Carcinoma Patients Research Articles

Objective to identify and verify the regulatory mechanism of DTNBP1 as a prognostic marker for hepatocellular carcinoma

Although the overall survival of hepatocellular carcinoma (HCC) patients has been significantly improved, prognostic clinical evaluation remains a substantial problem owing to the heterogeneity and complexity of tumor. A reliable and accurate predictive biomarker may assist physicians in better monitoring of patient treatment outcomes and follow the overall survival of patients. Accumulating evidence has revealed that DTNBP1 plays functional roles in cancer prognosis. Therefore, the expression and function of DTNBP1in HCC was systematically investigated in our study. The expression and prognostic value of DTNBP1 were investigated using the data from Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) cohorts and clinical samples. A series of cellular function assays were performed to elucidate the effect of DTNBP1 on cellular proliferation, apoptosis and metastasis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and Protein–protein interaction (PPI) network construction were performed to screen the genes with highest interaction scores with DTNBP1. Finally, the underlying mechanism was also analyzed using Gene Set Enrichment Analysis (GSEA) and confirmed using RT-qPCR and western blotting. DTNBP1 was upregulated in many types of cancers, especially in HCC. The DTNBP1 expression levels is associated with clinicopathologic variables and patient survival status. The differential expression of DTNBP1 could be used to determine the risk stratification of patients with HCC. DTNBP1 deficiency inhibited cell proliferation and metastasis, but promoted cell apoptosis. Mechanistically, DTNBP1 regulated the cell cycle progression through affecting the expression of cell cycle-related genes such as CDC25A, CCNE1, CDK2, CDC20, CDC25B, CCNB1, and CDK1. DTNBP1, which regulates the cell cycle progression, may be used as a prognostic marker for HCC.

AVL9 promotes colorectal carcinoma cell migration via regulating EGFR expression

BackgroundDespite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear.AimTo investigate the biological role and mechanism of AVL9 in colorectal carcinoma.ResultsAVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration.ConclusionThese findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, suggesting a potential biomarker and treatment target for CRC.

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis

PurposeTo evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors.MethodsA total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed.ResultsThe median follow-up time for the whole group was 31.5 months (range 5–138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/μl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS.ConclusionTaxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

RNA N6-methyladenosine reader IGF2BP2 promotes lymphatic metastasis and epithelial-mesenchymal transition of head and neck squamous carcinoma cells via stabilizing slug mRNA in an m6A-dependent manner

BackgroundLymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined.MethodsThe expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, luciferase reporter and mRNA stability assays were performed to explore the epigenetic mechanism of IGF2BP2 in HNSCC.ResultsWe investigated 20 m6A-related regulators in HNSCC and discovered that only the overexpression of IGF2BP2 was associated with a poor OS probability and an independent prognostic factor for HNSCC patients. Additionally, we demonstrated that IGF2BP2 was overexpressed in HNSCC tissues, and significantly correlated to lymphatic metastasis and poor prognosis. Functional studies have shown that IGF2BP2 promotes both HNSCC cell migration as well as invasion via the epithelial-mesenchymal transition (EMT) process in vitro, and IGF2BP2 knockdown significantly inhibited lymphatic metastasis and lymphangiogenesis in vivo. Mechanistic investigations revealed that Slug, a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC. Furthermore, we demonstrated that IGF2BP2 recognizes and binds the m6A site in the coding sequence (CDS) region of Slug and promotes its mRNA stability.ConclusionsCollectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.

Total thyroidectomy versus hemithyroidectomy with intraoperative radiofrequency ablation for unilateral thyroid cancer with contralateral nodules: A propensity score matching study

BackgroundFor unilateral papillary thyroid carcinoma (PTC) patients with contralateral benign nodules, optimal treatment decisions are made according to patient preference and the disease’s pathological features. This study was performed to evaluate the efficacy and complications of hemithyroidectomy with intraoperative radiofrequency ablation (RFA) compared with total thyroidectomy.MethodsPatients with unilateral PTC and cytologically benign contralateral nodules were enrolled from 2014 to 2018. Total thyroidectomy or hemithyroidectomy with intraoperative RFA of the contralateral nodule was offered to patients who had anxiety regarding their disease. The operation-related parameters, transient or permanent nerve injury, hypocalcemia and disease recurrence, were recorded and compared between the two groups.ResultsAfter propensity score matching, 191 patients who underwent total thyroidectomy and 224 contralateral nodules in 191 patients underwent hemithyroidectomy with intraoperative RFA (HTRFA) were included. The volume reduction ratios of the contralateral nodules were 67.7% at 12 months and 95.8% at 24 months. The total thyroidectomy group reported significantly higher hypocalcemia than HTRFA within one year (7.8% vs. 2.6%, p = 0.022). Supplemental levothyroxine was not required in 28.3% (54/191) of the patients one year after HTRFA. With a median follow-up of 4.1 years, three recurrences (1.6%) were observed in the HTRFA, and no recurrence occurred in the total thyroidectomy group (p = 0.246).ConclusionsHemithyroidectomy for unilateral PTC and intraoperative RFA for contralateral nodules were acceptable and effective treatment approaches and did not increase the risk of complications.Graphical

