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Journal of Cancer 2024Chemoresistance is a key reason for treatment failure in colorectal cancer (CRC) patients. The tumor microenvironment of chemoresistant CRC is distinctly...
Chemoresistance is a key reason for treatment failure in colorectal cancer (CRC) patients. The tumor microenvironment of chemoresistant CRC is distinctly immunosuppressive, although the underlying mechanisms are unclear. The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method. The in-situ expression of transient receptor potential channel 5 (TRPC5) and fibroblast activation protein (FAP) in the CRC tissues was examined by immunohistochemistry. TRPC5 expression levels in the HCT8 and HCT116 cell lines and the corresponding 5-fluorouracil (5-FU)-resistant cell lines (HCT8R and HCT116R) were analyzed by western blotting and RT-PCR. Exosomes were isolated from the HCT8R and HCT116R cells and incubated with colorectal normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs)markers were detected. NFs were also incubated with exosomes isolated from TRPC5-knockdown HCT8R cells, and the changes in intracellular Ca levels and C-X-C motif chemokine ligand 12 (CXCL12) secretion were analyzed. TRPC5 and FAP expression showed positive correlation in the datasets. Immunostaining of CRC tissue specimens further revealed that high TRPC5 and FAP expressions were significantly associated with worse tumor regression. Furthermore, chemoresistant CRC cells expressed higher levels of TRPC5 compared to the chemosensitive cells, and knocking down TRPC5 reversed chemoresistance. Exosomes derived from CRC cells induced the transformation of NFs to CAFs. However, TRPC5-exosomes derived from chemoresistant CRC cells can promote CAFs to secrete more CXCL12. Chemoresistant CRC cells can induce CAFs activation and promote CXCL12 secretion through exosomal TRPC5.
PubMed: 38817851
DOI: 10.7150/jca.95248 -
Journal For Immunotherapy of Cancer May 2024The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been...
BACKGROUND
The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.
METHODS
This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.
RESULTS
A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3 DCs promote CD8 T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3 DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.
CONCLUSION
Our findings expound valuable insights into the role of the interaction between LAMP3 DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.
Topics: Humans; Dendritic Cells; Thyroid Cancer, Papillary; Lysosomal-Associated Membrane Protein 3; Thyroid Neoplasms; Male; Female; Tumor Microenvironment; Middle Aged; Tumor Escape; T-Lymphocyte Subsets; Neoplasm Proteins
PubMed: 38816233
DOI: 10.1136/jitc-2024-008983 -
Turkish Journal of Medical Sciences 2023To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
BACKGROUND/AIM
To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
MATERIALS AND METHODS
Herein, 6 equal groups of rats were formed (n: 48): control group, sham group, torsion/detorsion (T/D)-1 h group, T/D-1 h + ASA group, T/D-8 h group, and T/D-8 h + ASA group. Testicular torsion was created by rotating the left testis 720° clockwise. At 30 min before torsion, 100 mg/kg of ASA was injected intraperitoneally. Elastography was performed at 8 and 24 h. After orchiectomy, specimens were collected for histopathological evaluation.
RESULTS
When comparing the left testicular volume (LV) parameters obtained from the elastography applied at 8 h, significant differences were observed between the following group pairs: the sham and T/D-8 h groups, T/D-1 h and T/D-8 h groups, and T/D-1 h + ASA and T/D-8 h groups (p = 0.004, p = 0.023, and p = 0.026, respectively). The mean LVS (velocity) (stiffness assessment) of the groups was similar at 8 h. When comparing the LV parameters at 24 h, significant differences were found between the T/D-1 h and T/D-8 h groups and between the T/D-8 h and T/D-8 h + ASA groups (p = 0.008 and p = 0.004, respectively). For the LVS mean values at 24 h, significant differences were found between the control and sham groups, sham and T/D-1 h groups, sham and T/D-8 h groups, and sham and T/D-8 h + ASA groups (p = 0.009, p = 0.021, p = 0.027, and p = 0.009, respectively).Histopathological evaluation showed a decrease in the morphological grades and an increase in the mean testicular injury scores in the T/D-1 h + ASA group compared to the T/D-1 h group. The T/D-8 h + ASA group had a higher morphological grade than the T/D-8 h group, whereas their mean testicular injury scores were similar.
CONCLUSION
ASA treatment for testicular torsion was shown to be ineffective. Elastography can be a complementary method to Doppler ultrasonography in the diagnosis of testicular torsion and can guide surgeons in their approach to surgery.
Topics: Male; Spermatic Cord Torsion; Animals; Aspirin; Elasticity Imaging Techniques; Rats; Testis; Disease Models, Animal; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38813515
DOI: 10.55730/1300-0144.5729 -
Journal of Taibah University Medical... Jun 2024Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs)...
BACKGROUND
Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs) are associated with most non-Hodgkin lymphomas. Non-coding microRNAs (miRNAs) greatly affect gene expression. A single miRNA can target numerous genes, thus largely influencing gene expression networks. MiRNAs can act as oncogenes or tumor suppressors in controlling DLBCL progression. This study investigated the roles of miRNAs in patients with DLBCL through next-generation sequencing, which was found to be sensitive, accurate, and robust.
