Neoplastic Disease Research Articles

Drug Repurposing: Exploring Potential Anti-Cancer Strategies by Targeting Cancer Signalling Pathways

The repurposing of previously clinically approved drugs as an alternative therapeutic approach to treating disease has gained significant attention in recent years. A multitude of studies have demonstrated various and successful therapeutic interventions with these drugs in a wide range of neoplastic diseases, including multiple myeloma, leukaemia, glioblastoma, and colon cancer. Drug repurposing has been widely encouraged due to the known efficacy, safety, and convenience of already established drugs, allowing the bypass of the long and difficult road of lead optimization and drug development. Repurposing drugs in cancer therapy is an exciting prospect due to the ability of these drugs to successfully target cancer-associated genes, often dysregulated in oncogenic signalling pathways, amongst which are the classical cancer signalling pathways; WNT (wingless-related integration type) and Hippo signalling. These pathways play a fundamental role in controlling organ size, tissue homeostasis, cell proliferation, and apoptosis, all hallmarks of cancer initiation and progression. Prolonged dysregulation of these pathways has been found to promote uncontrolled cellular growth and malignant transformation, contributing to carcinogenesis and ultimately leading to malignancy. However, the translation of cancer signalling pathways and potential targeted therapies in cancer treatment faces ongoing challenges due to the pleiotropic nature of cancer cells, contributing to resistance and an increased rate of incomplete remission in patients. This review provides analyses of a range of potential anti-cancer compounds in drug repurposing. It unravels the current understanding of the molecular rationale for repurposing these drugs and their potential for targeting key oncogenic signalling pathways.

Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis

Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment. CSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%; P < 0.0001). Concentrations of tumor DNA in CSF and plasma were positively correlated (Spearman’s ρ, 0.45; P = 0.03). For LMD diagnosis, cytology was 81.8% sensitive and CSF-tDNA was 91.7% sensitive. CSF-tDNA was also strongly prognostic for overall survival (HR = 7.1; P = 0.02). Among patients with progression on targeted therapy, resistance mutations, such as EGFR T790M and MET amplification, were common in peripheral blood but were rare in time-matched CSF, indicating differences in resistance mechanisms based on the anatomic compartment. In the osimertinib cohort, patients with CNS progression had increased CSF-tDNA VAFs at follow-up LP. Post-osimertinib CSF-tDNA VAF was strongly prognostic for CNS progression (HR = 6.2, P = 0.009). Detection of CSF-tDNA in lung cancer patients with suspected LMD is feasible and may have clinical utility. CSF-tDNA improves the sensitivity of LMD diagnosis, enables improved prognostication, and drives therapeutic strategies that account for spatial heterogeneity in resistance mechanisms.

Breast cancer in northern Peru: molecular subtypes and HER2 low.

This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients. Motivation for the study. Molecular classification of breast cancer allows the use of targeted treatments. Information on this profile in the northern macroregion of Peru is unknown. In addition, new therapies have appeared for a subgroup of patients. Main findings. In this study, the most frequent molecular subtypes were: luminal B, luminal A, triple negative and non-luminal HER2. Also, 18.3% of patients had low HER2 expression. Implications. Health policies should be aligned with scientific advances, to guarantee targeted therapies and to update the information in health manuals or protocols.

Unravelling epigenetic mechanisms in Cerastoderma edule genome: a comparison of healthy and neoplastic cockles

Cancer is a multifaceted genetic disease characterized by the acquisition of several essential hallmarks. Notably, certain cancers exhibit horizontal transmissibility, observed across mammalian species and diverse bivalves, the latter referred to as hemic neoplasia. Within this complex landscape, epigenetic mechanisms such as histone modifications and cytosine methylation emerge as fundamental contributors to the pathogenesis of these transmissible cancers. Our study delves into the epigenetic landscape of Cerastoderma edule, focusing on whole-genome methylation and hydroxymethylation profiles in heathy specimens and transmissible neoplasias by means of Nanopore long-read sequencing. Our results unveiled a global hypomethylation in the neoplastic specimens compared to their healthy counterparts, emphasizing the role of DNA methylation in these tumorigenic processes. Furthermore, we verified that intragenic CpG methylation positively correlated with gene expression, emphasizing its role in modulating transcription in healthy and neoplastic cockles, as also highlighted by some up-methylated oncogenic genes. Hydroxymethylation levels were significantly more elevated in the neoplastic samples, particularly within satellites and complex repeats, likely related to structural functions. Additionally, our analysis also revealed distinct methylation and activity patterns in retrotransposons, providing additional insights into bivalve neoplastic processes. Altogether, these findings contribute to understanding the epigenetic dynamics of bivalve neoplasias and shed light on the roles of DNA methylation and hydroxymethylation in tumorigenesis. Understanding these epigenetic alterations holds promise for advancing our broader understanding of cancer epigenetics.

