Nectin-4-directed antibody-drug conjugates (ADCs): Spotlight on preclinical and clinical evidence.

Nectin-4 (Nectin cell adhesion molecule 4), a type I transmembrane cell adhesion protein, was demonstrated to be overexpressed in a variety of tumors, making it an attractive antigen for targeted therapies such as antibody-drug conjugates (ADCs). Of great note, the US Food and Drug Administration (FDA)-approval of the first Nectin-4-directed ADC, enfortumab vedotin (EV), in urothelial cancer (UC) not only introduced Nectin-4 as a clinically validated and reliable target antigen but also confirmed the evolving role of Nectin-4-directed ADCs as novel and promising cancer therapeutics. In addition to EV, there have been or are currently being seven and eleven Nectin-4-directed ADCs, respectively, in various stages of clinical trials and preclinical development, offering a promising future for the treatment of Nectin-4-positive cancer patients. This study reviewed clinical- and preclinical-stage Nectin-4-directed ADCs.

Contrast-enhanced ultrasound (CEUS) as a follow-up method after the focal treatment of renal tumors: systematic review and meta-analysis.

CONTEXT: Contrast-enhanced ultrasound (CEUS) is a cost-effective radiation-free diagnostic method that can be used for renal tumor postoperative visualization after ablative treatment. OBJECTIVE: To assess CEUS diagnostic accuracy comparing with CT and MRI as a follow-up method in short-term and long-term postoperative periods after renal tumor ablation. MATERIALS AND METHODS: A systematic review and meta-analysis were performed in Scopus and Medline databases using the query "(kidney OR rena* OR RCC) AND (ablation OR RFA OR MWA OR cryo*) AND CEUS". The endpoint of the study was the evaluation of the overall accuracy of CEUS. RESULTS: Twelve trials were included in the review. With CT or MRI as a reference, for a short-term group (< 6 weeks after ablation) pooled sensitivity was 90.2%, I2 = 0%; pooled specificity was 99.3%, I2 = 0%; pooled NPV was 98.6%, I2 = 0%; pooled PPV was 94.6%, I2 = 0%; the AUC on the SROC curve was 0.971. For the long-term group (> 6 weeks after ablation), pooled sensitivity was 95.3%, I2 = 0%; pooled specificity was 97.6%, I2 = 0%; PPV was 74.2%, I2 = 4%; NPV was 99.4%, I2 = 5%; AUC = 0.93. CONCLUSION: CEUS has high sensitivity and specificity in ruling out the presence of local recurrence after renal tumor ablation with a higher risk of false-positive results within follow-up > 6 weeks compared with that for CT or MRI. Further studies with a unified protocol and morphological control of local renal tumor recurrence after ablation are needed.

The dynamic face of cadmium-induced Carcinogenesis: Mechanisms, emerging trends, and future directions.

Cadmium (Cd) is a malleable element with odorless, tasteless characteristics that occurs naturally in the earth's crust, underground water, and soil. The most common reasons for the anthropological release of Cd to the environment include industrial metal mining, smelting, battery manufacturing, fertilizer production, and cigarette smoking. Cadmium-containing products may enter the environment as soluble salts, vapor, or particle forms that accumulate in food, soil, water, and air. Several epidemiological studies have highlighted the association between Cd exposure and adverse health outcomes, especially renal toxicity, and the impact of Cd exposure on the development and progression of carcinogenesis. Also highlighted is the evidence for early-life and even maternal exposure to Cd leading to devastating health outcomes, especially the risk of cancer development in adulthood. Several mechanisms have been proposed to explain how Cd mediates carcinogenic transformation, including epigenetic alteration, DNA methylation, histone posttranslational modification, dysregulated non-coding RNA, DNA damage in the form of DNA mutation, strand breaks, and chromosomal abnormalities with double-strand break representing the most common DNA form of damage. Cd induces an indirect genotoxic effect by reducing p53's DNA binding activity, eventually impairing DNA repair, inducing downregulation in the expression of DNA repair genes, which might result in carcinogenic transformation, enhancing lipid peroxidation or evasion of antioxidant interference such as catalase, superoxide dismutase, and glutathione. Moreover, Cd mediates apoptosis evasion, autophagy activation, and survival mechanisms. In this review, we decipher the role of Cd mediating carcinogenic transformation in different models and highlight the interaction between various mechanisms. We also discuss diagnostic markers, therapeutic interventions, and future perspectives.

Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.

