-
BMC Nephrology Jun 2024To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody...
OBJECTIVE
To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody associated vasculitis (MPO-AAV) rats.
METHODS
Thirty Wistar-Kyoto (WKY) rats were randomly divided into: Control group, MPO-AAV group (400 µg/kg MPO mixed with Freund's complete adjuvant i.p), MPO-AAV + Anti-FKN group (400 µg/kg MPO mixed with Freund's complete adjuvant i.p), anti-FKN group (1 µg/ rat /day, i.p) after 6 weeks. MPO-AAV associated glomerulonephritis model was established by intraperitoneal injection of MPO + Freund's complete adjuvant with 10 mice in each group. The concentration of MPO-ANCA and FKN in serum was detected by Enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to detect pathological changes of kidney tissue. Western blot and immunofluorescence staining were used to detect the expression and localization of FKN protein in kidney tissue. Renal function test indicators: 24-hour urinary protein (UAER), blood urea nitrogen (BUN), serum creatinine (Scr). The expression levels of p65NF-κB and IL-6 was detected by Immunohistochemical assays.
RESULTS
Compared with the control group, the serum MPO-ANCA antibody expression level in the MPO-AAV group was significantly increased (P < 0.01), and the contents of UAER, BUN and Scr were significantly up-regulated at 24 h (P < 0.01). Compared with the control group, the glomeruli in the MPO-AAV group had different degrees of damage, infiltration of inflammatory cell, and membrane cell hyperplasia and renal tubule edema. Compared with the control group, rats in the MPO-AAV group had significantly higher levels of FKN in serum and renal tissues (P < 0.01), and high expression of p65NF-κB and IL-6 in renal tissues (P < 0.01) (P < 0.05), whereas anti-FKN reversed the expression of the above factors. In MPO-AAV renal tissue, FKN was mainly expressed in the cytoplasm of renal tubular epithelial cells and glomerular podocytes. In addition, the contents of 24 h UAER, BUN and Scr of renal function in MPO-AAV rats were significantly decreased (P < 0.01) and the damage of renal tissue was significantly ameliorated after the administration of antagonistic FKN.
CONCLUSION
FKN may play a key role in the pathogenesis of MPO-AAV associated glomerulonephritis.
Topics: Animals; Chemokine CX3CL1; Glomerulonephritis; Rats; Peroxidase; Rats, Inbred WKY; Male; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Kidney; Antibodies, Antineutrophil Cytoplasmic; Transcription Factor RelA
PubMed: 38937701
DOI: 10.1186/s12882-024-03565-3 -
International Journal of Hyperthermia :... 2024The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the...
BACKGROUND
The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).
METHOD
All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses.
RESULTS
In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses.
CONCLUSION
OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.
Topics: Humans; Pseudomyxoma Peritonei; Male; Female; Colorectal Neoplasms; Peritoneal Neoplasms; Middle Aged; Omentum; Aged; Adult; Hyperthermic Intraperitoneal Chemotherapy; Cytoreduction Surgical Procedures; Aged, 80 and over
PubMed: 38937059
DOI: 10.1080/02656736.2024.2372356 -
The Kobe Journal of Medical Sciences Jun 2024Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A...
Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A 62 years-old male had a tumor in the nasal cavity and diagnosed as ONB with Kadish A stage. Anterior skull base surgery was performed as radical treatment. Since the surgical margin was negative, no postoperative radiotherapy was administered. 14 years after the surgery, bilateral otitis media with effusion (OME) was occurred, we found the recurrence tumor at bilateral retropharyngeal lymph node (RPLN) which surrounded the internal carotid arteries. Since these were unresectable, we planned chemoradiotherapy which was 70Gy of intensity modulated radiotherapy combined with two courses of carboplatin and etoposide. The tumor volume was reduced and bilateral OME were improved. He has been alive for 3 years after salvage treatment. Although ONB has a relatively good prognosis, it is known to often cause cervical lymph node metastasis. Grades III and IV of Hyams classification are considered high risk. This case, initial tumor was limited in the nasal cavity and its clinical classification was early stage, but Hyams classification was grade III. In reference to this case, considering that RPLN metastasis are difficult to radically resect at the salvage surgery, including this area in postoperative radiotherapy was considered an option.
