Emerging role of mucins in antibody drug conjugates for ovarian cancer therapy.

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages.

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads.

Deciphering cellular and molecular mechanism of MUC13 mucin involved in cancer cell plasticity and drug resistance.

There has been a surge of interest in recent years in understanding the intricate mechanisms underlying cancer progression and treatment resistance. One molecule that has recently emerged in these mechanisms is MUC13 mucin, a transmembrane glycoprotein. Researchers have begun to unravel the molecular complexity of MUC13 and its impact on cancer biology.

Synthesis and Antitumor Activity of Brominated-Ormeloxifene (Br-ORM) against Cervical Cancer.

Aberrant regulation of β-catenin signaling is strongly linked with cancer proliferation, invasion, migration, and metastasis, thus, small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that ormeloxifene (ORM), a triphenylethylene molecule that docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM.

The Hitchhiker's Guide to Spine Awake Surgery. The Oxford SAS Protocol and Early Outcomes.

Objective: Spine awake surgery (SAS) aims to achieve faster recovery times, better outcomes, and a lesser economic impact on society. Our drive to establish SAS was to improve patient outcomes and health economics during the COVID-19 pandemic. After a systematic review and to the best of our knowledge, SAS, the Oxford Protocol, is the first protocolized pathway that aims to train bespoke teams performing SAS safely, efficiently, and in a standardized repeatable fashion.

Anti-cancer activity of guggulsterone by modulating apoptotic markers: a systematic review and meta-analysis.

Guggulsterone (pregna-4,17-diene-3,16-dione; CHO) is an effective phytosterol isolated from the gum resin of the tree (Family Burseraceae) and is responsible for many of the properties of guggul. This plant is widely used as traditional medicine in Ayurveda and Unani system of medicine. It exhibits several pharmacological activities, such as anti-inflammatory, analgesic, antibacterial, anti-septic and anticancer.

Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore.

There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer.

Tannic Acid Exhibits Antiangiogenesis Activity in Nonsmall-Cell Lung Cancer Cells.

Nonsmall-cell lung cancer (NSCLC) is the most common type of lung cancer, with a dismal prognosis. NSCLC is a highly vascularized tumor, and chemotherapy is often hampered by the development of angiogenesis. Therefore, suppression of angiogenesis is considered a potential treatment approach.

Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells.

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients.

Multipoint fixation with vascularised fibular bone graft and myotomy for atlanto-axial instability in cervical dystonia: a case report.

Spinal instability is a challenging condition to manage in patients with cervical dystonia. Standard surgical stabilisation approaches may fail to cope with additional stress forces created by spasmodic muscles leading to construct failure either in the immediate or late post-operative period. Long-term stabilisation relies on the management of dystonic symptoms and adjunctive strategies to increase fusion success rate.

Frequency of hearing impairment in children between the ages of 2 and 10 years with middle ear infection.

This study was conducted on children between 2 and 10 years age to determine the frequency of hearing impairment in middle ear infection. It was a cross-sectional survey, done at Riphah International University from August 2018 to January 2019. Data was collected from the ENT Department of Children's Hospital Lahore through convenience sampling technique and included 52 patients with middle ear infection.

Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment.

Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications.

Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction.

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury.

Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer).

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models.

Next-generation paclitaxel-nanoparticle formulation for pancreatic cancer treatment.

Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic options. As pancreatic tumors are highly desmoplastic, they prevent appropriate uptake of therapeutic payloads. Thus, our objective is to develop a next-generation nanoparticle system for treating PanCa.

Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer.

Prostate cancer (PrCa) metastasis is the major cause of mortality and morbidity among men. Metastatic PrCa cells are typically adopted for aberrant glucose metabolism. Thus, chemophores that reprogram altered glucose metabolic machinery in cancer cells can be useful agent for the repression of PrCa metastasis.

A spinal infection with .

We present a case of a 60-year-old woman with an invasive spinal infection with associated with a 15-year-old spinal fixation device and epidemiological contact with dogs. It was confirmed on blood culture and culture from pus from the epidural abscess and successfully treated using similar treatment as for a infection 6 weeks of intravenous flucloxacillin 2 g four times daily with a 6 week follow-on course of oral clindamycin 450 mg three times daily. This case represents the first reported deep abscess forming infection with this recently discovered organism.

Ormeloxifene Suppresses Prostate Tumor Growth and Metastatic Phenotypes via Inhibition of Oncogenic β-catenin Signaling and EMT Progression.

Ormeloxifene is a clinically approved selective estrogen receptor modulator, which has also shown excellent anticancer activity, thus it can be an ideal repurposing pharmacophore. Herein, we report therapeutic effects of ormeloxifene on prostate cancer and elucidate a novel molecular mechanism of its anticancer activity. Ormeloxifene treatment inhibited epithelial-to-mesenchymal transition (EMT) process as evident by repression of N-cadherin, Slug, Snail, vimentin, MMPs (MMP2 and MMP3), β-catenin/TCF-4 transcriptional activity, and induced the expression of pGSK3β.

Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer.

In this study, we for the first time, investigated the potential anti-cancer effects of a novel analogue of cucurbitacin (Cucurbitacin D) against cervical cancer in vitro and in vivo. Cucurbitacin D inhibited viability and growth of cervical cancer cells (CaSki and SiHa) in a dose-dependent manner. IC50 of Cucurbitacin D was recorded at 400 nM and 250 nM in CaSki and SiHa cells, respectively.

Restitution of Tumor Suppressor MicroRNA-145 Using Magnetic Nanoformulation for Pancreatic Cancer Therapy.

Introduction: The functional significance of lost microRNAs has been reported in several human malignancies, including pancreatic cancer (PC). Our prior work has identified microRNA-145 (miR-145) as a tumor suppressor microRNA (miRNA) in pancreatic cancer. The restoration of miR-145 downregulates a number of oncogenes including mucin MUC13, a transmembrane glycoprotein that is aberrantly expressed in pancreatic cancer, thus efficiently inhibiting tumor growth in mice.

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression.

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression.

Curcumin Nanoformulation for Cervical Cancer Treatment.

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity.

Cyst or tumor in the buccomaxillary region: Review of literature and a case report.

Odontogenic tumors (OTs) include entities of a hamartomatous nature, such as odontoma, benign neoplasms like an adenomatoid odontogenic tumor (AOT), some benign neoplasms are aggressive as in the case of ameloblastoma. The AOT is a rare odontogenic tumor constituting only 3% of all the OT and very often misdiagnosed as an odontogenic cyst. We report a case of an intra-osseous type of AOT occurred in a young 16-year-old female located in the anterior maxilla along with the clinical, radiological, histological features, and literature review related to the tumor affecting the patient.