Role of Cytokines in Combinatorial Immunotherapeutics of Non-Small Cell Lung Cancer Through Systems Perspective

Misra, Pragya; Singh, Shailza

doi:10.2139/ssrn.3245682

Cited by 3 publications

(4 citation statements)

References 116 publications

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“…At present, therapeutic options for LC include radiotherapy and chemotherapy. Despite the rapid development of modern technology and treatments, the mortality rate of patients with LC remains high, and a tendency for relapse has been observed 3,4 …”

Section: Introductionmentioning

confidence: 99%

“…Despite the rapid development of modern technology and treatments, the mortality rate of patients with LC remains high, and a tendency for relapse has been observed. 3,4 The ubiquitin-proteasome system is the master pathway of protein degradation in the cytoplasm and nucleus of mammals. The highly regulated ubiquitin-proteasome pathway affects various cellular processes, substrates, and imperfections in the system, leading to the pathogenesis of cancer in humans.…”

Section: Introductionmentioning

confidence: 99%

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ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

et al. 2022

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Background Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. Methods LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP. Results ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar. Conclusion Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

et al. 2022

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“…There were an estimated more than 20,000 morbidity and 14,000 mortality due to lung cancer in 2019 [1] . Non-small cell lung cancer (NSCLC) is the most common histopathological subtype of LC, accounting for about 85% of all LC, of which squamous cell carcinoma and adenocarcinoma are the most common subtypes [2,3] . Although improvements have been made in diagnostic and therapeutic techniques, many cases were still diagnosed at an advanced stage with poor diagnosis [4] .…”

Section: Introductionmentioning

confidence: 99%

A Nomogram with Lymph Node Status Predicts Survival and the Benefit of Postoperative Radiotherapy in IIIA-N2 Non-small Cell Lung Cancer Patients after Surgery

Chen

Dong

et al. 2020

Preprint

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Objective: This study aimed at establishing a novel nomogram predicting overall survival and investigating the survival benefit of postoperative radiotherapy in IIIA-N2 Non-small cell lung cancer (NSCLC) patients after surgery.Methods: Data of IIIA-N2 NSCLC patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER). Patients were excluded if the information regarding follow-up time and clinicopathological features were incomplete. Through Univariate and multivariate analyses, independent prognostic factors were identified and integrated into the construction of nomogram. The survival benefit of PORT was investigated in model-defined low-risk, intermediate-risk, and high-risk subgroups, respectively.Results: In total, 4389 patients were finally included for analysis. Patients’ age, sex, T stage, differentiation grade, examined lymph nodes number (ELN), metastatic lymph nodes number (MLN), and metastatic lymph nodes ratio (LNR) were identified as independent prognostic factors and were integrated into the construction of nomogram. The C-index and calibration curves indicated that the predictive performance of the nomogram was satisfactory. Patients were then categorized into three prognostic groups with the increasing risk of all-cause of death. Only patients in high-risk group could benefit from PORT.Conclusion: In this large-cohort retrospective study, A survival-predicting nomogram and risk stratification model were established to estimate prognosis in IIIA-N2 NSCLC patients. PORT was recommended for those patients in high-risk group. This study may provide additional integration, introspection, and improvement for therapeutic decision-making.

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“…There are an estimated more than 20,000 morbidity and 14,000 mortality due to lung cancer in 2019 [1] . Non-small cell lung cancer (NSCLC) is the most common histopathological subtype of LC, accounting for about 85% of all LC, of which squamous cell carcinoma and adenocarcinoma are the most common subtypes [2,3] . Although improvements have been made in diagnostic and therapeutic techniques, many cases were still diagnosed at an advanced stage with poor diagnosis [4] .…”

Section: Introductionmentioning

confidence: 99%

A nomogram with lymph node status predicts survival and the benefit of postoperative  adjuvant therapy in IIIA-N2 Non-small cell lung cancer patients after surgery

Chen¹,

Dong²,

Li³

et al. 2020

Preprint

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Objective: This study aimed at establishing a novel nomogram predicting overall survival and investigating the survival benefit of various postoperative adjuvant treatments (POAT) in IIIA-N2 Non-small cell lung cancer (NSCLC) patients after surgery.Methods: Data of IIIA-N2 NSCLC patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER). Patients were excluded if the information regarding follow-up time and clinicopathological features were incomplete. Through Univariate and multivariate analyses, independent prognostic factors were identified and integrated into the construction of nomogram. The survival benefit of POAT was evaluated in model-defined low-risk, intermediate-risk, and high-risk subgroups, respectively.Results: In total, 4389 patients were finally included for analysis. Patients’ age, sex, T stage, differentiation grade, examined lymph nodes number (ELN), metastatic lymph nodes number (MLN), and metastatic lymph nodes ratio (LNR) were identified as independent prognostic factors and were integrated into the construction of nomogram. The C-index and calibration curves indicated that the predictive performance of the nomogram was satisfactory. Patients were then categorized into three prognostic groups with the increasing risk of all-cause of death. The prognosis of patients receiving POAT (POCT or PORT plus POCT) and patients receiving surgery alone was comparable in low-risk group, while POCT could significantly prolong survival for IIIA-N2 NSCLC patients after surgery in moderate-risk and high-risk groups. Only patients in high-risk group could benefit from the combination of postoperative radiotherapy (PORT) and postoperative chemotherapy (POCT).Conclusion: In this large-cohort retrospective study, A survival-predicting nomogram and risk stratification model were established to estimate prognosis in IIIA-N2 NSCLC patients. Surgery alone was recommended as the first choice of treatment to patients in low-risk group. POCT was recommended for patients in moderate-risk group, and the combination of PORT and POCT was recommended for patients in high-risk group. This study may provide additional integration, introspection, and improvement for therapeutic decision-making.

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Role of Cytokines in Combinatorial Immunotherapeutics of Non-Small Cell Lung Cancer Through Systems Perspective

Cited by 3 publications

References 116 publications

ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

A Nomogram with Lymph Node Status Predicts Survival and the Benefit of Postoperative Radiotherapy in IIIA-N2 Non-small Cell Lung Cancer Patients after Surgery

A nomogram with lymph node status predicts survival and the benefit of postoperative  adjuvant therapy in IIIA-N2 Non-small cell lung cancer patients after surgery

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Role of Cytokines in Combinatorial Immunotherapeutics of Non-Small Cell Lung Cancer Through Systems Perspective

Cited by 3 publications

References 116 publications

ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells

A Nomogram with Lymph Node Status Predicts Survival and the Benefit of Postoperative Radiotherapy in IIIA-N2 Non-small Cell Lung Cancer Patients after Surgery

A nomogram with lymph node status predicts survival and the benefit of postoperative&nbsp;&nbsp;adjuvant therapy in&nbsp;IIIA-N2&nbsp;Non-small cell lung cancer&nbsp;patients after surgery

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A nomogram with lymph node status predicts survival and the benefit of postoperative adjuvant therapy in IIIA-N2 Non-small cell lung cancer patients after surgery