scholarly journals Targeting the Tumor Immune Microenvironment Could Become a Potential Therapeutic Modality for Invasive Pituitary Adenoma.

2021 ◽  
Author(s):  
Zuocheng Yang ◽  
Xuemei Tian ◽  
Chen Wang ◽  
Kun Yao ◽  
Yakun Yang ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Therapeutic Modality ◽  
Treatment Modalities ◽  
Ki 67 ◽  
P53 Expression ◽  
Mgmt Expression ◽  
Multiple Treatment ◽  
Positive Correlations

Abstract Objective: The study aimed to explore the relationship between the invasiveness and immune cell infiltration in pituitary adenoma (PA) and provide the basis for immuno-targeting therapies.Methods: One hundred three patients who underwent surgery at a single institution were retrospectively identified. The infiltration of macrophages and T lymphocytes was quantitatively assessed in PA.Results: The number of CD68+ macrophages was positively correlated with Knosp (P=0.003) and MMP-9 grades (P=0.00). The infiltration of CD163+ macrophages differed among Knosp (P=0.022) and MMP-9 grades (P=0.04). CD8+ tumor-infiltrating lymphocytes (TILs) were also positively associated with Knosp (P=0.002) and MMP-9 grades (P=0.01). Interestingly, MGMT expression was positively correlated with MMP-9 staining extent (P=0.000). The quantity of CD8+ TILs (P= 0.016), CD68+ macrophages (P=0.000) and CD163+ macrophages (P=0.043) were negatively associated with MGMT expression levels. The number of CD68+ macrophages in the PD-L1 negative group was significantly more than in the PD-L1 positive group (P=0.01). The rate of PD-L1 positivity had positive correlations with the Ki-67 index (P=0.046) and p53 expression (P =0.029). Conclusion: Targeted therapy for macrophages and CD8+ TILs could be a helpful treatment in the future for invasive PA. Temozolomide (TMZ) may have better effects on the treatment of PA infiltrating more immune cells. Anti-PD-L1 therapy may better respond to PA with higher Ki-67, p53 expression and more infiltrating CD68+ macrophages. Multiple treatment modalities, especially combined immunotherapy, or immunotherapy with TMZ combination, could become a novel therapeutic strategy for invasive PA.

scholarly journals P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Marjory Alana Marcello ◽  
Elaine Cristina Morari ◽  
Lucas Leite Cunha ◽  
Aline Carolina De Nadai Silva ◽  
Dirce Maria Carraro ◽  
...  
Keyword(s):  
Immune Cell ◽  
Profile Analysis ◽  
Early Stage ◽  
P53 Protein ◽  
Cell Activity ◽  
Tumor Infiltrating Lymphocytes ◽  
Cytotoxic T Cell ◽  
P53 Expression ◽  
Cell Markers ◽  
Normal Tissues

Background. Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC).Methods. ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also,TP53was sequenced in 78 out of 164 patients with papillary thyroid carcinoma.Results. P53 expression was observed more frequently in malignant than in benign lesions (P<0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller (P=0.0015), unique tumors (P=0.0286), with thyroiditis (P=0.0486) and without metastasis at diagnosis (P=0.0201). TAM was more frequent in P53 negative tumors (P=0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC (P<0.001).Conclusions. We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.

scholarly journals Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 243
Author(s):  
Ashish Kothari ◽  
Vanya Singh ◽  
Uttam Kumar Nath ◽  
Sandeep Kumar ◽  
Vineeta Rai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Performance ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Antigen Receptors ◽  
Multiple Treatment ◽  
Global Pandemic ◽  
Treatment Plans

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials and their respective outcomes for blocking SARS-CoV-2 pathogenesis through regenerative medicine, such as stem cell therapy, chimeric antigen receptors, natural killer (NK) cells, extracellular vesicular-based therapy, and others including immunomodulatory regimens, anti-neoplastic therapy, and current clinical vaccine therapy.