The cell-surface receptor tyrosine kinase c-mesenchymal-epithelial transition factor (c-Met) is overexpressed in a wide range of solid tumors, making it an appropriate target antigen for the development of anticancer therapeutics. Various antitumor c-Met-targeting therapies (including monoclonal antibodies [mAbs] and tyrosine kinases) have been developed for the treatment of c-Met-overexpressing tumors, most of which have so far failed to enter the clinic because of their efficacy and complications. Antibody-drug conjugates (ADCs), a new emerging class of cancer therapeutic agents that harness the target specificity of mAbs to deliver highly potent small molecules to the tumor with the minimal damage to normal cells, could be an attractive therapeutic approach to circumvent these limitations in patients with c-Met-overexpressing tumors. Of great note, there are currently nine c-Met-targeting ADCs being examined in different phases of clinical studies as well as eight preclinical studies for treating various solid tumors. The purpose of this study is to present a broad overview of clinical- and preclinical-stage c-Met-targeting ADCs.

Low-grade fibromyxoid sarcoma in laryngopharynx: the first case report in the literature.

Low-grade fibromyxoid sarcoma is a rare mesenchymal neoplasm with distinctive histopathological features. Although it typically arises in the deep soft tissues of the trunk and extremities, its occurrence in the head and neck region is exceedingly rare. We present the first documented case of low-grade fibromyxoid sarcoma in the laryngopharynx, expanding the spectrum of this rare tumor's anatomical localization. The clinical, radiological, and histopathological features of this unique case are discussed, highlighting the diagnostic challenges and therapeutic considerations associated with this uncommon presentation.

The Role of Innate and Adaptive Immune System in the Pathogenesis of Schizophrenia.

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia.

A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo.

In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.

In vitro pro-apoptotic and anti-metastatic potentials of harmaline-silver containing folate-linked chitosan nano-drug delivery system.

Objectives: Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells. Materials and Methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods. Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity. Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.

Impact of Melatonin as a Premedication Agent in Caesarean Section on Blood Loss and Postoperative Pain Level.

Background: Postpartum hemorrhage (PPH) is a serious postdelivery condition with a high incidence of morbidity and mortality for women who undergo childbirth with or without a caesarean section. Melatonin has been suggested to increase the contractility of myometrium and reduce the pain score postoperatively, therefore it is believed that the use of melatonin before surgery may decrease blood loss, reduce pain score, and decrease the need for postoperative opioids. Objectives: The main objectives of this study are focused on the investigation of melatonin as a premedication agent to reduce blood loss and decrease pain score postoperatively in patients undergoing cesarean section under spinal anesthesia. Methods: 80 patients were scheduled for spinal anesthesia-based cesarean sections and randomly assigned to two groups, melatonin group (M) 40 patients and placebo group (P) 40 patients to receive either 10 mg of sublingual melatonin or a placebo of 90 minutes preoperatively. Hemoglobin levels were been measured preoperative and 12 hrs. Postoperatively, blood loss volume was calculated by measuring both the weight of used materials before and after the surgery and the volume sucked in the suction bottle after placental delivery. Postoperative visual pain score and analgesic requirements were used to evaluate pain levels. Results: Analyzed collected data showed a significant decrease in blood loss in the melatonin group in comparison with the placebo group as measured by the hemoglobin level. On the other hand, there is a significant decrease in pain score and analgesia requirement with the melatonin group compared to the placebo group. Conclusion: Melatonin is a promising premedication drug that has a significant impact on postpartum hemorrhage by reducing blood loss and pain levels of mothers who have undergone C-sections.

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer.

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.

Photoactivation of pheophorbide-a utilizing 670 nm LEDs elicits cancer suppressive effects in androgen-independent prostate cancer cellular models.

OBJECTIVES: Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the USA. Photodynamic therapy (PDT) is a state-of-the-art treatment that combines high selectivity with minor side effects. Pheophorbide-a (Pheo) is a natural pigment with a photosensitizer property. Our study delved into the impact of Pheo alone or Pheo-PDT combination on the androgen-independent metastatic prostate cancer (AIPC) cell lines DU-145 and C4-2. Furthermore, an in-depth examination has been conducted on the photocytotoxicity mechanism of Pheo-PDT in these specific cell lines. METHODS: In vitro studies were conducted using the AIPC cell lines. DU-145 and C4-2 cells were treated with Pheo at different concentrations for 60 min alone, or Pheo treatment followed by exposure to 670 nm illumination (60 mW/cm2 in 88 s pulses), producing 5 J/cm2 via portable light-emitting diode. KEY FINDINGS: Our results show that Pheo-PDT substantially inhibits cell viability, anchorage-independent growth, and migration capacities and induces autophagy and apoptosis via the over-production of reactive oxygen species that mediates endoplasmic reticulum stress in AIPC cell lines. CONCLUSIONS: Our study highlights the potential benefits of Pheo-PDT in metastatic hormone-insensitive PCa cell lines. It paves the way for treating localized and locally advanced PCa as a possible candidate for castration-resistant prostate cancer.

