scholarly journals PD-1/PD-L1-negative tracheal mucoepidermoid carcinoma: A case report and systematic review of the literature

2022 ◽  
pp. 260
Author(s):  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cell Types ◽  
Intermediate Cell ◽  
Sleeve Lobectomy ◽  
Cell Lung Carcinoma ◽  
Segmental Bronchus ◽  
Intermediate Cells ◽  
Chinese Male

Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery. Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.

scholarly journals PD-1/PD-L1-negative tracheal mucoepidermoid carcinoma: A case report and systematic review of the literature

2021 ◽  
Author(s):  
Ying Ying Liu ◽  
Jian Guo ◽  
Ji Chen ◽  
Hai Xia Li ◽  
Zeng Tao Wang ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cell Types ◽  
Intermediate Cell ◽  
Sleeve Lobectomy ◽  
Cell Lung Carcinoma ◽  
Segmental Bronchus ◽  
Intermediate Cells ◽  
Chinese Male

Abstract Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery.Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.

scholarly journals The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices

2020 ◽  
Vol 14 ◽  
Author(s):  
Federica Di Cintio ◽  
Michele Dal Bo ◽  
Lorena Baboci ◽  
Elena De Mattia ◽  
Maurizio Polano ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Alkylating Agents ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Types ◽  
Molecular Signature ◽  
Central Nervous System Tumor ◽  
Cell Lung Carcinoma

Glioblastoma (GBM) is the most frequent and aggressive primary central nervous system tumor. Surgery followed by radiotherapy and chemotherapy with alkylating agents constitutes standard first-line treatment of GBM. Complete resection of the GBM tumors is generally not possible given its high invasive features. Although this combination therapy can prolong survival, the prognosis is still poor due to several factors including chemoresistance. In recent years, a comprehensive characterization of the GBM-associated molecular signature has been performed. This has allowed the possibility to introduce a more personalized therapeutic approach for GBM, in which novel targeted therapies, including those employing tyrosine kinase inhibitors (TKIs), could be employed. The GBM tumor microenvironment (TME) exerts a key role in GBM tumor progression, in particular by providing an immunosuppressive state with low numbers of tumor-infiltrating lymphocytes (TILs) and other immune effector cell types that contributes to tumor proliferation and growth. The use of immune checkpoint inhibitors (ICIs) has been successfully introduced in numerous advanced cancers as well as promising results have been shown for the use of these antibodies in untreated brain metastases from melanoma and from non-small cell lung carcinoma (NSCLC). Consequently, the use of PD-1/PD-L1 inhibitors has also been proposed in several clinical trials for the treatment of GBM. In the present review, we will outline the main GBM molecular and TME aspects providing also the grounds for novel targeted therapies and immunotherapies using ICIs for GBM.

scholarly journals Trichostatin A downregulates bromodomain and extra-terminal proteins to suppress osimertinib resistant non-small cell lung carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuting Meng ◽  
Xixi Qian ◽  
Li Zhao ◽  
Nan Li ◽  
Shengjie Wu ◽  
...  
Keyword(s):  
Trichostatin A ◽  
Small Cell Lung Carcinoma ◽  
Cell Types ◽  
Inhibitory Effects ◽  
Cell Lung Carcinoma ◽  
Growth Inhibitory ◽  
Terminal Proteins ◽  
P Cells

Abstract Background The third-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients with non-small cell lung carcinoma (NSCLC) who carry active EGFR mutations, as well as those who have developed acquired resistance to the first-generation of EGFR-TKIs due to the T790M mutation. However, most patients develop drug resistance after 8–10 months of treatment. Currently, the mechanism has not been well clarified, and new therapeutic strategies are urgently needed. Methods Osimertinib resistant cell lines were established by culturing sensitive cells in chronically increasing doses of osimertinib. The anticancer effect of reagents was examined both in vitro and in vivo using the sulforhodamine B assay and a xenograft mouse model. The molecular signals were detected by western blotting. The combination effect was analyzed using CompuSyn software. Results We found that bromodomain and extra-terminal proteins (BETs) were upregulated in osimertinib resistant (H1975-OR) cells compared with those in the paired parental cells (H1975-P), and that knockdown of BETs significantly inhibited the growth of H1975-OR cells. The BET inhibitor JQ1 also exhibited stronger growth-inhibitory effects on H1975-OR cells and a greater expression of BETs and the downstream effector c-Myc than were observed in H1975-P cells. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) showed stronger growth suppression in H1975-OR cells than in H1975-P cells, but vorinostat, another HDAC inhibitor, showed equal inhibitory efficacy in both cell types. Consistently, downregulation of BET and c-Myc expression was greater with TSA than with vorinostat. TSA restrained the growth of H1975-OR and H1975-P xenograft tumors. The combination of TSA and JQ1 showed synergistic growth-inhibitory effects in parallel with decreased BET and c-Myc expression in both H1975-OR and H1975-P cells and in xenograft nude mouse models. BETs were not upregulated in osimertinib resistant HCC827 cells compared with parental cells, while TSA and vorinostat exhibited equal inhibitory effects on both cell types. Conclusion Upregulation of BETs contributed to the osimertinib resistance of H1975 cells. TSA downregulated BET expression and enhanced the growth inhibitory effect of JQ1 both in vitro and in vivo. Our findings provided new strategies for the treatment of osimertinib resistance.