Detection of Marker Associated with CTC in Colorectal Cancer in Mononuclear Cells of Patients with Benign Inflammatory Intestinal Diseases.

Simple SummaryColorectal carcinoma (CRC) is one of the most frequent cancers in western countries, and non-invasive methods for early detection are still needed. Circulating tumor cells (CTC) in blood of CRC patients have been proven as prognostic and predictive biomarker; however, the suitability of CTC-associated markers for early CRC detection and discrimination from benign diseases has not been analyzed. Thus, this study investigated whether CTC-associated markers can also be detected in the blood of patients with benign inflammatory intestinal disease (IID) or whether they are specific for malignancy. The detection rate of CK20 and DEFA5 clearly differed in diseased patients and healthy controls, while LAD1 and PLS3 was found in all samples but with clear qualitative differences in gene expression. No association between inflammation severity and CTC marker expression was found in IID patients. Finally, PLS3 was identified to be a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls.Colorectal carcinoma (CRC) belongs to the most common tumor entities in western countries. Circulating tumor cells (CTC) in blood of CRC patients are a powerful prognostic and predictive biomarker. However, whether CTC-associated markers can also be used for early CRC detection and discrimination from benign diseases is not known. This study investigated the presence of CTC-associated markers CK20, PLS3, LAD1, and DEFA5 in blood of patients with benign inflammatory intestinal disease (IID) and their correlation with malignancy. The detection rate of CK20 and DEFA5 significantly differed between diseased patients and healthy controls. LAD1 and PLS3 were detected in all samples with clear differences in gene expression. DEFA5 expression was higher in CRC and IID patients compared to healthy donors, while CK20 and PLS3 were lower in CRC compared to IID patients or healthy controls. Overall, all CTC-associated markers were detectable in blood of IID patients, but not correlating with inflammation severity. Finally, PLS3 emerged as a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls, however its suitability for early CRC detection needs to be further validated.

The relationship between TESTIN expression and the prognosis of colorectal cancer

BackgroundColorectal carcinoma (CRC) represents a most grave healthy burden worldwide. TESTIN has been confirmed as a predictive biomarker for several cancers. In the present study, we sought to assess the expression level and prognostic values of TESTIN in CRC. MethodsThe levels of TESTIN mRNA and protein were detected in 132 paired CRC tissues and noncancerous ones via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) assays, respectively. Chi-square test was adopted to analyze the association of TESTIN expression with clinicopathological profiles of CRC patients. To explore prognostic value of TESTIN, Kaplan-Meier curve and Cox regression analyses were employed. ResultsTESTIN expression was down-regulated among CRC tissues in comparison to bordering cancer-free samples at both protein and mRNA levels (P < 0.001). Decreased TESTIN expression was closely related to poor tumor differentiation (P = 0.001) and advanced TNM stages (P = 0.001). CRC cases with low expression of TESTIN were more likely to undergo dismal overall survivals (log-rank P = 0.003). Multivariate Cox analysis unveiled that down-regulated expression of TESTIN was independently correlated with poor prognosis (HR=2.422, 95% CI=1.294–4.535, P = 0.006). ConclusionThe down-regulation of TESTIN may predict dismal prognosis for CRC patients.

Clinical Values and Markers of Radiation-Induced Liver Disease for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Stereotactic Body Radiotherapy.

BackgroundInformation about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients.MethodsIn our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up.ResultsMedian overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p < 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p < 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p < 0.05).ConclusionsThe development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients.

Cyberknife Radiosurgery for the Treatment of Head and Neck Cancer: A Systematic Review.