METHODS
The study involved seven patients with DLBCLs and three controls at a hematology-oncology clinic. MiRNA was extracted from existing formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Illumina next-generation sequencing was used to sequence samples for miRNA profiling.
RESULTS
Samples from patients showed expression of various hsa-mir miRNAs (1248, 3607, 21, 142, 1244, 182, 6516, 766, 1291, 4449, and 181a), whereas those from healthy individuals showed expression of hsa-mir 1248, 3607, 21, 142, and 877. Hsa-mir-877-3p is known to target multiple genes, and miRNAs such as hsa-mir-877-3p, hsa-mir-1291, and hsa-mir-181a-5p interact primarily with target genes.
CONCLUSIONS
MiRNA profiling in FFPE tissues from patients with DLBCL suggested that miRNA levels can distinguish patients with DLBCL from controls, and therefore may provide prognostic or diagnostic biomarkers for DLBCL. Altered genes and miRNAs may also be potential therapeutic targets.
PubMed: 38812724
DOI: 10.1016/j.jtumed.2024.04.010 -
Turkish Journal of Medical Sciences 2024Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on...
BACKGROUND/AIM
Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated.
MATERIALS AND METHODS
Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral gavage technique, the glutamine group was ingested with 200 mg/kg/day of glutamine, and the omega-3 group was ingested with 100 mg/kg/day of omega-3 fatty acids. At the end of 14 days, the rats were euthanized, blood specimens were collected, and intestinal segments, including serosal patches, were excised.
RESULTS
Transforming growth factor-beta was significantly lower in the glutamine group compared to the control group. Similarly, fibroblast growth factor-2 was significantly lower in the glutamine group compared to the sham group. Intestinal neomucosa formation was observed in 100% of rats in the glutamine group. In the control and omega-3 groups, intestinal neomucosa formation was observed in 57.1% and 60% of rats, respectively. The inflammatory response, granulation tissue formation, and fibroblastic activity were more severe in the rats of the glutamine and omega-3 groups.
CONCLUSION
The intestinal neomucosa formation is an experimental technique, and both glutamine and omega-3 fatty acids have the potential to positively affect inflammatory response, granulation tissue formation, and fibroblastic activity. Specifically, glutamine has a favorable effect on intestinal neomucosa formation.
Topics: Animals; Glutamine; Fatty Acids, Omega-3; Rats, Sprague-Dawley; Male; Rats; Colon; Short Bowel Syndrome; Serous Membrane; Intestinal Mucosa
PubMed: 38812652
DOI: 10.55730/1300-0144.5766 -
Radiology Case Reports Aug 2024Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid...
Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid masses. A premenopausal woman in her 50s was referred to our hospital because of an increasing watery vaginal discharge. A multifocal cyst measuring 5 × 4.5 cm in size projecting into the endocervical canal was revealed on a contrast-enhanced MRI. The fluid within the tumor showed a hypointense signal on T1-weighted imaging (T1WI) and a hyperintense signal on T2-weighted imaging (T2WI). On T2WI, most of the septa within the tumor showed a slightly hyperintense to hypointense signal, whereas some areas revealed a strong hypointense signal; the contrast effect on the septum was satisfactory. On the T2WI taken 2 years previously, the tumor was a 4.5 × 3.5 cm polypoid mass protruding from the posterior endocervical wall. Contrastingly, the current T2WI showed that the stem was no longer identifiable because of tumor growth. Because previous imaging showed that the tumor was a stalked tumor protruding from the posterior endocervical wall, the imaging diagnosis was uterine adenomyoma of the endocervical type. A biopsy suggested the possibility of a minimal deviation adenocarcinoma (MDA). Hence, a total hysterectomy was performed. The final diagnosis confirmed the uterine adenomyoma of endocervical type. Uterine adenomyoma of the endocervical type might be difficult to differentiate from MDA in small biopsy specimens; therefore, evaluation of morphology by MRI is considered important in preoperative diagnosis.
PubMed: 38812595
DOI: 10.1016/j.radcr.2024.04.084 -
Dermatology Practical & Conceptual Apr 2024Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have...
Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.
INTRODUCTION
Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs).
OBJECTIVES
The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC.
METHODS
Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement.
RESULTS
The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724).
CONCLUSIONS
The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.
PubMed: 38810079
DOI: 10.5826/dpc.1402a90 -
PloS One 2024Recently, a low-level somatic mutation in the NRAS gene (c.182 A > G, Q61R) was identified in various specimens from patients with kaposiform lymphangiomatosis. However,...