scholarly journals Immunocheckpoint Inhibitor- (Nivolumab-) Associated Hypereosinophilia in Non-Small-Cell Lung Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Navdeep Singh ◽  
Sandeep Singh Lubana ◽  
George Constantinou ◽  
Andrea N. Leaf
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Lung Carcinoma ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Eosinophil Counts

Immunocheckpoint inhibitor (ICI) therapy has provided significant clinical improvements in the treatment of several malignancies. The purpose of this report is to increase awareness of hypereosinophilia associated with checkpoint inhibitors, a topic that has been rarely reported. Hypereosinophilia may need to be addressed especially if eosinophil counts increase to levels where hypereosinophilic visceral complications can occur. We are presenting a case of a 57-year-old male with hypereosinophilia that was seen in the setting of progression of metastatic non-small-cell lung cancer during and after nivolumab treatment.

Bone metastases treated with immune checkpoint inhibitors: A single center experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14105-e14105 ◽  
Author(s):  
Punita Grover ◽  
Vidhya Karivedu ◽  
Zheng Zhu ◽  
Roman Jandarov ◽  
Trisha Michel Wise-Draper
Keyword(s):  
Bone Metastases ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Performance Status ◽  
Univariate Analysis ◽  
Additional Treatment ◽  
Treatment Modalities ◽  
Combination Immunotherapy ◽  
Cell Lung Carcinoma ◽  
Combination Methods

e14105 Background: We conducted a retrospective study to analyze the overall survival (OS) and progression free survival (PFS) among patients with bone metastases (BMs) from Non Small Cell Lung Carcinoma (NSCLC), Melanoma, Head and Neck Squamous Cell Carcinoma (HNSCC) and others (including genitourinary carcinoma) treated with immunotherapy (Nivolumab, Pembrolizumab, Ipilimumab or a combination). Methods: We retrospectively evaluated patients with BMs treated at our institute from 2012-2017 who received either immunotherapy alone or in combination with other therapies for BMs including: medical therapy (zoledronic acid or denosumab), radiation or surgery. Univariate analysis was utilized to analyze OS and PFS. Results: A total of 58 patients were identified, median age at diagnosis of BMs was 61 years (range 29 – 94). 39 patients were male (67.2%) and 47(81%) patients had good performance status (KPS 70-100) at the time of immunotherapy initiation. The median time to diagnosis of BMs was 11.4 months. 20 patients had a single BM, 16 had 2-4 BMs and 22 had ≥5 BMs. Axial-only BMs were seen in 27 patients, appendicular-only in 8 and both in 23 patients. 40 patients were symptomatic and 28 patients had skeletal events (pathological fractures, spinal cord compression or hypercalcemia). 51 patients had other metastatic sites at the time of initiation of immunotherapy. 25 patients received nivolumab, 20 patients received pembrolizumab and 4 patients received combination immunotherapy. 41 patients received additional treatments for BMs. The median OS from the start of immunotherapy was 5.15 months and median PFS was 3 months. On univariate analysis male sex (p = 0.03) and combination immunotherapy (p = 0.06) were associated with better OS. Patients who received additional treatments for BMs (p = 0.04) and combination immunotherapy (p = 0.02) had better PFS. Conclusions: Combination immunotherapy and use of additional treatment modalities for BMs is associated with better survival. Further analysis is required to validate these results. [Table: see text]

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