Topics: Humans; Male; Esthesioneuroblastoma, Olfactory; Middle Aged; Lymphatic Metastasis; Nose Neoplasms; Nasal Cavity; Skull Base; Neoplasm Recurrence, Local; Chemoradiotherapy
PubMed: 38936878
DOI: 10.24546/0100489917 -
American Society of Clinical Oncology... Jun 2024The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen... (Review)
Review
The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen deprivation therapy to an era of advanced imaging, precision diagnostics, genomics, and targeted treatment options. Concurrently, the emergence of large language models (LLMs) has dramatically transformed the paradigm for artificial intelligence (AI). This convergence of advancements in prostate cancer management and AI provides a compelling rationale to comprehensively review the current state of AI applications in prostate cancer care. Here, we review the advancements in AI-driven applications across the continuum of the journey of a patient with prostate cancer from early interception to survivorship care. We subsequently discuss the role of AI in prostate cancer drug discovery, clinical trials, and clinical practice guidelines. In the localized disease setting, deep learning models demonstrated impressive performance in detecting and grading prostate cancer using imaging and pathology data. For biochemically recurrent diseases, machine learning approaches are being tested for improved risk stratification and treatment decisions. In advanced prostate cancer, deep learning can potentially improve prognostication and assist in clinical decision making. Furthermore, LLMs are poised to revolutionize information summarization and extraction, clinical trial design and operations, drug development, evidence synthesis, and clinical practice guidelines. Synergistic integration of multimodal data integration and human-AI integration are emerging as a key strategy to unlock the full potential of AI in prostate cancer care.
Topics: Humans; Male; Prostatic Neoplasms; Artificial Intelligence
PubMed: 38935882
DOI: 10.1200/EDBK_438516 -
PloS One 2024Lung cancer is one of the most common and deadliest cancers. Preclinical models are essential to study new therapies and combinations taking tumor genetics into account....
Lung cancer is one of the most common and deadliest cancers. Preclinical models are essential to study new therapies and combinations taking tumor genetics into account. We have established cell lines expressing the luciferase gene from lines with varied genetic backgrounds, commonly encountered in patients with pulmonary adenocarcinoma. We have characterized these lines by testing their response to multiple drugs. Thus, we have developed orthotopic preclinical mouse models of NSCLC with very high engraftment efficiency. These models allow the easy monitoring of tumor growth, particularly in response to treatment, and of tumor cells dissemination in the body. We show that concomitant treatment with osimertinib (3rd generation tyrosine kinase inhibitor targeting mutated EGFR) and bevacizumab (anti-angiogenic targeting VEGF) can have a beneficial therapeutic effect on EGFR-mutated tumors. We also show that the addition of afatinib to osimertinib-treated tumors in escape leads to tumor growth inhibition. No such effect is observed with selumetinib or simvastatin. These preclinical mouse models therefore make it possible to test innovative therapeutic combinations and are also a tool of choice for studying resistance mechanisms.
Topics: Animals; Aniline Compounds; Acrylamides; Afatinib; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mice; Humans; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Disease Models, Animal; Xenograft Model Antitumor Assays; ErbB Receptors; Quinazolines; Piperazines; Female; Indoles; Pyrimidines
PubMed: 38935790
DOI: 10.1371/journal.pone.0304914 -
PloS One 2024
Topics: Animals; Frontotemporal Dementia; Mice; Humans; tau Proteins; Mutation; Genotype; Cell Line; Central Nervous System
PubMed: 38935762
DOI: 10.1371/journal.pone.0305843 -
PloS One 2024Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer...
Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.
Topics: Humans; Colorectal Neoplasms; Snail Family Transcription Factors; Cell Adhesion Molecules; Prognosis; Female; Male; Middle Aged; Carrier Proteins; Microfilament Proteins; Epithelial-Mesenchymal Transition; Aged; Biomarkers, Tumor; Adult; Cadherins; Transcription Factors; beta Catenin; Aged, 80 and over; Periostin
PubMed: 38935747
DOI: 10.1371/journal.pone.0304666 -
PloS One 2024Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing... (Observational Study)
Observational Study
Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE.
Topics: Humans; Female; Endometritis; Hysteroscopy; Adult; Endometrium; Retrospective Studies; Chronic Disease; Biopsy; Middle Aged
PubMed: 38935687
DOI: 10.1371/journal.pone.0303041 -
PloS One 2024Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates...
Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.
OBJECTIVES
Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.
METHODS/MATERIALS
This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed.
RESULTS
Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).
CONCLUSIONS
In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.
Topics: Humans; Female; Endometrial Neoplasms; Myometrium; Middle Aged; Adult; Republic of Korea; Neoplasm Invasiveness; Neoplasm Grading; Prospective Studies; Aged; Preoperative Period; Magnetic Resonance Imaging; Carcinoma, Endometrioid
PubMed: 38935680
DOI: 10.1371/journal.pone.0305360 -
PloS One 2024Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These...
Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.
Topics: Humans; Female; Colombia; Breast Neoplasms; Middle Aged; Adult; Health Status Disparities; White People; Aged; Socioeconomic Factors
PubMed: 38935662
DOI: 10.1371/journal.pone.0306037