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Asian Pacific Journal of Cancer... Jun 2024Mucin-producing cholangiocarcinoma (MPCC) was rare biliary tract malignancy. Studies regarding this type of cholangiocarcinoma (CCA) were limited, particularly the... (Comparative Study)
Comparative Study
BACKGROUND
Mucin-producing cholangiocarcinoma (MPCC) was rare biliary tract malignancy. Studies regarding this type of cholangiocarcinoma (CCA) were limited, particularly the survival outcome. We aim to evaluate the survival rate, median survival time after surgery among CCA patients and to determine the association between MPCC and survival.
OBJECTIVE
To evaluate survival rate, median survival time after surgery among cholangiocarcinoma patients and to determine the association between mucin-producing cholangiocarcinoma and survival.
METHODS
CCA patients who underwent surgery between 2013 and 2020 from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand were included in the study. The MPCC was based on pathological findings after surgery. The survival of CCA patients was verified through medical records and civil registration. Survival rates and median survival time since the date of CCA surgery and its 95% confidence intervals (CI) were estimated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by adjusted hazard ratios (AHR) and their 95% CI.
RESULTS
Of 1,249 CCA patients which constituted 24,593 person-months, 687 died at the completion of the study. The overall incidence rate was 2.79 per 100 patients per month, the median survival time was 21.77 months (95% CI: 19.87 - 23.84), and the 5-year survival rate was 28.29% (95% CI: 24.99 - 31.67). From these patients, 210 (16.81%) were MPCC, the incidence rate was 1.81 per 100 patients per month, median survival time was 41.21 months (95% CI: 26.16 - 81.97), and 5-year survival rate was 44.69% (95% CI: 32.47 - 56.16). MPCC were 35% less likely to died compared with non-MPCC (AHR = 0.65; 95% CI: 0.50 - 0.84).
CONCLUSIONS
Our study revealed that CCA patients with MPCC had longer survival times and higher survival rates than those without MPCC. This classification will lead to appropriate treatment guidelines for CCA patients.
Topics: Humans; Cholangiocarcinoma; Female; Male; Bile Duct Neoplasms; Middle Aged; Survival Rate; Thailand; Prognosis; Aged; Mucins; Follow-Up Studies
PubMed: 38918677
DOI: 10.31557/APJCP.2024.25.6.2139 -
BioRxiv : the Preprint Server For... Jun 2024Injury can cause differentiated cells to undergo massive reprogramming to become proliferative to repair tissue via a cellular program called paligenosis. Gastric...
Injury can cause differentiated cells to undergo massive reprogramming to become proliferative to repair tissue via a cellular program called paligenosis. Gastric digestive-enzyme-secreting chief cells use paligenosis to reprogram into progenitor-like Spasmolytic-Polypeptide Expressing Metaplasia (SPEM) cells. Stage 1 of paligenosis is to downscale mature cell architecture via a process involving lysosomes. Here, we noticed that sulfated glycoproteins (which are metaplasia and cancer markers in mice and humans) were not digested during paligenosis but excreted into the gland lumen. Various genetic and pharmacological approaches showed that endoplasmic reticulum membranes and secretory granule cargo were also excreted and that the process proceeded in parallel with, but was independent lysosomal activity. 3-dimensional light and electron-microscopy demonstrated that excretion occurred via unique, complex, multi-chambered invaginations of the apical plasma membrane. As this lysosome-independent cell cleansing process does not seem to have been priorly described, we termed it "cathartocytosis". Cathartocytosis allows a cell to rapidly eject excess material (likely in times of extreme stress such as are induced by paligenosis) without waiting for autophagic and lysosomal digestion. We speculate the ejection of sulfated glycoproteins (likely mucins) would aid in downscaling and might also help bind and flush pathogens (like which causes SPEM) away from tissue.
PubMed: 38915707
DOI: 10.1101/2024.06.11.598489 -
Frontiers in Oncology 2024Homologous recombination (HR) comprises series of interrelated pathways that repair double-stranded DNA breaks and inter-strand crosslinks. It provides support for DNA...
The prognostic and predictive value of homologous recombination deficiency status in patients with advanced stage epithelial ovarian carcinoma after first-line platinum-based chemotherapy.
