Types Of Cancer Research Articles

Synthesis, computational analysis, and anti-proliferative evaluation of novel bithienylbenzamidine derivatives: Towards cytostatic cancer therapeutics

Our research unveils the synthesis and characterization of four novel monocationic 2,5-diarylbithiophene derivatives 4a-d, prepared through Suzuki cross-coupling reactions and subsequent amidine formation. Density Functional Theory (DFT) calculations provide unprecedented insights into the electronic properties and structure-activity relationships of these compounds. In vitro screening against the NCI-60 cancer cell panel demonstrates remarkable anti-proliferative activities. Compound 4c emerges as a standout candidate, exhibiting potent growth inhibition across multiple cancer types, with GI50 values as low as 0.36 µM against certain ovarian cancer lines. Intriguingly, our research suggests a potential shift from purely cytotoxic towards more cytostatic behavior, potentially offering improved therapeutic windows and reduced side effects. Molecular docking studies provide evidence for the compounds' interaction with human carbonic anhydrase IX, hinting at a possible mechanism of action. This comprehensive study not only introduces a promising new class of anti-cancer compounds but also provides a rich foundation of structural, electronic, and biological data to fuel future research. The bithienylbenzamidine derivatives, particularly compound 4c, represent exciting candidates for further development in the ongoing battle against cancer.

Generalizable and automated classification of TNM stage from pathology reports with external validation

Cancer staging is an essential clinical attribute informing patient prognosis and clinical trial eligibility. However, it is not routinely recorded in structured electronic health records. Here, we present BB-TEN: Big Bird – TNM staging Extracted from Notes, a generalizable method for the automated classification of TNM stage directly from pathology report text. We train a BERT-based model using publicly available pathology reports across approximately 7000 patients and 23 cancer types. We explore the use of different model types, with differing input sizes, parameters, and model architectures. Our final model goes beyond term-extraction, inferring TNM stage from context when it is not included in the report text explicitly. As external validation, we test our model on almost 8000 pathology reports from Columbia University Medical Center, finding that our trained model achieved an AU-ROC of 0.815–0.942. This suggests that our model can be applied broadly to other institutions without additional institution-specific fine-tuning.

Radixin: Roles in the Nervous System and Beyond.

Radixin is an ERM family protein that includes radixin, moesin, and ezrin. The importance of ERM family proteins has been attracting more attention, and studies on the roles of ERM in biological function and the pathogenesis of some diseases are accumulating. In particular, we have found that radixin is the most dramatically changed ERM protein in elevated glucose-treated Schwann cells. We systemically review the literature on ERM, radixin in focus, and update the roles of radixin in regulating cell morphology, interaction, and cell signaling pathways. The potential of radixin as a therapeutic target in neurodegenerative diseases and cancer was also discussed. Radixin research has focused on its cell functions, activation, and pathogenic roles in some diseases. Radixin and other ERM proteins maintain cell shape, growth, and motility. In the nervous system, radixin has been shown to prevent neurodegeneration and axonal growth. The activation of radixin is through phosphorylation of its conserved threonine residues. Radixin functions in cell signaling pathways by binding to membrane proteins and relaying the cell signals into the cells. Deficiency of radixin has been involved in the pathogenic process of diseases in the central nervous system and diabetic peripheral nerve injury. Moreover, radixin also plays a role in cell growth and drug resistance in multiple cancers. The trials of therapeutic potential through radixin modulation have been accumulating. However, the exact mechanisms underlying the roles of radixin are far from clarification. Radixin plays various roles in cells and is involved in developing neurodegenerative diseases and many types of cancers. Therefore, radixin may be considered a potential target for developing therapeutic strategies for its related diseases. Further elucidation of the function and the cell signaling pathways that are linked to radixin may open the avenue to finding novel therapeutic strategies for diseases in the nervous system and other body systems.

