AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer.

Therapy resistance and metastatic progression are primary causes of cancer-related mortality. Disseminated tumor cells possess adaptive traits that enable them to reprogram their metabolism, maintain stemness, and resist cell death, facilitating their persistence to drive recurrence. The survival of disseminated tumor cells also depends on their ability to modulate replication stress in response to therapy while colonizing inhospitable microenvironments. In this study, we discovered that the nuclear translocation of AXL, a TAM receptor tyrosine kinase, and its interaction with WRNIP1, a DNA replication stress response factor, promotes the survival of HER2+ breast cancer cells that are resistant to HER2-targeted therapy and metastasize to the brain. In preclinical models, knocking down or pharmacologically inhibiting AXL or WRNIP1 attenuated protection of stalled replication forks. Furthermore, deficiency or inhibition of AXL and WRNIP1 also prolonged metastatic latency and delayed relapse. Together, these findings suggest that targeting the replication stress response, which is a shared adaptive mechanism in therapy-resistant and metastasis-initiating cells, could reduce metachronous metastasis and enhance the response to standard-of-care therapies. SIGNIFICANCE: Nuclear AXL and WRNIP1 interact and mediate replication stress response, promote therapy resistance, and support metastatic progression, indicating that targeting the AXL/WRNIP1 axis is a potentially viable therapeutic strategy for breast cancer.

Photodegradation of rhodamine-B in aqueous environment using visible-active gC3N4@CS-MoS2 nanocomposite.

Rapid industrial expansion leads to environmental pollution especially in an aqueous environment. Photocatalytic degradation is one of the most efficient and environmentally friendly techniques used to treat industrial pollution due to its complete degradation capability of a variety of water contaminants to their non-toxic state. Graphitic carbon nitride (gC3N4) and molybdenum disulfide (MoS2) provide efficient dye degradation, but MoS2 has few disadvantages. Hence, chitosan (CS) supported gC3N4-MoS2 hybrid nanocomposite was developed in this study to reduce these issues by accelerating the degradation of dye molecules such as rhodamine-B under visible light. The prepared gC3N4@CS-MoS2 hybrid nanocomposite was thoroughly characterized using various analytical tools including FTIR, XRD, SEM, EDX, XPS, UV-Visible, and PL spectra. Several influencing parameters such as irradiation time, initial pH, dosage, and initial dye concentration were optimized by batch mode. The photodegradation of rhodamine-B could be induced by the heterogeneous gC3N4@CS-MoS2-water hybrid nanocomposite. The narrow band gap of gC3N4@CS-MoS2 (1.80 eV) makes it suitable for effective degradation of rhodamine-B due to more active in the visible region and attained its highest degradation efficiency of 99% after 40 min at pH 8 with minimum dosage of 60 mg. The possible degradation mechanism was tentatively proposed for rhodamine-B dye molecules from aqueous environment. The present work shows a novel photocatalyst for the purification and detoxification of dye molecules as well as other water contaminants found in polluted wastewater.

Clinical Profiling of a Bilingual Client with Anomic Aphasia.

BACKGROUND: Aphasia is an acquired condition affecting auditory comprehension, verbal expression, reading, writing and word-finding abilities along with sensory-motor impairments. Anomia refers to difficulty in word retrieval or naming which is seen irrespective of the type of aphasia. However, if a patient shows word-finding difficulty, in specific, a diagnosis of Anomic aphasia is made. There are variations within anomic aphasia on which the management and recovery depend. The article provides one such case report. PURPOSE: Speech and language profiling in anomic aphasia, specific treatment strategies, the effect of bilingualism on recovery. METHODS: Mr S, a 38-year-old bilingual male reported 5 months post-stroke with difficulty in expressing, difficulty in writing and weakness in the right side of the body. Medical history was checked and speech and language evaluations including both formal and informal assessments were performed. After this, a diagnosis of Anomic aphasia with mild dysarthria was made. An appropriate speech-language therapeutic plan and specific activities were formulated for Mr S in his first language (L1) and he was given a therapy for a span of 3 months. A follow-up evaluation in both first and second language of the patient yielded differential recovery patterns. RESULTS: The diagnosis was affected by different variants of anomic aphasia; treatment was specific to the clinical profiling and followed life-participation approach of aphasia. The recovery was affected by differential recovery patterns between the languages. DISCUSSION: Factors pertaining to diagnosis, recovery, bilingualism and treatment of the client with anomic aphasia are discussed.