OBJECTIVE
Homologous recombination (HR) comprises series of interrelated pathways that repair double-stranded DNA breaks and inter-strand crosslinks. It provides support for DNA replication to recover stalled or broken replication forks. Compared with homologous recombination proficiency (HRP), cancers with homologous recombination deficiency (HRD) are more likely to undergo cell death when treated with DNA-damaging agents, such as platinum agents, and have better disease control.
METHODS
Patients diagnosed with stage III/IV ovarian cancer, early stages with recurrence, who received adjuvant chemotherapy after debulking surgery, and who also had known HR status were eligible.
RESULTS
Forty-four patients were included, with 21 in the HRD group (including 8 with germline mutations) and 23 in the HRP group. The HRD group was composed predominantly of serous carcinoma (95.2%), while mucinous (n=3) and clear cell (n=1) cases were all found in the HRP group. Stage III/IV disease was 66.7% and 91.3% in HRD and HRP groups, respectively (p=0.064). Patients who were optimally debulked to no residual disease was 90.0% and 72.7% (p=0.243), respectively. Late line use of PARP inhibitors was 33.3% and 17.4% (p=0.303). Median PFS was 22.5 months (95% CI, 18.5 - 66.6) and 21.5 months (95% CI, 18.3-39.5) (p=0.49) in HRD and HRP respectively. Median platinum free interval (PFI) was 15.8 months (95% CI 12.4-60.4) and 15.9 months (95% CI 8.3-34.1) (p=0.24), respectively. Median OS was 88.2 months (95% CI 71.2-NA) and 49.7 months (95% CI 35.1-NA) (p=0.21). The PFS of the patients with germline mutations (n=5) was 54.3 months (95% CI 23.1-NA) and 21.5 months (95% CI 18.3-39.5) in the HRP group (p=0.095); the PFI difference was 47.7 months (95% CI 17.6-NA) in the mutation group, and 15.9 months (95% CI 12.4-60.4) in HRP, showing statistical significance (p=0.039); while the median OS was NA and 49.7 months (95% CI 35.1-NA) respectively (p=0.051). When adding two additional patients with somatic mutations to the germline mutation carriers, the median OS is NA (95% CI 73, NA) versus 49.7 months (95% CI 35.1, NA) for HRP (p=0.045).
CONCLUSIONS
HRD status was not associated with longer PFS or PFI in advanced ovarian cancer who received first line adjuvant platinum-based chemotherapy. Its role as a prognostic marker for overall survival is suggested, particularly in the subgroup with germline and somatic mutations.
PubMed: 38915363
DOI: 10.3389/fonc.2024.1372482 -
Journal of Surgical Case Reports Jun 2024Mucoepidermoid carcinoma, a salivary gland tumor, rarely occurs in bronchial mucous glands. Brain metastases are rarely seen which makes for a challenging diagnosis and...
Mucoepidermoid carcinoma, a salivary gland tumor, rarely occurs in bronchial mucous glands. Brain metastases are rarely seen which makes for a challenging diagnosis and treatment approach. A 40-year-old woman presented with confusion, and ataxia, accompanied by a declining Glasgow Coma Score. Brain computerized tomography revealed two hyperdense, postcontrast-enhanced infra- and supratentorial lesions with perifocal edema. First causing obstructive hydrocephalus. The initial surgery involved external ventricular drainage system placement leading to the patient's clinical improvement. After radiological diagnostics, both lesions were resected without complications. Histopathological analysis revealed solid clusters of atypical, polygonal epithelial cells exhibiting mucin production, classified as a poorly differentiated mucoepidermoid carcinoma metastasis which originated from the upper lobe's apicoposterior segment and left lung. The correct treatment approach remains elusive due to the infrequent occurrence and challenging diagnosis. While new oncological and radiosurgery options promise improved overall survival rates, radical resection remains the preferred initial option.
PubMed: 38915342
DOI: 10.1093/jscr/rjae413 -
Human Genomics Jun 2024To investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. Methods...
Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence.
OBJECTIVE
To investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. Methods Genome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4).
RESULTS
A total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed.
CONCLUSION
This study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC.