Albendazole nanosuspension coated granules for the rapid localized release and treatment of colorectal cancer

Albendazole (ABZ), an anthelmintic drug, has been repurposed to treat various types of cancers. However, poor solubility of ABZ, resulting in low bioavailability, limits its application. Nanosuspension is a versatile method for enhancing the dissolution of hydrophobic molecules, but a successful drying has been the biggest challenge in the field. The objective of this research is to formulate and optimize ABZ nanosuspension (NS) coated granules for rapid delivery of ABZ for the treatment of colorectal cancer. ABZ NS was prepared by dual centrifugation method using Kollidon® VA64 and sodium lauryl sulphate (SLS) as stabilizers. The processing method was optimized to obtain a stable nanosuspension with particle size < 300 nm. The optimized ABZ NS was coated on microcrystalline cellulose (MCC) to form the nano-coated granules (NCG) and filled in EUDRACAP® for colon targeted delivery. The ABZ NS and NCG achieved ∼ 60 % and ∼55 % drug release, respectively, in presence of bile salt at colonic pH. Half-maximal inhibitory concentration (IC50) of ABZ NS was found to be 1.18 ± 0.081 µM and 3.59 ± 0.080 µM in two colorectal cancer cell lines: HCT 116 and HT-29, respectively. In addition, In vitro 3D tumor assay revealed that ABZ NS has superior tumor growth inhibition activity compared to the control and pure ABZ. The preparation of ABZ NCG in EUDRACAP® could be a promising approach to achieve colon targeted delivery and to repurpose ABZ for the treatment of colorectal cancer.

A Latent Class Analysis of Nutrition Impact Symptoms in Cancer Survivors

Those with a cancer diagnosis report experiencing a wide range of nutrition impact symptoms, the prevalence of which varies by study, group, and cancer type. We aimed to identify groups of cancer survivors with specific patterns of nutrition impact symptoms. Two hundred and twenty-nine individuals attending oncology day ward and outpatient clinics completed a series of questionnaires and physical measurements. A latent class analysis was performed to identify subgroups based on 13 nutrition impact symptoms taken from the Patient Generated Subjective Global Assessment short form. The identified classes were subsequently compared using analysis of variance and chi-square tests, by sociodemographic, clinical and nutritional variables, and by the Global Health Status (GHS) and five functioning scales determined using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Three latent subtypes were identified: (1) Fatigue (n = 58, 28%); (2) Low Symptom Burden (n = 146, 64%), and (3) High Symptom Burden (n = 25, 11%). Those in the High Symptom Burden group were more likely to be female, were currently receiving some form of treatment, were diagnosed ≥two years, and had consumed less food than usual in the last month compared to those in the Low Symptom Burden group. Those in the Fatigue group were less likely to have reported their food intake to be unchanged and more likely to be diagnosed ≥two years than those in the Low Symptom Burden group. The EORTC-QLQ-C30 functioning and GHS scores were all significantly different between the three nutrition impact symptoms classes (p &lt; 0.001). This is the first study to examine heterogeneity of nutrition impact symptoms in Irish cancer survivors. The findings of this work will inform and allow for more individualised nutrition care. By tailoring interventions to these specific groups, we can enhance the precision of care, improve prognostic accuracy, and significantly elevate the quality of life of survivors. This work underscores the critical importance of symptom management in the continuum of cancer care, ensuring that every survivor receives comprehensive support tailored to their unique journey.