Growth hormone therapy does not impact the development of intracranial hypertension in children with Chiari malformation.

Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT. The database of a pediatric endocrinology center was queried for patients with CM who received GHT from2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature ofsymptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated. GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS. Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

CD44 and its implication in neoplastic diseases.

CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of CD44 gene, CD44 is divided into two isoforms, the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v). Different isoforms of CD44 participate in regulating various signaling pathways, modulating cancer proliferation, invasion, metastasis, and drug resistance, with its aberrant expression and dysregulation contributing to tumor initiation and progression. However, CD44s and CD44v play overlapping or contradictory roles in tumor initiation and progression, which is not fully understood. Herein, we discuss the present understanding of the functional and structural roles of CD44 in the pathogenic mechanism of multiple cancers. The regulation functions of CD44 in cancers-associated signaling pathways is summarized. Moreover, we provide an overview of the anticancer therapeutic strategies that targeting CD44 and preclinical and clinical trials evaluating the pharmacokinetics, efficacy, and drug-related toxicity about CD44-targeted therapies. This review provides up-to-date information about the roles of CD44 in neoplastic diseases, which may open new perspectives in the field of cancer treatment through targeting CD44.

#2774 Association of serum CA-125 and lung ultrasound with other markers of volumen status in peritoneal dialysis patients

Abstract Background and Aims Volume overload (VO) represents the main risk factor for cardiovascular death in peritoneal dialysis (PD) patients. The lack of objective methods and validated markers constitutes the basis for the high prevalence, which is one of the main causes of technique failure. The use of lung ultrasound, VExUS score and serum CA-125 (SeCA-135), has emerged to assess volume in heart failure patients. In this pilot study, we explored the association of these novel approaches with classical markers of VO Method A cross-sectional cohort study was conducted on fourteen PD outpatients, in which volume status was simultaneously assessed through SeCA-125 levels along with standardized 28-site lung ultrasound, VExUS Score (excluding renal Doppler), NT-proBNP levels, and bioimpedance spectroscopy (BIS). Clinical and physical examination parameters were collected simultaneously, and echocardiographic measures were collected from the clinical history in the previous 6 months. The inclusion criteria were: patients over 18 years old, in a PD program for at least 6 months, with good adherence to the technique. The exclusion criteria were: cardiovascular event in the three months prior to the study initiation, active uncontrolled neoplastic disease, or active infection or intercurrent illness in the 2 months prior to evaluation. Because NT-ProBNP does not follow the normal distribution, we used the Ig transformation (LgNT-proBNP) in the statistical process. Results The mean age was 68.9 ± 14.9 years, with an average of 29.9 ± 19.61 months on dialysis, a mean residual diuresis of 1.22 ± 0.88 liters, and the mean weekly KT/V was 2.10 ± 0.63. 28.6% of the patients have Congestive Heart Failure, 57.1% have Diabetes Mellitus and 100% have hypertension. The patients had a mean Charlson Index of 5.7 ± 2.1 and were using an average of 2.4 ± 1.1 antihypertensive drugs. 28.6% of the patients presented dyspnea, 14.3% had pulmonary crackles, and 35.7% had peripheral edema. Mean ECW/TBW was 0.48 ± 0.02, and overhydration by BIS was 1.18 ± 1.46 L. The mean number of B-lines was 8.79 ± 6.43, Se-CA-125 was 20.42 ± 8.66 IU/mL, and NT-proBNP was 3950 (172-35,000) ng/L. SeCA125 was positively associated with left atrial volume (r = 0.823, p = 0.01), estimated PASP (r = 0.787, p = 0.03), LogNT-proBNP (r = 0.614, p = 0.02) and negatively correlated with TAPSE (r = −0.77, p = 0.05). Likewise, LogNT-proBNP was positively associated with CRP (r = 0.54, p = 0.05), and ECW/TBW ratio (r = 0.57, p = 0.03) and negatively correlated with albumin (r = −0.66, p = 0.01). There was no correlation between the number of B-lines and Se-CA-125 with the diameter or collapsibility of the IVC, pulsatility portal vein, or analysis of Doppler hepatic vein, VExUs grade, ECW/TBW ratio, NT-proBNP levels, renal residual function or the presence of edema or pulmonary crackles. Patients with overhydration by BIS (&amp;gt;7.5% OH/TBW) showed more B-lines (13 ± 6.32 vs. 5.57 ± 5.028 p = 0.04). Patients diagnosed as overloaded by B-lines (&amp;gt;5 lines) did not show a higher level of SeCA-125 (22.2 ± 9.50 vs 16 ± 4.16; p &amp;gt; 0.05), VCI diameter (1.6 ± 9.43 vs 2 ± 0.27; p &amp;gt; 0.05), OH/TBW ratio (8.4 ± 8.55 vs 2.55 ± 4.13; p &amp;gt; 0.05) or Log NT-proBNP (0.91 ± 0.76 vs 3.19 ± 0.91; p &amp;gt; 0.05). Conclusion The number of B-lines in lung ultrasound can detect patients with VO earlier compared to BIS. SeCA-125 levels are sensitive to changes in the echocardiogram. The use of both methods can help us detect early signs of volume overload in peritoneal dialysis patients.

