Ape1 guides DNA repair pathway choice that is associated with drug tolerance in glioblastoma.

Ape1 is the major apurinic/apyrimidinic (AP) endonuclease activity in mammalian cells, and a key factor in base-excision repair of DNA. High expression or aberrant subcellular distribution of Ape1 has been detected in many cancer types, correlated with drug response, tumor prognosis, or patient survival. Here we present evidence that Ape1 facilitates BRCA1-mediated homologous recombination repair (HR), while counteracting error-prone non-homologous end joining of DNA double-strand breaks. Furthermore, Ape1, coordinated with checkpoint kinase Chk2, regulates drug response of glioblastoma cells. Suppression of Ape1/Chk2 signaling in glioblastoma cells facilitates alternative means of damage site recruitment of HR proteins as part of a genomic defense system. Through targeting "HR-addicted" temozolomide-resistant glioblastoma cells via a chemical inhibitor of Rad51, we demonstrated that targeting HR is a promising strategy for glioblastoma therapy. Our study uncovers a critical role for Ape1 in DNA repair pathway choice, and provides a mechanistic understanding of DNA repair-supported chemoresistance in glioblastoma cells.

Open tuber calcaneus fracture caused by a meat cleaver: A case report.

INTRODUCTION: Avulsion fractures of the tuber calcanei classically occur after falling on the foot, due to the forced dorsiflexion and the sudden contraction of the Achilles tendon. Direct trauma to the back of the leg and a direct penetrating injury are also infrequent causes and may be observed predominantly in younger patients. PRESENTATION OF CASE: We present a case of an open tuber calcaneus fracture resulting from a penetrating trauma in a 37-year-old patient. The fracture was reduced through the open wound and fixed using two cannulated screws. Bone union was radiologically and clinically observed at the end of the first year. DISCUSSION: During a physical altercation, the posterior of the patient's heel was struck directly with a meat cleaver. The position of the patient during the trauma can be considered to have increased the severity and depth of the injury. In addition, even though the injury radiologically resembled an avulsion fracture and was caused by direct trauma, the fact that it was open and that the mechanism of injury differed from the norm means that it should not be evaluated as a classic avulsion fracture in the full sense. Emergency open reduction and internal fixation were applied to an open calcaneal tuberosity fracture, and the patient was started on intravenous antibiotic therapy. CONCLUSION: Surgical techniques are successful in the treatment of open tuber calcanei fractures and an open intervention is usually required. Using cannulated screws is a good treatment option.

Arthroscopic treatment of synovial chondromatosis of the shoulder: A case report.

INTRODUCTION: Synovial chondromatosis is a mono-articular arthropathy rarely seen in diarthrodial joints. The classic treatment for synovial chondromatosis is open arthrotomy, synovectomy and complete removal of the free fragments. With recent advances in arthroscopic techniques and methods, the indications for arthroscopic treatment have been extended. PRESENTATION OF CASE: A 33-year old female presented with complaints of pain in the right shoulder. On the radiological examination, there were seen to be multiple calcified radio-opaque lesions filling all area of the glenohumeral joint. On computed tomography (CT) examination, again multiple radio-opaque free fragments were determined. Arthroscopy was applied to the right shoulder. The free fragments were completely removed. Approximately 33 free fragments, ranging in size from 0.5 to 1.3 cm, were removed. DISCUSSION: Cases of synovial chondromatosis in the shoulder have been rarely reported in literature. Generally the disease is self-limiting. Clinically, symptoms are generally not specific. Restrictions in the joint range of movement occur associated with the mechanical effect of the free fragments and in periods of active use, local pain and swelling may be seen in the shoulder. Simple removal of the free fragments, others have stated that removal with synovectomy is necessary to prevent recurrence of the cartilaginous metaplastic focus. Recurrence rates vary from 0 to 31%. CONCLUSION: Arthroscopic surgery can be successfully applied in the treatment of synovial chondromatosis. The advantages of the method include good visualisation during surgery, low morbidity and early healing.

Hydatid cyst of biceps brachii associated with peripheral neuropathy.

INTRODUCTION: Hydatidosis represents the most significant parasitic disorder in the Mediterranean countries and leads to major problems through unfavorable effects on the public health and national economy. Localization of the primary cyst hydatid infection in the extremity is rare and biceps brachii localization is also rarely reported in the literature. PRESENTATION OF CASE: A 43-year-old woman, who presented with the complaints of mass and pain in the left arm and numbness of the hand. Laboratory investigations, X-ray and magnetic resonance (MRI) findings revealed hydatid cyst of the biceps brachi muscle. The mass was totally excised and the diagnosis was confirmed by the macroscopic images of the mass and the pathologic results. After the surgery, the patient had an improvement in the nerve compression findings including numbness of the hand and the upper extremity and pain. DISCUSSION: Localization of a primary cyst hydatid infection in the upper extremity is rare and there are no reports of peripheral neuropathy secondary to mass effect. Even if the pre-surgical electromyelography performed for the nerve conduction study reveals a normal result, the potential for the hydatid cysts to cause nerve compression should be taken into consideration in such patients. CONCLUSION: Cases of concomitant neurologic findings and complaints secondary to peripheral nerve compression are very rare. The clinical findings should not be ruled out even if the EMG result is negative.