The Multifaceted Role of miR-23a in Cancer and Disease Progression

Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that play a crucial role in post-transcriptional gene regulation by modulating mRNA stability and translation. These evolutionarily conserved molecules undergo processing by ribonucleases Drosha and Dicer, ultimately joining the RNA-induced silencing complex to silence gene expression. Among them, miR-23a, located on chromosome 19, is significant for its roles in cell growth, differentiation, and various diseases, including cancer. Depending on the cancer type, miR-23a can function as both an oncogene and a tumour suppressor. While its overexpression often correlates with aggressive tumours, miR-23a holds promise as a biomarker for early cancer detection and a therapeutic target. Its diverse functions in cancer include promoting tumour growth and hindering immune responses, highlighting its potential for personalized medicine. Beyond cancer, miR-23a is involved in blood sugar regulation, insulin resistance, muscle atrophy, and other diseases. It modulates pathways in type 2 diabetes mellitus, muscle atrophy, leukemia, epilepsy, and osteoarthritis. This paper aims to comprehensively analyze the roles of miR-23a in cancer and other diseases, focusing on its regulatory mechanisms, target genes, and pathways. It also evaluates the potential of miR-23a as a biomarker and therapeutic target. Despite its significance, research gaps remain, particularly in understanding the interactions of miR-23a with other miRNAs and the detailed mechanisms underlying its role in various diseases. More research into miR-23a clustering and how it works with other miRNAs could help us learn more about it and find better ways to use it to diagnose and treat diseases.

Post-traumatic reactions and quality of life after pelvic exenteration for gynecologic cancer: a retrospective cohort study.

We examined post-traumatic reactions and quality of life in women with recurrent gynecologic cancer who underwent a pelvic exenteration (PE), a potentially life-saving radical surgery associated with life-altering sequelae. Twenty-one women who had completed PE at least 6months prior completed the Impact of Event Scale-Revised, a measure of post-traumatic stress, the Post-Traumatic Growth Inventory, a measure of post-traumatic growth, the Center for Epidemiologic Studies-Depression Scale, and the European Organization for Research and Treatment of Cancer 30-item core Quality of Life Questionnaire. We examined the associations between these outcome variables, and quality of life scores were compared to normative values for the general and gynecologic cancer populations. Thirty percent of women reported clinically significant post-traumatic stress symptoms and 71% endorsed clinically significant depressive symptoms. More post-traumatic stress was associated with less post-traumatic growth, more depressive symptoms, and worse quality of life. In general, women's quality of life was worse than the general population but comparable to women with stage III-IV ovarian cancer and women with cervical cancer. Social functioning was markedly lower in our sample and women reported more pain, diarrhea, and financial difficulties post-PE compared to published norms for the general population and women with ovarian or cervical cancer. There were no differences in quality of life based on age, type of PE, type of urinary diversion, or cancer type. Findings support long-term continued symptom management and the ongoing rehabilitation of patients to optimize physical, psychological, and social well-being in PE survivorship.

Overcoming Irinotecan Resistance by Targeting Its Downstream Signaling Pathways in Colon Cancer

Among the most popular chemotherapeutic agents, irinotecan, regarded as a prodrug belonging to the camptothecin family that inhibits topoisomerase I, is widely used to treat metastatic colorectal cancer (CRC). Although immunotherapy is promising for several cancer types, only microsatellite-instable (~7%) and not microsatellite-stable CRCs are responsive to it. Therefore, it is important to investigate the mechanism of irinotecan function to identify cellular proteins and/or pathways that could be targeted for combination therapy. Here, we have determined the effect of irinotecan treatment on the expression/activation of tumor suppressor genes (including p15Ink4b, p21Cip1, p27Kip1, and p53) and oncogenes (including OPN, IL8, PD-L1, NF-κB, ISG15, Cyclin D1, and c-Myc) using qRT-PCR, Western blotting, immunofluorescence (IF), and RNA sequencing of tumor specimens. We employed stable knockdown, neutralizing antibodies (Abs), and inhibitors of OPN, p53, and NF-κB to establish downstream signaling and sensitivity/resistance to the cytotoxic activities of irinotecan. Suppression of secretory OPN and NF-κB sensitized colon cancer cells to irinotecan. p53 inhibition or knockdown was not sufficient to block or potentiate SN38-regulated signaling, suggesting p53-independent effects. Irinotecan treatment inhibited tumor growth in syngeneic mice. Analyses of allograft tumors from irinotecan-treated mice validated the cell culture results. RNA-seq data suggested that irinotecan-mediated activation of NF-κB signaling modulated immune and inflammatory genes in mice, which may compromise drug efficacy and promote resistance. In sum, these results suggest that, for CRCs, targeting OPN, NF-κB, PD-L1, and/or ISG15 signaling may provide a potential strategy to overcome resistance to irinotecan-based chemotherapy.

Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report

Abstract Introduction/Objective The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis. Methods/Case Report A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established. Results (if a Case Study enter NA) NA Conclusion Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.

Clinical Manifestations and Molecular Identification of Giardia duodenalis in Pediatric and Adolescent Cancer Patients in Southwestern Iran.

This study aimed to investigate the clinical and molecular characteristics of Giardia duodenalis (G. duodenalis) infection and identify potential risk factors in children and teenagers with malignancies in Shiraz, southwestern Iran. A total of 200 fresh fecal samples were collected from children and adolescents suffering from 32 different cancer types at Amir, Nemazee, and Saadi hospitals affiliated with Shiraz University of Medical Sciences between October 2021 and May 2022. Direct microscopy using saline and iodine wet mount was conducted, and all fecal samples were rechecked by SSU-PCR. Subsequently, a specific fragment of the tpi gene was amplified on all samples for prevalence, sequencing, and assemblage identification. Our study found a 4% (8/200) prevalence of G. duodenalis using microscopy and PCR. The molecular findings were consistent with the microscopic results. All eight positive samples with SSU-rRNA gene were also detected as positive with tpi gene and were correctly sequenced. Among the examined cancer patients, two assemblages were identified: A [sub-assemblage AI (2/8, 25%) and sub-assemblage AII (3/8, 37.5%)] and B [sub-assemblage BIV (3/8, 37.5%)]. Notably, patients were more vulnerable to G. duodenalis infection after receiving at least 8 treatment episodes (p < 0.05) and displaying gastrointestinal symptoms (p > 0.05). The demographic characteristics of cancer patients with G. duodenalis infection and the statistical conclusions were separately detailed. The small sample size and low prevalence rate in this study hindered precise epidemiological conclusions. Nonetheless, the results suggest that G. duodenalis infection among cancer patients in Shiraz city originates from humans, without any specific animal groups (C-H) involved.

Homologous Peptide Foldamer Promotes FUS Aggregation and Triggers Cancer Cell Death.

Fused in sarcoma (FUS), a multifunctional deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein, has been implicated in various cancer types, including sarcoma and leukemia. Despite its association with these diseases, there has been limited exploration of FUS as a cancer therapy target, primarily because its dynamic nature makes it difficult to target specifically. In this study, we explored a kind of β-sheet peptide foldamer, named β4-TAT, to influence FUS aggregation by targeting its RNA recognition motifs (RRM). This approach leverages the noncovalent interaction characteristics of peptide self-assembly processes. The β4 sequence, derived from the FUS RRM β-sheet, in combination with TAT, a peptide known for its nuclear targeting capability, enables β4-TAT to bind specifically to the analogous β4 sequence within FUS. Notably, β4-TAT effectively induces FUS aggregation within cells, leading to the death of cancer cells. Our work developed a novel peptide foldamer-based strategy for inducing protein aggregation, paving the way for innovative therapeutic approaches in targeting FUS-associated cancers.

Predictors of breast cancer HER2-receptor positivity by MRI intuitive imaging features

BackgroundToday, breast cancer is the most diagnosed cancer worldwide. There are many different clinical presentations, radiological characteristics, and histological types of breast cancer. HER2 is overexpressed in a significant number of breast cancer cases reaching 20% of all breast cancers, and its overexpression is seen directly proportionate with a poor outcome and prognosis.MethodsWe started this cross-sectional research from January 2022–December 2023 on 202 breast cancer patients who had 220 lesions. The molecular subtypes of the different lesions were determined in all the included cases. Magnetic resonance imaging (MRI) studies were conducted in all included cases. The MRI parameters included conventional MRI, diffusion-weighted analysis, and dynamic post-contrast T1-weighted imaging.ResultsThe prevalence of irregular margins (P < 0.001), linear and segmental distribution (P = 0.044), heterogeneous pattern (P < 0.001), and type 2 curve was statistically significantly higher in the HER2-positive lesions. Nipple infiltration incidence showed statistically significant elevation in the HER2-positive lesions (P = 0.017). The lesions’ ADC and perilesional ADC in the HER2-positive lesions were also statistically significantly elevated. The best cutoff point of ADC to detect lesions with positive HER2 expression was > 0.885 × 10–3 mm2/s, with 65.7% sensitivity and 60% specificity, with a statistically significant value (p = 0.005).ConclusionsMagnetic resonance imaging of breast imaging is a promising noninvasive method for identifying breast tumors with the HER2 molecular subtype. Combining various radiological features by MRI may provide a conclusion for recognizing positive HER2 lesions.