Involvement of PI3K/HIF-1α/c-MYC/iNOS Pathway in the Anticancer Effect of Suaeda vermiculata in Rats.

Suaeda vermiculata Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment.

Basaloid squamous cell carcinoma of the larynx: A rare case report.

INTRODUCTION AND IMPORTANCE: Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive subtype of squamous cell carcinoma. BSCC in the larynx is an extremely rare occurrence, with only a few cases reported in the medical literature. This case report aims to shed light on the clinical presentation, diagnostic challenges, histopathological features, and therapeutic considerations associated with this rare entity. CASE PRESENTATION: This case report describes a 65-year-old male patient who presented with hoarseness and dyspnea. Laryngoscopy revealed a 2.5 cm pedunculated lesion on the left vocal cord. The patient underwent a laryngectomy, and the histopathological examination of the excised specimen confirmed the diagnosis of BSCC. CLINICAL DISCUSSION: BSCC of the larynx is a rare malignancy comprising less than 1 % of laryngeal cancers. Clinical features often overlap those of squamous cell carcinoma, such as hoarseness, progressive breathing difficulties, and swallowing issues. Treatment approaches vary, with some opting for neo-adjuvant radiotherapy before surgery, like in this case, while others favor surgical excision as the primary treatment, supplemented by adjuvant chemo- or radiotherapy in certain cases. CONCLUSION: Basaloid squamous cell carcinoma is a rare variant of squamous cell carcinoma. Clinicians and pathologists should be aware of the distinctive characteristics of BSCC and its potential clinical aggressiveness. While rare, early recognition and appropriate management are essential for achieving favorable outcomes in patients with this challenging condition.

Safety and efficacy of pimecrolimus versus vehicle for the treatment of atopic dermatitis in adults and paediatric population: a systematic review and meta-analysis.

Atopic dermatitis remains a widespread problem affecting various populations globally. While numerous treatment options have been employed, pimecrolimus remains a potent and viable option. Recently, there has been increasing interest in comparing the safety and efficacy of pimecrolimus with its vehicle. Methods: The authors conducted a comprehensive search of several databases, including PubMed, COCHRANE, MEDLINE, and Cochrane Central, from inception to May 2022, using a wide search strategy with Boolean operators. The authors also employed backward snowballing to identify any studies missed in the initial search. The authors included randomized controlled trials in our meta-analysis and extracted data from the identified studies. The authors used Review Manager (RevMan) Version 5.4 to analyze the data, selecting a random-effects model due to observed differences in study populations and settings. The authors considered a P-value of 0.05 or lower to be statistically significant. Results: The authors initially identified 211 studies, of which 13 randomized controlled trials involving 4180 participants were selected for analysis. Our pooled analysis revealed that pimecrolimus 1% was more effective at reducing the severity of atopic dermatitis than its vehicles. However, no significant difference was observed in adverse effects between pimecrolimus and vehicle, except for pyrexia, nasopharyngitis, and headache, which were increased with pimecrolimus. Conclusion: Our meta-analysis showed that pimecrolimus 1% is more effective than vehicle, although the safety profile remains inconclusive. Pimecrolimus reduced the Investigator's Global Assessment score, Eczema Area and Severity Index score, and severity of pruritus when compared to its vehicle, indicating a higher efficacy profile. This is one of the first meta-analyses to assess the efficacy and safety profile of pimecrolimus 1% against a vehicle and may assist physicians in making informed decisions.

Laser ablation of asphalt and coal in different solvents an In Vitro study.

Pulsed laser ablation in liquids (PLAL) is considered as green, cost effective, and facile method to produce nanocolloids which exhibit anticancer effect. When comparing breast cancer with other types of cancers, breast cancer is considered as the second cause of death in women. The objective of this article is to test the cytotoxicity of carbon-based materials prepared by PLAL on both the normal (REF) cell line and the human breast cancer (MCF7) cell line. In this study, PLAL is used to prepare nanocolloids of asphalt and coal in different solvents (ethanol, dimethyl sulfoxide (DMSO), phosphate buffer saline (PBS), and distilled water (DW)). A fiber laser of wavelength of 1.06 µm and an average power of 10 watts was used to prepare different nanocolloids in different solvents from asphalt and coal. The cytotoxic effect of the prepared materials was tested against breast cancer MCF7 cell line in vitro. The asphalt in both ethanol and DMSO was found to have a significant cytotoxic effect and the growth inhibition (GI) was found to be 62.1% and 50.5% at concentrations of 620 and 80 ppm respectively, unlike the coal in DMSO which showed G.I. of 59.5%. Both the prepared materials in the mentioned solvents showed low cytotoxicity against the normal cell line (REF). We can conclude that the organic materials prepared in organic solvents using the PLAL had shown a low cytotoxicity against the (REF) cell line while they exhibited a significant cytotoxic effect against the MCF7 cell line. Further studies are recommended to test these prepared materials in vivo.