Upper extremity acute compartment syndrome during tissue plasminogen activator therapy for pulmonary embolism in a morbidly obese patient.

INTRODUCTION: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are more frequently observed in morbidly obese patients. Tissue plasminogen activator (tPA) is a thrombolytic agent which dissolves the thrombus more rapidly than conventional heparin therapy and reduces the mortality and morbidity rates associated with PE. Compartment syndrome is a well-known and documented complication of thrombolytic treatment. In awake, oriented and cooperative patients, the diagnosis of compartment syndrome is made based on clinical findings including swelling, tautness, irrational and continuous pain, altered sensation, and severe pain due to passive stretching. These clinical findings may not be able to be adequately assessed in unconscious patients. PRESENTATION OF CASE: In this case report, we present compartment syndrome observed, for which fasciotomy was performed on the upper right extremity of a 46-year old morbidly obese, conscious female patient who was receiving tPA due to a massive pulmonary embolism. DISCUSSION: Compartment syndrome had occurred due to the damage caused by the repeated unsuccessful catheterisation attempts to the brachial artery and the accompanying tPA treatment. Thus, the bleeding that occurred in the volar compartment of the forearm and the anterior compartment of the arm led to acute compartment syndrome (ACS). After relaxation was brought about in the volar compartment of the forearm and the anterior compartment of the arm, the circulation in the limb was restored. CONCLUSION: As soon as the diagnosis of compartment syndrome is made, an emergency fasciotomy should be performed. Close follow-up is required to avoid wound healing problems after the fasciotomy.

miR-125b targets ARID3B in breast cancer cells.

Mounting evidence suggests involvement of deregulated microRNA (miRNA) expression during the complex events of tumorigenesis. Among such deregulated miRNAs in cancer, miR-125b expression is reported to be consistently low in breast cancers. In this study, we screened a panel of breast cancer cell lines (BCCLs) for miR-125b expression and detected decreased expression in 14 of 19 BCCLs. Due to the heterogeneity of breast cancers, MCF7 cells were chosen as a model system for ERBB2 independent breast cancers to restore miR-125b expression (MCF7-125b) to investigate the phenotypical and related functional changes. Earlier, miR-125b was shown to regulate cell motility by targeting ERBB2 in ERBB2 overexpressing breast cancer cells. Here we showed decreased motility and migration in miR-125b expressing MCF7 cells, independent of ERBB2. MCF7-125b cells demonstrated profoundly decreased cytoplasmic protrusions detected by phalloidin staining of filamentous actin along with decreased motility and migration behaviors detected by in vitro wound closure and transwell migration assays compared to empty vector transfected cells (MCF7-EV). Among possible numerous targets of miR-125b, we showed ARID3B (AT-rich interactive domain 3B) to be a novel target with roles in cell motility in breast cancer cells. When ARID3B was transiently silenced, the decreased cell migration was also observed. In light of these findings, miR-125b continues to emerge as an interesting regulator of cancer related phenotypes.

Characterization of microRNA-125b expression in MCF7 breast cancer cells by ATR-FTIR spectroscopy.

MicroRNAs (miRNAs), are ~22 nucleotides long, non-coding RNAs that control gene expression post-transcriptionally by binding to their target mRNA's 3'UTRs (untranslated regions). Due to their roles in various important regulatory processes and pathways, miRNAs have been implicated in disease mechanisms such as tumorigenesis when their expression is deregulated. To date, a significant number of miRNAs and their target messenger RNAs (mRNAs) have been identified and verified. It is generally accepted that miRNAs can potentially bind to many mRNAs, which brings the requirement of validation of these interactions. While understanding that such individual interactions is crucial to delineate the role of a specific miRNA, we took a holistic approach and analyzed global changes in the cell due to expression of a miRNA in a model cell line system. Our model consisted of MCF7 cells stably transfected with miR-125b (MCF7-125b) and empty vector (MCF7-EV). MiR-125b is one of the known down-regulated miRNAs in breast cancers. In this study we examined the global structural changes in MCF7 cells lacking and expressing miR-125b by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy and investigated the dynamic changes by more sensitive spin-labelling Electron Spin Resonance (ESR) spectroscopy. Our results revealed less RNA, protein, lipid, and glycogen content in MCF7-125b compared to MCF7-EV cells. Membrane fluidity and proliferation rate were shown to be lower in MCF7-125b cells. Based on these changes, MCF7-125b and MCF7-EV cells were discriminated successfully by cluster analysis. Here, we provide a novel means to understand the global effects of miRNAs in cells. Potential applications of this approach are not only limited to research purposes. Such a strategy is also promising to pioneer the development of future diagnostic tools for deregulated miRNA expression in patient samples.