A Pan-Cancer Analysis of GAPDH as a Common Biomarker for Various Cancers

Background: The present study aimed to investigate the expression level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and explore its prognostic value across 24 different human cancers. This investigation was conducted using comprehensive bioinformatics and in vitro approaches that involved multiple layers of analysis. Methods: GAPDH expression and methylation levels were assessed via bioinformatics tools and validated using cell lines through RNA sequencing and targeted bisulfite sequencing analyses. The potential prognostic significance of GAPDH was evaluated through the use of a Kaplan–Meier plotter. Additionally, cBioPortal was employed to investigate genetic alterations associated with this gene. Pathway analysis was conducted using DAVID. Furthermore, a correlation analysis between GAPDH expression and CD8+ T immune cells was performed using TIMER and CDT. Lastly, a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and drugs. Results: The GAPDH was found commonly up-regulated in 24 types of human cancers and its up-regulation was significantly correlated with the poor relapse-free survival (RFS) and overall survival (OS) of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. This implies that GAPDH plays a significant role in the development of these cancers. The GAPDH up-regulation was also noticed to be associated with the different clinicopathological features of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD patients. Pathway analysis has shown GAPDH involvement in different diverse pathways. Furthermore, notable correlations were observed between the expression of GAPDH and its promoter methylation level, genetic alterations, as well as the level of CD8+ T immune cells. Moreover, we identified significant regulatory drugs targeting GAPDH that have the potential to modulate its expression and potentially prevent conditions such as BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. Conclusion: Based on our findings, GAPDH emerged as a promising diagnostic and prognostic biomarker for BLCA, CESC, HNSC, KIRP, LIHC, and LUAD.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor A (VEGF-A) expressions in Ethiopian female breast cancer and their association with histopathologic features.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGF) play important role in breast tumor growth, invasion, metastasis, patient survival and drug resistance. The aim of this study was to evaluate the protein expression status of EGFR and VEGF-A, as well as their association with hormone receptor status and histopathological characteristics in the invasive type of female breast cancer among Ethiopians. The primary breast tumor tissues were obtained from 85 Ethiopian invasive breast cancer cases that underwent modified radical mastectomy (MRM) from June 2014 to June 2015. Their FFPE blocks were analyzed for EGFR and VEGF protein expressions using immunohistochemical techniques. The expressions were also correlated with histopathologic features. Epidermal growth factor receptor over-expression was observed in 22% of the tumor samples. VEGF-A expression was negative in 13.41%, low in 63.41%, moderate in 20.73%, and high in 2.44%. EGFR expression, but not VEGF-A, showed a significant inverse correlation with both estrogen receptor (ER) (P = 0.01) and progesterone receptor (PR) statuses (P = 0.04). EGFR and VEGF expressions did not show significant association with tumor size, grade, lymph node status or age at diagnosis. Epidermal growth factor receptor expression was most likely associated with ER and PR negative tumors. Assessments of multiple molecular markers aid to understand the biological behavior of the disease in Ethiopian population. It might also help to predict which group of patients might get more benefit from the selected treatment strategies and which are not.