Topics: Humans; Female; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Single-Cell Analysis; Genome-Wide Association Study; Alkaline Phosphatase; Biomarkers, Tumor; WAP Four-Disulfide Core Domain Protein 2; Aspartate Aminotransferases; Liver; Alanine Transaminase; gamma-Glutamyltransferase; CA-125 Antigen; Gene Expression Regulation, Neoplastic; Transcription Factors; Membrane Proteins; Middle Aged
PubMed: 38915066
DOI: 10.1186/s40246-024-00642-4 -
Journal of Medical Case Reports Jun 2024Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are...
BACKGROUND
Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.
CASE PRESENTATION
We report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.
CONCLUSION
Ovarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.
Topics: Humans; Female; Ovarian Neoplasms; Middle Aged; Carcinoid Tumor; Teratoma; Cystadenoma, Mucinous; Salpingo-oophorectomy; Hysterectomy; Treatment Outcome; Ultrasonography
PubMed: 38915051
DOI: 10.1186/s13256-024-04603-2 -
Microbiology Spectrum Jun 2024infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current...
infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current advances on phage-host studies. As a mucosal pathogen, we hypothesize that and its phages are linked to the bacteriophage adherence to mucus (BAM) model. This means that phage-host interactions could be influenced by mucin presence, impacting the success of phage infections on the host and consequently leading to the protection of the metazoan host. By using a group of four different phages, we tested three important phenotypes associated with the BAM model: phage binding to mucin, phage growth in mucin-exposed hosts, and the influence of mucin on CRISPR immunity of the bacterium. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. Improved phage growth was likely the result of phage exploitation of mucin-induced physiological changes in the host. We could not detect CRISPR activity in our system but identified two putative anti-CRISPR proteins coded by the phage. Overall, the differential responses seen for the phages tested show that the same bacterial species can be targeted by mucosal-associated phages or by phages not affected by mucus presence. In conclusion, the BAM model is relevant for phage-bacterium interactions in , opening new possibilities to improve phage therapy against this important pathogen by considering mucosal interaction dynamics.IMPORTANCESome bacteriophages are involved in a symbiotic relationship with animals, in which phages held in mucosal surfaces protect them from invading bacteria. is one of the many bacterial pathogens threatening humankind during the current antimicrobial resistance crisis. Here, we have tested whether and its phages are affected by mucosal conditions. We discovered by using a collection of four phages that, indeed, mucosal interaction dynamics can be seen in this model. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. These results link and its phages to the bacteriophage adherence to the mucus model and open opportunities to explore this to improve phage therapy, be it by exploiting the phenotypes detected or by actively selecting mucosal-adapted phages for treatment.
PubMed: 38912817
DOI: 10.1128/spectrum.03520-23 -
Frontiers in Oncology 2024Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid...
Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid surgery. We retrospectively searched for the patients with implants of thyroid tumor after surgery from our database prior to August 2023. The clinical and pathological data were reviewed. Six female patients with a mean age of 33.6 ± 13.3 years were enrolled in this study. There was a rare case with mucinous adenocarcinoma, three follicular thyroid carcinoma, and two papillary thyroid carcinoma. The case with primary enteric adenocarcinoma of thyroid with subcutaneous implantation was first reported. The patient with mucinous adenocarcinoma received six courses of TP regimen chemotherapy. Five cases received radioactive iodine therapy. After a mean of 69.5 months of follow-up, one case recurred in the lateral region, and no metastasis or recurrence happened in the other five cases. Although the implantation after thyroid surgery is uncommon, the cases serve as a reminder to take greater care to avoid implantation.
PubMed: 38912068
DOI: 10.3389/fonc.2024.1412466 -
Frontiers in Oncology 2024Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still...
Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.
PubMed: 38903727
DOI: 10.3389/fonc.2024.1387700 -
Frontiers in Immunology 2024Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune...
INTRODUCTION
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear.
OBJECTIVES
This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset.
METHODS
The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development.
RESULTS
B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag mice transplanted with fecal samples from -Cre mice showed delayed diabetes onset, indicating microbiota's impact.
CONCLUSION
B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.
Topics: Animals; Toll-Like Receptor 9; Gastrointestinal Microbiome; Mice, Inbred NOD; Interleukin-10; Mice; Diabetes Mellitus, Type 1; Mice, Knockout; B-Lymphocytes, Regulatory; Female; B-Lymphocytes
PubMed: 38903498
DOI: 10.3389/fimmu.2024.1413177