Prevalence and risk factors of patients with chronic bronchitis among Iraqi adults.

This study aimed to identify the risk factors associated with chronic bronchitis among patients seeking medical attention for respiratory conditions in Al-Najaf Al-Ashraf city, Iraq. The study employed a case-control design and recruited 134 participants using convenient sampling. Data was collected using a questionnaire consisting of four parts which included demographic characteristics, individual factors, family history, and seasonal, environmental, and nutritional factors. The majority of participants were males aged between 21 and 35 years, with 71.8% of the study group residing in rural areas and 66.3% of the control group living in urban areas. We found that asthma was the most prevalent associated disease among chronic bronchitis patients, with 64.1% reporting it. The risk factors associated with chronic bronchitis were residency, smoking, exposure to secondhand smoke, respiratory sensitivity, dust sensitivity, spring sensitivity, hay fever, asthma, pulmonary obstruction, pneumonia, pertussis, and family history. The study highlights the need for smoking cessation, physical fitness, and healthy eating habits to prevent chronic bronchitis. The findings of this study are important for healthcare professionals in Iraq to design and implement effective prevention and management strategies for chronic bronchitis.

The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling.

The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-CoV-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin-converting enzyme 2 (ACE2). Here, we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway. Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and COVID-19 pathology. This may open new perspectives in the treatment of COVID-19 patients by targeting EGFR.

Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer.

Antibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity of a monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules to targeted cancer cells, leading to an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after the approval and tremendous success of trastuzumab emtansine and trastuzumab deruxtecan, representing a turning point in both HER2-positive breast cancer treatment and ADC technology. Additionally and importantly, a total of 29 ADC candidates are now being investigated in different stages of clinical development for the treatment of HER2-positive breast cancer. The purpose of this review is to provide an insight into the ADC field in cancer treatment and present a comprehensive overview of ADCs approved or under clinical investigation for the treatment of HER2-positive breast cancer.

Close, but no cigar: an unfortunate case of primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) is an uncommon and misunderstood disease, where little is known regarding its immunopathogenesis and appropriate treatment. Due to the constellation of nonspecific clinical features and imaging findings, PACNS is a diagnostic conundrum for clinicians and can be very difficult to treat. Case Presentation: A 64-year-old male with a history of prostate cancer presented to the emergency department with expressive aphasia and severe headache. Previously, he was diagnosed with ischemic strokes at outside hospitals and was subsequently initiated on anticoagulation medication but was later readmitted with a new onset of nontraumatic subarachnoid hemorrhage and later was found to have ischemic changes in the right temporoparietal lobe. He was suspected to have hypercoagulability of malignancy, as he was unresponsive to a wide variety of anticoagulants and his symptoms continued to deteriorate. On presentation, the physical examination was significant for right homonymous hemianopia, with positive antinuclear antibodies and notable erythrocyte sedimentation rate. The results from the full serologic workup was negative. Subsequent imaging of the brain revealed multifocal stenoses in multiple arteries. On further examination, digital subtraction angiography was concerning for vasculopathy, and was initiated on corticosteroids and cyclophosphamide. Discussion: This is one of the first cases of PACNS in which recurrent strokes were the presenting symptom for PACNS. Vasculitis should be a considered differential in patients with recurrent ischemic strokes and failed anticoagulant therapy. It is important to rule out malignancy and infectious causes due to the wide spectrum of conditions that cause central nervous system vasculitis.

c-MYC-Driven Polyamine Metabolism in Ovarian Cancer: From Pathogenesis to Early Detection and Therapy.

c-MYC and its paralogues MYCN and MYCL are among the most frequently amplified and/or overexpressed oncoproteins in ovarian cancer. c-MYC plays a key role in promoting ovarian cancer initiation and progression. The polyamine pathway is a bona fide target of c-MYC signaling, and polyamine metabolism is strongly intertwined with ovarian malignancy. Targeting of the polyamine pathway via small molecule inhibitors has garnered considerable attention as a therapeutic strategy for ovarian cancer. Herein, we discuss the involvement of c-MYC signaling and that of its paralogues in promoting ovarian cancer tumorigenesis. We highlight the potential of targeting c-MYC-driven polyamine metabolism for the treatment of ovarian cancers and the utility of polyamine signatures in biofluids for early detection applications.