Navigating Secondary Breast Angiosarcoma: a case report

BACKGROUND AND PURPOSE: Secondary breast angiosarcoma is a rare and aggressive malignancy that poses significant diagnostic and therapeutic challenges. Arising either from metastasis or as a complication of previous radiation therapy, it presents distinct clinical characteristics and prognostic implications compared to primary breast angiosarcoma. Understanding the unique features of secondary breast angiosarcoma is essential for guiding clinical decision-making and optimizing patient outcomes in the management of this challenging malignancy. METHODS: Imaging modalities such as mammography, ultrasound, or MRI may be used to evaluate the extent of the tumor, assess lymph node involvement, and detect distant metastases. A tissue biopsy is essential for confirming the diagnosis of angiosarcoma. Histopathological examination of the biopsy specimen helps to differentiate angiosarcoma from another breast tumor and determine the tumor grade. RESULTS: As angiosarcoma is relatively rare, there is a lack of detailed information regarding its progression. However, when compared to more common types of breast cancer, angiosarcoma of the breast generally carries a worse outlook. This is largely attributed to its tendency to be diagnosed later and its higher likelihood of rapid spread to distant sites within the body. CONCLUSIONS: Breast secondary angiosarcoma is associated with poor prognosis, often due to its aggressive nature and limited treatment options. Close monitoring, aggressive treatment strategies, and supportive care are essential in managing this challenging malignancy.

A discussion of pediatric therapy-related acute myeloid leukemia with a rare t(8;16) translocation

Abstract Introduction/Objective Secondary acute myeloid leukemia is a type of blood cancer that arises after a previous myeloid neoplasm or after exposure to chemotherapy. Certain genetic mutations and chromosomal abnormalities can occur as a result of said cytotoxic drug-related effects. Here, we discuss a case of secondary acute myeloid leukemia with a rare translocation following hemophagocytic lymphohistiocytosis Etoposide treatment in a 13-year-old female. After less than a year into her initial treatment, the patient presented to the emergency department with severe bone pain. A full hematologic workup was performed, including bone marrow biopsy, flow cytometry analysis, and subsequent genetic studies. A diagnosis of therapy-related acute myeloid leukemia was made. Genetic studies revealed a rare t(8;16) translocation which presents with a unique morphology and prognosis that will be discussed here. Methods/Case Report A 13-year-old female presented to the emergency department for evaluation of fever, myalgia, and swelling in her clavicle. The patient’s history was notable for hemophagocytic lymphohistiocytosis with subsequent Etoposide chemotherapy treatment which she received less than a year prior to her visit. CBC was notable for low white blood cell count, low hemoglobin, increased neutrophilic bands, and decreased lymphocytes. Given her past medical history and worsening pain without a clear reason, hematology was consulted. Results (if a Case Study enter NA) A blast count of 61.8% was reported via flow cytometry with the cells seen in the dim CD45+, moderate to bright side-scatter region, co-expressing CD4, CD14 (dim, heterogeneous), CD15, CD16 (dim), CD64, HLA-DR, and MPO. The bone marrow biopsy was described as hypercellular with the predominant cell type as blasts at 66.4%. Numerous hemophagocytic blasts were noted as well. Acute leukemia next generation sequencing panel revealed a t(8;16)(p11;p13.3) KATA6A::CREBBP fusion without other abnormalities in the evaluated genes. This workup as a whole rendered the diagnosis of acute myeloid leukemia with KAT6A::CREBBP. Conclusion Diagnosing acute myeloid leukemia with KATA6A::CREBBP is important for prognostic factors. Knowing the patient’s history regarding her prior chemotherapy with Etoposide is also imperative for distinguishing a de novo presentation of this rare subtype, versus a therapy-related myeloid neoplasm. The patient was started on chemotherapy for her acute myeloid leukemia shortly thereafter the diagnosis.

Effects of Thyroid Hormones on Cellular Development in Human Ovarian Granulosa Tumor Cells (KGN).