#1231 Atypical uremic hemolytic syndrome diagnosis, therapeutic management, control and follow-up in pregnancy: about a case

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a clinical entity characterized by non immune hemolytic anemia, thrombopenia, and renal failure in which the lesions are mediated by a process of thrombotic microangiopathy, mutations in its genes that lead to uncontrolled activation. of C5 and formation of the membrane attack complex. Its correct diagnosis allows prescribing treatment based on eculizumab, a C5 inhibitor. The clinical case of a patient with aHUS is presented, who three months after diagnosis, becomes pregnant. The objective is to highlight the importance of early differential diagnosis for the early establishment of effective treatment of this pathology, as well as management during pregnancy, childbirth and the postpartum period. The pathophysiology, diagnosis and genetic study are updated, as well as the therapeutic management of aHUS. Case Reports 27 year old women with no personal or family history of interest. She went to the emergency room in the full pandemic by SARSCov2 due to choluric urine along with fever of 38, myalgias and generalized arthralgias. At that time, PCR positive SARSCov2, deterioration of renal function was noted with Creatinine of 1.8 mg/dl (previous normal), LDH 1954 u/l, Platelets 21000, Hemoglobin 14.4 g/dl without schistocytes in smear, albumin/creatinine ratios 8700 and intense hematuria. It was interpreted as thrombotic thrombocytopenic purpura receiving corticosteroids, rituximab and plasmapheresis. After 48 hours, thrombopenia persists, schistocytes appear in smears and renal function deteriorates creatinine to 2.8 mg/dl. ADAMS 13 is received at normal values, considering at this time a diagnosis of aHUS, the previous treatment is interrupted and a dose of eculizumab 900 mg is received, doses of 900 per week are scheduled for 4 weeks in the fifth week 1200 mg and from Then on biweekly dose 1200 mg of eculizumab. At the third week of treatment, renal function has already normalized, hemolysis data have disappeared, Htcro and platelets have returned to normal. Proteinuria and hematuria disappears which has been maintained up to now. Good tolerance to treatment without any incidence, presenting a positive pregnancy test at three months. During pregnancy treatment with eculizumab is maintained. We continued with the biweekly regimen with 1200 mg of eculizumab until delivery. Labor is induced at week 37 receiving a extra dose of 1200 mg in the first 24 hours of delivery and continuing with 4 doses of 1200 mg once a week. Afterwards the dose is changed to a biweekly dose without modifying it throughout lactation until it ends. The reason is to avoid complement deregulation in the context of pregnancy and therefore ensure blockade. Subsequently it is done Switch to ravulizumab when breastfeeding begins as follows: A loading dose of 2700 mg (according to the interval of patient's weight) 15 days after the last dose of eculizumab. The maintenance dose is 3300 mg every 8 weeks starting 2 weeks after the loading dose. Normal kidney function has been maintained. She presented on debut positive serology for parvovirus B19, receiving treatment with Immunoglobulins and PCR SARSCov2 was positive prescribing treatment with remdesivir. Vitus (CMV, HBV, HCV and HIV) serology was negative and autoimmune study as well as study of complement and proteinogram were negative or within normal limits. No data suggestive of a neoplastic process. Genetic study has been detected a pathogenic variant associated with aHUS. Conclusion We found a heterozygous carrier patient in genetic study, who developed aHUS during a Sars-cov2 infection, which could have been a trigger for its clinical expression. The clinical course of this case highlights how crucial it is to identify atypical hemolytic uremic syndrome. The early initiation of eculizumab improves the prognosis and quality of life, with pregnancy becoming increasingly more likely and therapy with eculizumab does not have safety problems in this regard, although pregnant patients with aHUS should be closely monitored close during pregnancy and postpartum.