scholarly journals Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Clarissa Groberio Borba ◽  
Rafael Loch Batista ◽  
Nina Rosa de Castro Musolino ◽  
Vanielle Carvalho Machado ◽  
Ana Elisa Evangelista Alcantara ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Carcinoma ◽  
Cushing's Disease ◽  
Resonance Imaging ◽  
Ki 67 ◽  
P53 Expression ◽  
Acth Secreting ◽  
Pituitary Carcinomas

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

scholarly journals The expression and significance of p53 protein and Ki-67 protein in pterygium

2016 ◽  
Vol 73 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Vesna Ljubojevic ◽  
Radoslav Gajanin ◽  
Ljiljana Amidzic ◽  
Zoran Vujkovic
Keyword(s):  
P53 Protein ◽  
Tissue Growth ◽  
Ki 67 ◽  
P53 Expression ◽  
Factors Affecting ◽  
Gender And Age ◽  
Study Support ◽  
Positive Correlations ◽  
The Relationship ◽  
Growth Disorder

Background/Aim. Pterygium is considered to be a degenerative disease of the conjunctiva, however, the presence of tumor markers in pterygium reinforces the hypothesis that this lesion is similar to tumor. Inactivation of p53 function removes an obstacle to increased proliferation. Factors affecting the prevalence of p53 expression in pterygium deserve investigation. The aim of the study was to investigate the expression of p53 and Ki-67 proteins in pterygium and normal conjunctiva, the effects of gender and age on p53 expression, and the relationship between the expression of p53 and Ki-67 proteins. Methods. A total of 34 samples of pterygium and 34 samples of the normal conjunctiva were analyzed. The samples were studied by immunohistochemistry using antibodies against p53 and Ki-67. Results. Totally 15 (44%) samples of pterygia were p53 positive. Correlations between the expression of p53 protein and sex, and age were not established. The number of Ki-67 positive cells in pterygium (9.74%) was significantly higher than the number of Ki-67 positive cells in the normal conjunctiva (1.74%), (p = 0.001). Between the expression of p53 protein and Ki-67 protein in pterygium there was a significant positive correlation (p = 0.000). Conclusion. The prevalence of p53 positive samples of pterygium was 44%. The influence of sex and age on p53 protein expression in pterygium was not found. The increased proliferative acivity was present in the epithelium of pterygium. The expression of Ki-67 protein is associated with the expression of p53 protein in pterygium. The findings of our study support the thesis of pterygium as tissue growth disorder.

Expression and the prognostic relevance of p53, Bcl-2, Bax, and Ki-67 in uterine leiomyosarcoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15506-e15506
Author(s):  
Irina Rezo Gagua
Keyword(s):  
Disease Free Survival ◽  
Retrospective Chart Review ◽  
Female Reproductive Tract ◽  
Treatment Modalities ◽  
Uterine Leiomyosarcoma ◽  
Ki 67 ◽  
P53 Expression ◽  
Prognostic Relevance ◽  
Significant Difference ◽  
Disease Free

e15506 Background: Uterine leiomyosarcomas (LMS) are rare, aggressive gynecological malignancies of the female reproductive tract. They represent less than 2-5% of all uterine malignancies. Despite the advanced modern treatment modalities, according to our data 5 year overall and disease - free survival of patients with LMS is 48,5± 4,2% and 44.3 ± 4.3 %, respectively. One of the challenging directions in advancing the prognosis and optimization of treatment tactics in LMS is investigating the expression of molecular-biological markers in tumor tissue. So, the aim of our study was to evaluate the expression of p53, Bcl-2, Bax, and Ki-67 and their prognostic relevance. Methods: A retrospective chart review was done to 198 patients with LMS treated at the N.N. Blokhin Russian Cancer Research Center from 1971 to 2009. Immunohistochemical (IHC) staining for 20 patients was performed for p53, Bcl-2, Bax and Ki-67. Negative and positive IHC staining was scored for each marker. Survival was determined from the time of initial diagnosis to last follow-up. Results: Ten (50%) patients with LMS expressed p53. P53+ patients mostly had multiple metastases, compared to p53– patients with solitar metastases (60% against 20%) (g<0,05). Eleven (55%) patients expressed Bcl-2 and 4 (20%) expressed Bax. In Bcl-2 + patients distant metastases were observed in 45,5%, compared to Bcl-2 – patients were we observed metastatic disease in 77,8% (p=0,068). Expression of ki-67 was observed in 15 patients (75%). Conclusions: LMS patients with p53 expression had a poorer survival compared to LMS patients with negative expression (g53+ — 26,7±18,4% and g53– — 80,0±12,6%) (g<0,05). On opposite, the disease-free survivla is better in bcl-2+ patients, compared to patients, who don’t express bcl-2 (47,2±19,6% and 28,1±18,0%, respectevly (g>0,05). We didn’t observe statistical significant difference in survival depending on Bax expression. LMS patients with Ki-67 expression had a poorer survival compared to LMS patients with negative expression (34,9±13,1% and 60,0±20,7% , respectively) (g>0,05). Our study indicates that p53 expression may serve as a prognostic marker for LMS patients.