Recently, a low-level somatic mutation in the NRAS gene (c.182 A > G, Q61R) was identified in various specimens from patients with kaposiform lymphangiomatosis. However, it is unknown how these low-frequency mutated cells can affect the characterization and surrounding environment of their lesions. To understand the pathogenesis and association of these gene abnormalities, we established NRASQ61R mutated lymphatic endothelial cells transfected with lentivirus vector and undertook morphological and functional characterization, protein expression profiling, and metabolome analysis. NRASQ61R human dermal lymphatic endothelial cells showed poor tube formation, a low proliferation rate, and high migration ability, with an increase in the ratio of mutated cells. An analysis of signaling pathways showed inactivation of the PIK3/AKT/mTOR pathway and hyperactivation of the RAS/MAPK/ERK pathway, which was improved by MAPK kinase (MEK) inhibitor treatment. This study shows the theoretical circumstances induced in vitro by NRASQ61R-mutated cells in the affected lesions of kaposiform lymphangiomatosis patients.
Topics: Humans; Endothelial Cells; GTP Phosphohydrolases; Membrane Proteins; Mutation; Cell Proliferation; Signal Transduction; Cell Movement; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt
PubMed: 38809881
DOI: 10.1371/journal.pone.0289187 -
Asian Pacific Journal of Cancer... May 2024Mongolia faces a significant burden of cervical cancer, with the highest prevalence of Human Papillomavirus (HPV) in the region. Cervical cancer ranks as the third most...
BACKGROUND
Mongolia faces a significant burden of cervical cancer, with the highest prevalence of Human Papillomavirus (HPV) in the region. Cervical cancer ranks as the third most common cancer among women in the country. This study aimed to assess the acceptance of self-sampling among young women in Mongolia and evaluate their knowledge regarding HPV and cervical cancer.
METHODS
In this study, participants provided a self-administered vaginal swabs to detect high-risk HPV genotypes. Both acceptability of self-sampling using swabs and participants knowledge regarding HPV and cervical cancer through a scored questionnaire were assessed. The knowledge scale was categorized into three groups: low (0-2), moderate (3-4) and high (5-6).
RESULTS
A total of 203 women aged 24-28 years completed the questionnaire and provided self-administered vaginal swabs. The majority (95.1%) found self-sampling technique using Copan Self Vaginal FLOQSwabs® easy to perform. Additionally, 98.5% indicated that the self-swab instructions were clear and comprehensive, while 94.1% reported no pain during the process. Furthermore, 67.8% of participants expressed a preference for performing the swab in a clinic rather than at home. All respondents chose self-sampling due to greater personal privacy, tranquility, reduced anxiety and time optimization. The questionnaire results revealed an overall low level of knowledge about HPV among participants, with a mean score at 1.9 out of 6 [95%CI 1.67-2.21] and a moderate level of knowledge regarding cervical cancer risks, with a mean score at 3.7 out of 6 [95%CI 3.19-4.21]. This pattern was consistent across both vaccinated and unvaccinated cohorts, indicating a strong demand for enhanced awareness of HPV and cervical cancer.
CONCLUSIONS
This study demonstrates the high acceptance of self-sampling among young women aged 24-28 years in Mongolia. However, it also underscores a significant need for improved awareness initiatives concerning HPV and cervical cancer in Mongolia.
Topics: Humans; Female; Papillomavirus Infections; Adult; Mongolia; Young Adult; Health Knowledge, Attitudes, Practice; Uterine Cervical Neoplasms; Papillomaviridae; Surveys and Questionnaires; Vaginal Smears; Self Care; Follow-Up Studies; Specimen Handling; Patient Acceptance of Health Care; Prognosis; Early Detection of Cancer; Cross-Sectional Studies; Human Papillomavirus Viruses
PubMed: 38809655
DOI: 10.31557/APJCP.2024.25.5.1823 -
Asian Pacific Journal of Cancer... May 2024Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited...
OBJECTIVE
Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited efficacy in prolonging survival rates. This study aimed to assess the anticancer properties of Aaptos suberitoides extracts and fraction on the U87 cell line, serving as a representative model for GBM.
METHODS
U87 cells were treated with ethanol extracts derived from Aaptos suberitoides, specifically two extracts (OAA-1 and OAA-2) and one ethyl acetate fraction (EA) isolated from specimens collected on Pramuka Island and Tinjil Island. The evaluation encompased microscopic observation and MTT assay to determine the IC50. Subsequently, antiproliferative effects were investigated through apoptosis and cell cycle assays.
RESULTS
The extract demonstrated cytotoxic activity against U87 cells, with OAA-1 and OAA-2 exhibiting IC50 values of 35.78 μg/mL and 25.38 μg/mL, respectively. OAA-1 notably induced apoptosis at 50 μg/mL and induced cell cycle arrest. On other hand, OAA-2, while also inducing apoptosis significantly, had a lesser impact on cell cycle arrest. In contrast, EA induced significant apoptosis at a concentration of 100 μg/mL.
CONCLUSION
The ethanol extracts and the ethyl acetate fraction of Aaptos suberitoides emerged as a promising candidate for Glioblastoma Multiforme cancer therapy, showing potential in inhibiting cell proliferation and inducing apoptosis.
Topics: Humans; Glioblastoma; Apoptosis; Cell Proliferation; Plant Extracts; Tumor Cells, Cultured; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Brain Neoplasms
PubMed: 38809654
DOI: 10.31557/APJCP.2024.25.5.1815