Communicating the diagnosis of a hematological neoplastic disease to patients' minor children: a multicenter prospective study.

When a hematological malignancy is diagnosed, the whole family carries the burden of the disease; parents often try to protect minor children from suffering by avoiding communication about their disease. Since 2009, patients with minors at the Adult Hematology Division at San Gerardo Hospital (Monza) can take part in the "Emanuela Project": children can visit parents and talk with psychologists and hematologists, who explain the disease through simple metaphors. The EMY STUDY aimed to evaluate the impact of illness-related communication on children's behavior, comparing Monza's experience with other Hematology Units, where the communication is delegated to parents or psychological support. Questionnaires exploring the children's main behaviors (school performance, appetite, sleeping patterns, attachment to family figures, and family dialogue) were administered to both sick (SP) and healthy (HP) parents. From 2017 to 2021, 32 patients were enrolled, 20 from Monza and 12 from other hospitals; 84 questionnaires were globally collected. In Monza's group, no major changes in children's behavior were observed and an open dialogue about the disease was often possible. Disease communication is considered crucial and perceived as a responsibility of parents together with a professional figure, mainly the hematologist. Patients were satisfied with "Emanuela Project," reporting positive effects on doctor-patient relationship. Difficulties in separation were significantly higher at other hospitals (P=.019) than in Monza. While at other centers communication is considered parents' responsibility, Monza's patients emphasize the role of professional figures (P=.007). Differently from other hospitals, the role of the hematologist is crucial to Monza's patients (P = .001). Disease communication to patients' offspring is a crucial moment in the process of care, and the hematologist can play a major role in this difficult task, with potential positive effects both on children's well-being and on doctor-patient relationship.

Lymphomatoid papulosis. Case in pediatric dermatological clinical practice

A clinical case of lymphomatoid papulosis in a 10-year-old boy is described, clinically characterized by the presence of ulcerating nodes that resolve with the atrophy formation. The patient’s differential diagnostic workup included cutaneous anaplastic large cell lymphoma, cutaneous tuberculosis, polyarteritis nodosa, erythema nodosum, deep lupus erythematosus, and alpha-1 antitrypsin deficiency. Based on the history, clinical picture, as well as laboratory and instrumental studies, the patient was diagnosed with lymphomatoid papulosis. During the examination, no concomitant neoplastic diseases were identified in the patient. All elements resolved with the outcome being hyperpigmented spots and atrophy. To date, the relapse-free period of the disease in the patient is 10 months.

Abstract B009: Targeting bladder cancer-macrophage interactions by SPARC peptides

Abstract Bladder cancer is one of the privileged cancers treated with two modalities of immune therapeutics: intravesical Bacille Calmette-Guérin (BCG) for non-muscle invasive disease and immune checkpoint inhibitors for advanced metastatic muscle invasive disease. However, recurrence, intolerance and adverse events are encountered in both modalities with limited second and third line treatment options. Clinical data indicated that pretreatment infiltration of bladder tumors with tumor associated macrophages (TAMs) is associated with BCG failure, resistance to standard of care chemo- and immune-therapy and poor disease outcome. Preclinical studies indicated that macrophage infiltration is the forerunner of carcinogen-induced preneoplastic bladder lesions and progresses throughout overt neoplastic and metastatic disease. Thus, TAMs represent a plausible therapeutic target for bladder cancer. Capitalizing on our earlier report that SPARC, as tumor suppressor of BCa, we developed peptides mapping the biologically active domains of SPARC and investigated their direct effect on tumor cell malignant phenotype. In tandem, we determined the effect of SPARC-peptides on macrophage differentiation, polarization, and anti-tumor effects. We identified a potent inhibitory effect of our peptides on a panel of bladder cancer cell survival and invasiveness in 2D and 3D cultures. Using macrophage cell lines as well as bone marrow-derived myeloid cells, we found these peptides induced an M1 phenotype in response to cytokine stimulation, with enhanced phagocytic activity and macrophage-induced tumor cell killing in vitro. Moreover, SPARC-peptides inhibited macrophage polarization to M2 phenotype. Our data strongly suggest that SPARC-peptides are promising therapeutic candidates for bladder cancer. Citation Format: Mariam Diab, Neveen Said. Targeting bladder cancer-macrophage interactions by SPARC peptides [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B009.

