. However, factors responsible for its high-level expression remain elusive. In this study, we identified positive as well as negative regulators of Moesin. Our study reveals that Moesin is a cellular target of F-box protein FBXW2. We showed that FBXW2 suppresses breast cancer progression through directing proteasomal degradation of Moesin. In contrast, AKT kinase plays an important role in oncogenic function of Moesin by protecting it from FBXW2-mediated proteasomal degradation. Mechanistically, AKT phosphorylates Moesin at Thr-558 and thereby prevents its degradation by FBXW2 via weakening the association between FBXW2 and Moesin. Further, accumulated Moesin prevents FBXW2-mediated degradation of oncogene SKP2, showing that Moesin functions as an upstream regulator of oncogene SKP2. In turn, SKP2 stabilizes Moesin by directing its non-degradable form of polyubiquitination and therefore AKT-Moesin-SKP2 oncogenic axis plays crucial role in breast cancer progression. Collectively, our study reveals that FBXW2 functions as a tumor suppressor in breast cancer by restricting AKT-Moesin-SKP2 axis. Thus, AKT-Moesin-SKP2 axis may be explored for the development of therapeutics for cancer treatment.

A comparative analysis of features and outcome of breast cancer in younger versus older women: A single center experience from Eastern Indian subcontinent.

Purpose: Globally, breast cancer is the leading malignancy in females. Indeed, Asian cohorts show prevalence of breast cancer among women with ages below 40 years. Moreover, these younger cases are globally characterized by poorer prognostic features as well as survival outcomes, than older sufferers with ages above 40 years. Despite this, comparative analyses between older and younger cohorts are sparse from India, where data from the country's eastern part falls shortest. This study attempted a comprehensive analysis of breast cancer between these two cohorts representing the Eastern Indian subcontinent. Methods: Documenting retrospective case-files registered between 2010 and 2015, 394 cases of younger (<40 years) and 1250 older (≥40 years) sufferers of primary breast cancer were noted. The relevant features and follow-up information were also retrieved. Kaplan-Meier analyses were performed to evaluate the survival outcome. Results: The data, in general, revealed a high percentage of younger sufferers from Eastern Indian regions. Moreover, this younger cohort showed poor survival. Among the younger cohort, cases with poor pathological features (triple negative, node-positive, grade III) were proportionately higher than the older cohort. Indeed, survival among these categories scored significantly low, compared to the older cohort. Conclusion: This Eastern Indian subcontinental data matched the analyses from other parts of India as well as Asian data and clearly showed the prevalence of younger sufferers of breast cancer with poor clinico-pathological features and survival outcomes. Impact: Analyzing age-based features and outcomes from Eastern India, this study provides data in supplementing Indian and Asian scenarios of breast cancer.

Ganglion Cyst of Knee from Hoffa's Fat Pad Protruding Anterolaterally Through Retinacular Rent: A Case Report.

INTRODUCTION: Intra-articular ganglion cysts of the knee joint are rare occurrences. They are usually encountered as incidental findings in magnetic resonance imaging (MRI), or in arthroscopy. They may originate from both the cruciate ligaments and the menisci, from the popliteus tendon and alar folds, infrapatellar fat pad of Hoffa, and subchondral bone cysts. Those arising from the Hoffa's fat pad, usually present as palpable mass at anterior aspect of the knee joint. We report a case of intraarticular ganglion cyst of knee arising from the infrapatellar fat pad and protruding anterolaterally through retinacular rent into the subcutaneous plane. CASE REPORT: A 19-year-old young man, presented with a painless gradually increasing swelling at the anterior aspect of left knee of 9 months duration. MRI scan revealed a multilobulated, cyst with septations within the anterior aspect of the knee joint, just inferolateral to the patella, with deep extension into the infrapatellar fat pad, and superficial extension into the subcutaneous space across the retinaculum. After diagnostic arthroscopy, we performed an open excision of the cystic mass and confirmed the retinacular rent pre-operatively. CONCLUSION: Arthroscopic resection and debridement is the gold standard treatment in ganglion cyst of the knee. However, a subcutaneous extension may lead to incomplete arthroscopic resection: Leaving behind the residual tissue which may cause recurrence. Therefore, proper pre-operative evaluation of MR images of these cases is very important.

A rare presentation in a case of parathyroid carcinoma.

Parathyroid carcinoma is a very rare endocrine malignancy, which usually presents with features of hypercalcaemia and a neck mass. Here a case of parathyroid carcinoma, whose only presenting feature was multiple pathological fractures, without any palpable neck mass is reported. En masse resection of the parathyroid mass along with ipsilateral hemithyroidectomy was performed, while the fractures were treated conservatively. At three years follow-up the patient does not have any recurrence or any evidence of metastasis.