Ovarian cancer is a common malignant tumor in the female reproductive system, and Granulosa cell tumor (GCT) of the ovary is a rare type of ovarian cancer, which significantly threatens women's reproductive health. It has been reported that dysregulation of thyroid hormones (THs) may be closely related to the progression and prognosis of ovarian cancer. Moreover, THs regulate phosphorylation of signal transducer and activator of transcription (STAT3) and Octamer-binding transcription factor 4 (OCT4) expression. It has been reported that STAT3 and OCT4 play important roles in cellular development and tumorigenesis. However, the mechanisms by which THs affect the development of GCT are still remained unclear. To evaluate the effect of THs on human ovarian granulosa tumor cells (KGN), cells were treated with 3,5,3' -triiodothyronine (T3). Oct4 small interfering (Oct4 siRNA) or STAT3 inhibitor C188-9 was also co-cultured with cells in some experiments, respectively. The cell viability, proliferation, and proteins content were detected by CCK-8, EdU, and Western Blotting, respectively. The results showed that T3 enhanced cell viability and proliferation. Moreover, T3 also increased the expression of thyroid hormone receptor (TR), p-STAT3, and OCT4 proteins. The effects of T3 on both p-STAT3 and OCT4 expression were blocked by TR antagonist 1-850. Meanwhile, C188-9, an inhibitor of STAT3, decreased T3-induced cellular viability, proliferation, and OCT4 expression, highlighting that p-STAT3 can regulate the expression of OCT4 and affect cellular viability, and proliferation. Furthermore, T3-induced cellular growth was reduced by Oct4 siRNA, which indicates that T3 regulates cellular development through OCT4. These findings suggest that T3 increases cellular development via OCT4, which is mediated by phosphorylation of STAT3, and TR is also involved in these processes.

The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study.

The aim of this study was to determine the association between insulin glargine usage and the potential increase in cancer risk among the Lithuanian population diagnosed with type 2 diabetes mellitus (T2DM). A retrospective cohort study was conducted. The cohort of insulin users was established by identifying all male and female patients diagnosed with T2DM, as recorded in the National Health Insurance Fund database between 1 January 2000 and 31 December 2012. The risk of cancer among insulin glargine users was compared with the risk in non-glargine insulin users. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). The overall cancer risk for all sites combined showed no significant difference (HR 0.84, 95% CI 0.67-1.05). Although a general decrease in the risk of cancers was observed at most sites for glargine users, the use of insulin glargine was associated with a non-significant increase in the risk of mouth and pharynx, stomach, non-melanoma skin, breast, cervical, ovarian, and central nervous system cancers. There was a tendency for a lower risk of colon, rectum, rectosigmoid, and anus cancer among glargine users (HR 0.45, 95% CI 0.18-1.12, p = 0.09). Our research contributes to the growing body of evidence showing that insulin glargine is not associated with an increased risk of all cancers or specific types of cancer.

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

Tissue-resident T cells in Clinical Response and Immune-related Adverse Events of Immune Checkpoint Blockade.

T cell surveillance of tissues is spatially organized: circulating memory T cells perform surveillance of secondary lymphoid organs while tissue-resident memory T cells act as sentinels in barrier tissues. In the context of infection, tissue-resident memory T cells survive long term in barrier tissues and are poised to respond to re-encounter of infectious agents. The activity of such tissue-resident T cells is regulated by the PD-1 and CTLA-4 inhibitory receptors targeted by cancer immunotherapies. This review investigates the hypothesis that T cells with a tissue residency program play an important role in both protective anti-tumor immunity and immune-related adverse events (irAEs) of immune checkpoint blockade (ICB). A series of translational studies have demonstrated that a higher density of tissue-resident T cells within tumors is associated with favorable survival outcomes in a diverse range of cancer types. Tissue-resident T cells have also been implicated in clinical response to immune checkpoint blockade, and dynamic tracking of T cell populations in pre- and on-treatment tumor samples demonstrated that T cells with a tissue residency program responded early to ICB. Investigation of colitis and dermatitis as examples of irAEs demonstrated that tissue-resident memory T cells were reactivated at these epithelial sites, resulting in a highly cytotoxic state and secretion of inflammatory cytokines IFNγ and TNFα. It will therefore be important to consider how a tissue residency program can be enhanced to promote T cell-mediated tumor immunity while preventing the development of irAEs.