-
Acta Dermatovenerologica Alpina,... Jun 2024This study explores the immunogenetic associations of human leukocyte antigens (HLA) and the calcium release-activated calcium modulator 1 (ORAI1) and stromal...
INTRODUCTION
This study explores the immunogenetic associations of human leukocyte antigens (HLA) and the calcium release-activated calcium modulator 1 (ORAI1) and stromal interaction molecule 1 (STIM1) genes in HIV-1‒positive patients with HIV-related skin disorders.
METHODS
This study assessed the distribution of variants of HLA class II alleles and expression levels of ORAI1 and STIM1 genes in the blood between HIV-1‒positive patients with HIV-related skin disorders and the control group with no HIV within the Latvian population.
RESULTS
The research group comprised 115 HIV-1‒positive patients with HIV-related skin disorders, and the control group included 80 healthy individuals. Risk alleles (HLA- DQB1*02:01-0301 and HLA-DQA1*01:01-0501) and protective alleles (HLA-DRB1*07-13, DRB1*01-13, DRB1*04-11, and HLA-DQA1*05:01-0501) showed statistical significance in the groups. In 38 out of 115 patients, higher expression levels of ORAI1 and STIM1 genes were detected in the blood at the beginning of treatment. A significantly higher level of the microribonucleic acid (mRNA) ORAI1 gene was also found in the control group.
CONCLUSIONS
The results demonstrate that HLA class II alleles are associated with a trend toward risk/protection concerning HIV-related skin disorders in HIV-1‒positive patients. It was also shown that a low level of ORAI1 mRNA and the risk allele HLA-DQB1*0201-0301 were simultaneously present in the research group.
Topics: Humans; ORAI1 Protein; Male; Latvia; Female; Stromal Interaction Molecule 1; Adult; HIV Infections; Middle Aged; Polymorphism, Genetic; Skin Diseases; Case-Control Studies; Neoplasm Proteins; Genetic Predisposition to Disease
PubMed: 38918943
DOI: No ID Found -
Asian Pacific Journal of Cancer... Jun 2024Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is its many immune cells called tumor-infiltrating lymphocytes (TILs). Recent studies have suggested that TILs in many types of cancer can indicate a better prognosis. However, the role of TILs in NPC is still a matter of debate. Further research is necessary to determine whether TILs can be used as a prognostic factor of NPC's outcome.
METHOD
A retrospective cohort study was conducted at Sardjito Hospital to examine the records and pathological sections of patients treated for the undifferentiated subtype of NPC. Two pathologists analyzed the presence of TILs using HE-stained slides. TILs were evaluated in stromal compartments, and their association with clinicopathological variables was analyzed using the Chi-square and Fisher exact tests. The study compared overall survival in tumor patients with varying TIL levels using Kaplan-Meier survival curves and the log-rank test. A Cox regression model was used for univariate and multivariate analyses to test the significance of different factors.
RESULT
Out of the total 61 subjects, 16 (26.2%) had high stromal TILs (≥ 70%), and 45 (73.8%) had low stromal TILs (<70%). The subjects' sex, age, and tumor stage did not affect the OS. However, high stromal TILs (≥ 70%) showed a significant association with a longer OS (log-rank test p = 0.006, HR 0.37, 95% CI 0.17-0.79, log-rank p = 0.006). Moreover, multivariate analysis confirmed that TILs were an independent prognostic indicator for OS (aHR 0.015).
CONCLUSION
TILs correlate positively with overall survival in the undifferentiated NPC subtype and are an independent prognostic indicator.
Topics: Humans; Lymphocytes, Tumor-Infiltrating; Male; Female; Prognosis; Retrospective Studies; Nasopharyngeal Neoplasms; Middle Aged; Nasopharyngeal Carcinoma; Survival Rate; Adult; Carcinoma; Follow-Up Studies; Aged; Neoplasm Staging
PubMed: 38918661
DOI: 10.31557/APJCP.2024.25.6.1997 -
Medical Oncology (Northwood, London,... Jun 2024Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an incurable disease. GBM has a poor prognosis with a median survival of 12-15 months, and its aggressive clinical course is related to rapid growth, extensive infiltration of adjacent tissues, resistance to chemotherapy, radiotherapy and immunotherapy, and frequent relapse. Currently, several molecular biomarkers are used in clinical practice to predict patient prognosis and response to treatment. However, due to the overall unsatisfactory efficacy of standard multimodal treatment and the remaining poor prognosis, there is an urgent need for new biomarkers and therapeutic strategies for GBM. Recent evidence suggests that GBM tumorigenesis is associated with crosstalk between cancer, immune and stromal cells mediated by various cytokines. One of the key factors involved in this process appears to be interleukin-17 (IL-17), a pro-inflammatory cytokine that is significantly upregulated in the serum and tissue of GBM patients. IL-17 plays a key role in tumorigenesis, angiogenesis, and recurrence of GBM by activating pro-oncogenic signaling pathways and promoting cell survival, proliferation, and invasion. IL-17 facilitates the immunomodulation of the tumor microenvironment by promoting immune cells infiltration and cytokine secretion. In this article we review the latest scientific reports to provide an update on the role of IL-17 role in tumorigenesis, tumor microenvironment, diagnosis, prognosis, and treatment of GBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Interleukin-17; Tumor Microenvironment; Biomarkers, Tumor; Prognosis
PubMed: 38918274
DOI: 10.1007/s12032-024-02434-1 -
Rhode Island Medical Journal (2013) Jul 2024Syringocystadenoma papilliferum (SCAP) is a benign adnexal tumor commonly found on the scalp and face, and often associated with nevus sebaceous, with about half of...