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

scholarly journals Integrating Systemic Therapies into the Multimodality Treatment of Resectable Colorectal Liver Metastases

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Omar Abdel-Rahman ◽  
Winson Y. Cheung
Keyword(s):  
Liver Metastases ◽  
Management Strategy ◽  
Multimodality Treatment ◽  
Treatment Modalities ◽  
Considerable Proportion ◽  
Optimal Management ◽  
Related Factors ◽  
Multiple Treatment ◽  
Current Review ◽  
Systemic Therapies

Colorectal carcinoma (CRC) is one of the most common cancers worldwide. A considerable proportion of CRC patients may present with metastatic disease either at upfront presentation (synchronous with the primary) or following diagnosis and treatment of the primary tumor (metachronous). Management of CRC liver metastases is a challenging endeavor which frequently necessitates proper assessment of patient- and disease-related factors. There is an opportunity within the management of CRC liver metastases to incorporate multiple treatment modalities (including surgery, other locoregional treatments, and systemic therapy). The current review aims to provide an updated overview on the optimal management strategy for CRC patients with liver metastases with a specific focus on the integration of systemic and/or locoregional treatments among patients with resectable or potentially resectable disease.

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferative Activity ◽  
P53 Protein ◽  
Myometrial Invasion ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Normal Endometrium ◽  
P53 Expression ◽  
Dna Polymerase Α ◽  
Endometrial Carcinomas

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.

Antitumor immune response is associated with favorable survival in GEP-NEN G3

2021 ◽  
Vol 28 (10) ◽  
pp. 683-693
Author(s):  
Vivian Rosery ◽  
Henning Reis ◽  
Konstantinos Savvatakis ◽  
Bernd Kowall ◽  
Martin Stuschke ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Spatial Interaction ◽  
Antitumor Immune Response ◽  
Cytotoxic T Cell ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed formalin-fixed paraffin-embedded samples from 37 patients with GEP-NEN G3 by immunohistochemistry and multiplex immunofluorescence to address the abundance and spatial interaction of relevant immune subsets. We focused on the expression of immune checkpoint molecules PD-1 and PD-L1, the cytotoxic T-cell marker CD8, and the tumor-associated macrophage marker CD206. Findings were correlated with overall survival (OS) from the date of a cancer diagnosis. Patients with PD-L1-positive tumors (CPS ≥ 1) and intense PD-1+CD8+ immune cell infiltration showed the most favorable median OS. Multiplex immunofluorescence staining of ten representative tissue samples illustrated intratumoral heterogeneity of PD-L1 expression. Dense PD-1+CD8+ immune cell infiltrates were observed in PD-L1-positive tumor regions but not in PD-L1-negative regions. Proximity analysis revealed a spatial interaction between PD-1+CD8+ cells and PD-L1-positive cells. Our data suggest a pre-existing antitumor immune response in the TME in a subgroup of GEP-NEN G3. This supports a targeted clinical exploration of immunotherapeutic approaches.

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