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Ugeskrift For Laeger May 2024
Topics: Humans; Condylomata Acuminata; Male; Female; Anus Neoplasms
PubMed: 38847314
DOI: 10.61409/V72029 -
Endoscopy Dec 2024
Topics: Humans; Anus Neoplasms; Male; Endoscopic Mucosal Resection; Carcinoma, Squamous Cell
PubMed: 38838728
DOI: 10.1055/a-2321-9527 -
Experimental and Molecular Pathology Jun 2024Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS...
BACKGROUND
Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions.
METHODS
Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach.
RESULTS
Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq.
CONCLUSION
mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.
Topics: Humans; Female; DNA Copy Number Variations; Paraffin Embedding; High-Throughput Nucleotide Sequencing; Formaldehyde; Tissue Fixation; Whole Genome Sequencing; Vulvar Neoplasms; Papillomavirus Infections; Anus Neoplasms
PubMed: 38820761
DOI: 10.1016/j.yexmp.2024.104906 -
Clinical Case Reports Jun 2024Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to...
Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to prevent the complications that may affect the development and growth of the child.
PubMed: 38803326
DOI: 10.1002/ccr3.8963 -
Viruses Apr 2024The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however,... (Review)
Review
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.
Topics: Humans; Papillomavirus Infections; Papillomavirus Vaccines; Female; Uterine Cervical Neoplasms; Papillomaviridae; Neoplasms; Vaccination; Anus Neoplasms; HIV Infections; Oropharyngeal Neoplasms; Male; Human Papillomavirus Viruses
PubMed: 38793561
DOI: 10.3390/v16050680 -
Journal of Inflammation Research 2024Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel...
BACKGROUND
Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa.
CASE REPORT
A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient's symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient's symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition.
CONCLUSION
Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.
PubMed: 38779428
DOI: 10.2147/JIR.S459548 -
Revue Medicale de Liege May 2024Although rare, around 2 % of digestive tumours, anal canal tumours remain a pathology that should not be neglected. These are frequently underdiagnosed due to the... (Review)
Review
Although rare, around 2 % of digestive tumours, anal canal tumours remain a pathology that should not be neglected. These are frequently underdiagnosed due to the affected region and the symptoms that can be confused with more common and benign pathologies such as haemorrhoids or anal fissures. The treatment of these tumours is mainly based on radio-chemotherapy to avoid heavy surgical treatment which remains the salvage option. This article aims to review the epidemiology, diagnosis, management, monitoring and future developments for these cancers.
Topics: Humans; Anus Neoplasms
PubMed: 38778649
DOI: No ID Found -
Aging May 2024This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic...
OBJECTIVE
This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways.
METHOD
Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation.
RESULTS
Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention.
CONCLUSIONS
PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.
Topics: Colorectal Neoplasms; STAT3 Transcription Factor; Humans; Animals; Mice; Protein Disulfide-Isomerases; Signal Transduction; Programmed Cell Death 1 Receptor; Cell Line, Tumor; Disease Progression; Tumor-Associated Macrophages; Cell Proliferation; Macrophages
PubMed: 38761176
DOI: 10.18632/aging.205847 -
MBio Jun 2024Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital...
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 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.
Topics: Female; Animals; Papillomavirus Infections; Microbiota; Vagina; Mice; Disease Models, Animal; Cervix Uteri; RNA, Ribosomal, 16S; Papillomaviridae; Viral Load
PubMed: 38742830
DOI: 10.1128/mbio.00933-24 -
European Journal of Medical Genetics Jun 2024Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly... (Review)
Review
Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.
Topics: Humans; Female; Micrognathism; Child, Preschool; Intellectual Disability; Transcription Factors; Neck; Hand Deformities, Congenital; Abnormalities, Multiple; DNA-Binding Proteins; Anorectal Malformations; Face; DNA Helicases; Nuclear Proteins; Anal Canal; Phenotype
PubMed: 38735569
DOI: 10.1016/j.ejmg.2024.104948