Syringocystadenoma papilliferum (SCAP) is a benign adnexal tumor commonly found on the scalp and face, and often associated with nevus sebaceous, with about half of cases appearing in early childhood. SCAP exhibits cystic invaginations with papillary structures and a double-layered glandular epithelium linked to the epidermal surface and stromal plasma cells. We are reporting a rare instance of intradermal SCAP in a 55-year-old male. He sought evaluation for a long-standing asymptomatic dark-pink papule in his left popliteal fossa, measuring 0.7 x 0.5 x 0.4 cm. A shave biopsy revealed papillary dermal fibrosis, glandular epithelium with apocrine secretion, and papillary projections without an epidermal connection. Infundibulofollicular keratinization was observed, along with stromal plasma cells. The patient chose local excision as the treatment option. This case highlights the rarity of intradermal SCAP, especially in the left popliteal fossa, with only one other reported case in the literature.
Topics: Humans; Male; Middle Aged; Sweat Gland Neoplasms; Tubular Sweat Gland Adenomas; Biopsy
PubMed: 38917308
DOI: No ID Found -
European Journal of Endocrinology Jun 2024Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal...
Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for two index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome.
PubMed: 38917055
DOI: 10.1093/ejendo/lvae075 -
Journal of Cancer Research and Clinical... Jun 2024Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the...
PURPOSE
Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.
METHODS
873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software.
RESULTS
The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE.
CONCLUSION
This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemokine CCL17; Female; Male; Prognosis; Receptors, CCR4; Middle Aged; Biomarkers, Tumor; 5'-Nucleotidase; Retrospective Studies; Tumor Microenvironment; GPI-Linked Proteins; Aged; Adult
PubMed: 38914802
DOI: 10.1007/s00432-024-05832-0 -
Journal of Applied Biomedicine Jun 2024Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl...
Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.
Topics: Pyruvates; Lymphoma, Large B-Cell, Diffuse; Humans; Animals; Cell Adhesion; Cell Proliferation; Cell Line, Tumor; Mice; Apoptosis; Proto-Oncogene Proteins c-jun; Xenograft Model Antitumor Assays
PubMed: 38912866
DOI: 10.32725/jab.2024.014 -
International Journal of Nanomedicine 2024The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately... (Review)
Review
The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy.
Topics: Tumor Microenvironment; Humans; Neoplasms; Nanoparticles; Drug Delivery Systems; Antineoplastic Agents; Animals; Hydrogen-Ion Concentration
PubMed: 38911497
DOI: 10.2147/IJN.S459710 -
Archives of Gynecology and Obstetrics Jun 2024Sclerosing stromal tumors (SST) are rare ovarian neoplasms that often appear as solid unilateral tumors of the ovary with no specific clinical or radiological...
BACKGROUND
Sclerosing stromal tumors (SST) are rare ovarian neoplasms that often appear as solid unilateral tumors of the ovary with no specific clinical or radiological presentation. The definitive treatment is surgical removal.
CASE PRESENTATION
Our article presents four cases of female patients with sclerosing stromal ovarian tumor with clinical characteristics mimicking malignant ovarian lesions. Interestingly, two of our cases had elevated levels of inhibin B. All patients were treated with surgery (oophorectomy) and had no disease recurrence.
CONCLUSION
Tumors' macroscopic features are usually non-specific and often suggestive of possible malignancy, therefore diagnosis is always based on histopathological report.
PubMed: 38910143
DOI: 10.1007/s00404-024-07520-3 -
BMC Women's Health Jun 2024This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior...
BACKGROUND
This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery.
MATERIALS AND METHODS
This is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution's local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed.
RESULTS
Totally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63-21.25; p = 0.07).
CONCLUSIONS
NACT shouldn't be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).
Topics: Humans; Female; Uterine Cervical Neoplasms; Neoadjuvant Therapy; Middle Aged; Carcinoma, Squamous Cell; Hysterectomy; Neoplasm Staging; Adult; Chemotherapy, Adjuvant; Aged; Retrospective Studies; Disease-Free Survival
PubMed: 38909186
DOI: 10.1186/s12905-024-03215-8