Canine Euthanasia's Trend Analysis during Thirty Years (1990-2020) in Italy: A Veterinary Hospital as Case Study.

This study aimed to investigate changes in the number of, and reasons for, requests for dogs' euthanasia over the last thirty years. Data (breed, age, gender, neuter status, manner, and cause of death) from dogs' euthanasia registered between 1990 and 2020 in a small animals' veterinary hospital were analyzed. The overall period examined has been split into two terms (T1 = 1990-2004 and T2 = 2005-2020) considering the introduction and enforcement of Law 189/2004. During the whole period examined, a significant increasing trend in euthanasia cases has been recorded (p = 0.027). Comparing the two terms, we observed significant differences regarding variables such as age, breed, reproductive status, and ownership. The number of euthanized dogs was significantly higher in T1 than in T2. Dogs euthanized in T2 were older than dogs in T1. A high percentage of the euthanized dogs were crossbred and stray dogs. Additionally, the number of neutered/spayed dogs was significantly higher. Regarding the cause of death, a significantly higher percentage of neoplastic processes was detected in T2. The data here reported suggest a potential influence of Law 189/2004. This law in Italy has proven to be a legal milestone that has influenced the decision-making process between euthanasia and natural death.

P16 Expression in Multinucleated Stromal Cells of Fibroepithelial Polyps of the Anus (FEPA): A Comprehensive Review and Our Experience

Fibroepithelial polyps of the anus (FEPA) are a common benign polypoid proliferation of the stroma covered by squamous epithelium. They are also an often-overlooked part of pathological practice. Currently, immunohistochemistry (IHC) for p16 is the only recommended test for anal intraepithelial neoplasia, but the expression of p16 in stromal multinucleated atypical cells in FEPA has not been described. We aimed to evaluate the expression of p16 in stromal multinucleated atypical cells in FEPA and its role as a diagnostic biomarker to determine the origin of the atypical multinucleated cells in the stroma of FEPA and to rule out the possibility of a neoplastic process. Therefore, we researched a series of 15 FEPA in middle-aged patients histologically and by IHC. Examination of the subepithelial connective tissue from the FEPA showed bizarre, multinucleated cells, while their causal relationship with human papillomavirus (HPV) infection was rejected. In all cases, these cells showed mild to moderate atypical nuclear features and positive expression for p16, while the overlying squamous epithelium was negative. We concluded that FEPA are benign lesions in the stroma where mononuclear and multinucleated (sometimes atypical) cells showing fibroblastic and myofibroblastic differentiation can be found. Nevertheless, we believe that these cells have a practical diagnostic significance, although sometimes the presence of giant cells is difficult to establish, especially in the inflammatory context. The histological similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent the reactive hyperplasia of subepithelial fibrous connective tissue of the anal mucosa.

Ancient Diseases in Vertebrates: Tumours through the Ages

Paleo-oncology studies neoplastic diseases in fossilised animals, including human remains. Recent advancements have enabled more accurate diagnoses of ancient pathologies despite the inherent challenges in identifying tumours in fossils—such as the rarity of well-preserved specimens, the predominance of bone remains, and the difficulty in distinguishing neoplastic from non-neoplastic lesions. This study compiles reports of tumours in fossilised animals, highlighting that neoplasms are present in a wide range of vertebrates and drawing comparisons to modern instances of similar diseases. The findings underscore the multifactorial aetiology of tumours, which involves genetic, environmental, and lifestyle factors, and suggest that tumours have been around for at least 350 million years.

Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model.

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.

