Editorial: Optimizing Schools of Cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Detection of non-haematolymphoid malignancies in bronchoalveolar lavages-A cancer centre's 10 year experience.

INTRODUCTION: Fibreoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) is often performed in immunocompromised and cancer patients to investigate possible infectious and non-infectious causes of clinical and radiological respiratory abnormalities. Knowledge of the incidence and distribution of non-haematolymphoid malignancies (NHLM) detected by FOB-BAL in this population is limited. METHOD: Our pathology electronic database was searched from July 1, 2008 to June 30, 2018 for BAL specimens with diagnoses of "malignant" and a review of the pathology report and electronic medical record was performed. Statistical analyses were performed to determine the incidence, distribution of NHLM, and demographics of patients in these BALs. RESULTS: A total of 209 (1.92%) out of 11 035 BAL cases were reported in the "malignant" category. After exclusion of 22 cases with haematolymphoid malignancies, 187 cases were included in this study. The average patient age was 58 years (ranging from 9 to 83 years). The most common NHLM identified were from lung/thoracic primaries (n = 103; 55.1%) with adenocarcinoma being the most common type of lung primary (n = 91; 88%). Other tumours detected included carcinomas from breast (n = 34; 18.2%), gastrointestinal tract (n = 17; 9.1%), genitourinary tract (n = 13; 7%), Müllerian origin (n = 8; 4.3%), and head and neck (n = 6; 3.2%). Rarer NHLM encompassed 3.2% of BALs (n = 6). CONCLUSION: FOB-BAL is a useful tool for evaluating various pulmonary abnormalities in our cancer institute's patient population and a valuable method for detecting NHLM, which is critical to guide appropriate subsequent therapies.

Indole Alkaloid Derivative B, a Novel Bifunctional Agent That Mitigates 5-Fluorouracil-Induced Cardiotoxicity.

Clinically approved therapeutics that mitigate chemotherapy-induced cardiotoxicity, a serious adverse effect of chemotherapy, are lacking. The aim of this study was to determine the putative protective capacity of a novel indole alkaloid derivative B (IADB) against 5-fluorouracil (5-FU)-induced cardiotoxicity. To assess the free-radical scavenging activities of IADB, the acetylcholine-induced relaxation assay in rat thoracic aorta was used. Further, IADB was tested in normal and cancer cell lines with assays gauging autophagy induction. We further examined whether IADB could attenuate cardiotoxicity in 5-FU-treated male ICR mice. We found that IADB could serve as a novel bifunctional agent (displaying both antioxidant and autophagy-modulating activities). Further, we demonstrated that IADB induced production of cytosolic autophagy-associated structures in both cancer and normal cell lines. We observed that IADB cytotoxicity was much lower in normal versus cancer cell lines, suggesting an enhanced potency toward cancer cells. The cardiotoxicity induced by 5-FU was significantly relieved in animals pretreated with IADB. Taken together, IADB treatment, in combination with chemotherapy, may lead to reduced cardiotoxicity, as well as the reduction of anticancer drug dosages that may further improve chemotherapeutic efficacy with decreased off-target effects. Our data suggest that the use of IADB may be therapeutically beneficial in minimizing cardiotoxicity associated with high-dose chemotherapy. On the basis of the redox status difference between normal and tumor cells, IADB selectively induces autophagic cell death, mediated by reactive oxygen species overproduction, in cancer cells. This novel mechanism could reveal novel therapeutic targets in chemotherapy-induced cardiotoxicity.

Anti-inflammatory, analgesic and antioxidant activities of novel kyotorphin-nitroxide hybrid molecules.

Mitochondrial oxidative damage contributes to a wide range of pathologies, including ischemia/reperfusion (I/R) injury, cardiovascular disorders and neurodegenerative diseases. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel kyotorphin-nitroxide hybrid molecules, and examined their free radical scavenging activities, in addition to their anti-inflammatory and analgesic activities. We have further characterized these compounds in a simulated I/R cellular model. Our findings suggest that the protective effects of kyotorphin-nitroxides partially reside in maintaining optimal mitochondrial function.

Lysosomal targeting with stable and sensitive fluorescent probes (Superior LysoProbes): applications for lysosome labeling and tracking during apoptosis.

Intracellular pH plays an important role in the response to cancer invasion. We have designed and synthesized a series of new fluorescent probes (Superior LysoProbes) with the capacity to label acidic organelles and monitor lysosomal pH. Unlike commercially available fluorescent dyes, Superior LysoProbes are lysosome-specific and are highly stable. The use of Superior LysoProbes facilitates the direct visualization of the lysosomal response to lobaplatin elicited in human chloangiocarcinoma (CCA) RBE cells, using confocal laser scanning microscopy. Additionally, we have characterized the role of lysosomes in autophagy, the correlation between lysosome function and microtubule strength, and the alteration of lysosomal morphology during apoptosis. Our findings indicate that Superior LysoProbes offer numerous advantages over previous reagents to examine the intracellular activities of lysosomes.

Quantification of Protoporphyrin IX Accumulation in Glioblastoma Cells: A New Technique.

Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After treatment with a series of 5-ALA doses, both PpIX and YFP fluorescence were measured. The ratio of PpIX to YFP fluorescence was calculated. Results. YFP fluorescence permitted the quantification of cell numbers and did not interfere with 5-ALA metabolism. The PpIX/YFP fluorescence ratio provided accurate relative PpIX levels, allowing for the assessment of PpIX accumulation in tissue. Conclusion. Constitutive YFP expression strongly correlates with cell number and permits PpIX quantification. Absolute PpIX fluorescence alone does not provide information regarding PpIX accumulation within the cells. Our research indicates that our PpIX/YFP ratio assay may be a promising model for in vitro 5-ALA testing and its interactions with other compounds during FGR surgery.