Circulating hypervirulent Marek's disease viruses in vaccinated chicken flocks in Taiwan by genetic analysis of meq oncogene.

Marek's disease (MD) is an important neoplastic disease caused by serotype 1 Marek's disease virus (MDV-1), which results in severe economic losses worldwide. Despite vaccination practices that have controlled the MD epidemic, current increasing MD-suspected cases indicate the persistent viral infections circulating among vaccinated chicken farms in many countries. However, the lack of available information about phylogeny and molecular characterization of circulating MDV-1 field strains in Taiwan reveals a potential risk in MD outbreaks. This study investigated the genetic characteristics of 18 MDV-1 strains obtained from 17 vaccinated chicken flocks in Taiwan between 2018 and 2020. Based on the sequences of the meq oncogene, the phylogenetic analysis demonstrated that the circulating Taiwanese MDV-1 field strains were predominantly in a single cluster that showed high similarity with strains from countries of the East Asian region. Because the strains were obtained from CVI988/Rispens vaccinated chicken flocks and the molecular characteristics of the Meq oncoprotein showed features like vvMDV and vv+MDV strains, the circulating Taiwanese MDV-1 field strains may have higher virulence compared with vvMDV pathotype. In conclusion, the data presented demonstrates the circulation of hypervirulent MDV-1 strains in Taiwan and highlights the importance of routine surveillance and precaution strategies in response to the emergence of enhanced virulent MDV-1.

The multidisciplinary approach in primary cutaneous lymphomas

Primary cutaneous lymphomas are a heterogeneous group of neoplastic diseases in which dermatological examination plays the pivotal role toward a management which must be multidisciplinary by definition [...].

Galectin-3 expression by thyroid neoplasms in a center in southwest Nigeria

Background: Galectin-3 (GAL-3), which is known to be expressed in certain normal tissues and is implicated in tumor progression and metastasis, serves as a valuable marker for distinguishing malignant thyroid lesions from benign thyroid lesions. This study aimed to assess the clinical and histopathological features of thyroid neoplasms at OAUTHC Ile Ife utilizing GAL-3 immunohistochemistry and to compare these findings with those of studies conducted in other regions of the world. Materials and Methods: Histology slides from 56 patients with thyroid neoplasms spanning a 20-year period were subjected to immunohistochemical staining with monoclonal antibodies against GAL-3. Evaluation was based on the 2022 World Health Organization Classification of Thyroid Neoplasms, categorizing marker expression as follows: 1+ (10–25% stained cells), 2+ (26–50% stained cells), 3+ (51–75% stained cells), and 4+ (&gt;75% stained cells). Negative staining indicated no staining, while localized staining (focal) represented &lt;50% of cells stained (1+ or 2+), and diffuse staining indicated &gt;50% of cells stained (3+ or 4+). Results: A total of 56 patients with neoplastic thyroid disease were studied, including 15 males and 41 females. Among the 16 benign neoplastic lesions, four (25.0%) exhibited focal GAL-3 expression, while 12 (75.0%) showed no expression. Among the forty malignant neoplastic lesions, five (12.5%) tested negative for the GAL-3 immunomarker, while 35 (87.5%) demonstrated positive expression to varying degrees. Among the positive malignant lesions, two (5.0%) displayed focal GAL-3 expression, while 33 (82.5%) exhibited diffuse staining of tumor cells. The diffuse and strong expression of GAL-3 was significantly greater in malignant thyroid neoplasms than in benign neoplasms (p&lt;0.05). The sensitivity and specificity of GAL-3 were 88% and 75%, respectively. Conclusion: Our findings align with the previous research indicating that diffuse and strong immunohistochemical expression of GAL-3 is indicative of thyroid gland malignancy. GAL-3 serves as a valuable tool in diagnosing thyroid neoplasms, particularly in cases where histomorphologic characteristics are inconclusive or unclear.

Gene expression profiling of &lt;i&gt;p53&lt;/i&gt; and &lt;i&gt;c-myc&lt;/i&gt; in HTLV-1 positive blood donors in Congo

Gene expression profiling of &lt;i&gt;p53&lt;/i&gt; and &lt;i&gt;c-myc&lt;/i&gt; in HTLV-1 positive blood donors in Congo

Unusual hypocalcemia in the context of neoplastic disease

Unusual hypocalcemia in the context of neoplastic disease