Cyberknife radiosurgery is a frameless stereotactic robotic radiosurgery which has shown to deliver better treatment outcomes in the treatment of advanced head and neck (H&N) carcinomas, especially in previously irradiated and recurrent cases. The aim of the study was to perform a systematic review of the available data on the outcomes of Cyberknife radiosurgery for treatment of head and neck cancer and to evaluate its collective outcomes. This systematic review was registered with the university with the registration no. FRP/2019/63 and was approved by the Institutional Review Board (RC/IRB/2019/132). Literature search was performed in the following: PubMed, Science direct, SciELO, MyScienceWork, Microsoft Academ EMBASE, Directory of Open Access Journals, and Cochrane databases with the keywords “Cyberknife,” “oral cancer,” “oropharyngeal cancer,” and “head and neck cancer” and data was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The records identified were 147 manuscripts. Excluded articles included 5 duplicate articles, 33 abstracts, 101 full text articles due to being off-topic, case reports, review, non-English, 1 survey, and 2 other articles containing data extracted from a main study which was already included. A total of 5 articles were evaluated for qualitative synthesis. The mean dose of Cyberknife radiosurgery delivered for previously irradiated recurrent H&N carcinoma patients was 34.57 Gy, with a mean sample size of 5 studied during the period of 2000 to 2016. The available evidence from the systematic review indicates that Cyberknife can be an efficacious treatment option for recurrent previously irradiated H&N carcinoma, especially for nonresectable tumors. There is paucity of homogenous data and studies in this arena; hence, meta-analysis could not be performed. Further standardized studies are essential, especially where the treatment of H&N carcinoma is considered.

Pan-cancer analysis of N4-acetylcytidine adaptor THUMPD1 as a predictor for prognosis and immunotherapy.

Background: THUMPD1 is a specific RNA adaptor that assists acetylation of mRNA and production of N4-acetylcytidine (ac4C). However, it remains unclear whether THUMPD1 plays a part in tumorigenesis and therapeutic efficacy. Here, we analyzed the expression profiles and prognostic value of THUMPD1 in pan-cancer and gained insights into the correlation between THUMPD1 expression level and immunotherapy efficacy.Methods: Gene expression pattern and its correlation with prognosis, immune cell infiltration in pan-cancer were obtained from Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) databases, with Kaplan–Meier method and Spearman correlation analysis used. Western blotting and immunofluorescence on clinical samples were performed to validate our database-derived results. Correlation between THUMPD1 expression level and immunotherapy responses was also explored, based on clinical cohorts receiving programmed cell death protein 1 ligand (PD-L1) antibody therapy. Finally, gene set enrichment analysis (GSEA) was performed to show the possible tumorigenic mechanism.Results: THUMPD1 was highly expressed in most cancer types, and this elevated expression indicated poor or improved prognosis for different cancers. In kidney renal clear cell carcinoma (KIRC) and rectum adenocarcinoma (READ), patients with higher THUMPD1 expression exhibited a better prognosis, while liver hepatocellular carcinoma (LIHC) patients had worse prognosis. Besides, THUMPD1 was significantly associated with immune cell infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints and neoantigen in many cancer types. Further, more clinical advantages and therapeutic responses were observed in patients with high THUMPD1 expression.Conclusions: THUMPD1 may serve as a novel predictor to evaluate cancer prognosis and immune therapy efficacy in diverse cancer types.

Methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in head and neck squamous cell carcinoma (HNSCC) and correlated with patient’s poor prognosis

Abstract Objective To investigate methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, biological function, and correlation with head and neck squamous cell carcinoma (HNSCC) patient’s prognosis. Methods The relative expression levels of MTHFD2 gene mRNA in tumor tissues of HNSCC and adjacent normal tissues were analyzed in the Cancer Genome Atlas and oncomine database. MTHFD2 protein relative expression in tumor tissue of HNSCC patients was analyzed in human proteome database. Protein–protein interaction (PPI) network of MTHFD2 and correlated genes were constructed in STRING database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of MTHFD2 and relevant proteins involved in the PPI network was enriched. The Tumor Immune Estimation Resource database was used to analyze the relationship between MTHFD2 expression and immune infiltration. Overall survival (OS) and progression-free survival (PFS) for MTHFD2 high and low expression groups were investigated in the Kaplan–Meier Plotter database. Results In HNSCC, MTHFD2 mRNA relative expression level in tumor tissue was significantly higher than the corresponding normal tissue with statistical difference (p &lt; 0.05). In the PPI network, 21 protein coding genes were involved in the network with 124 edges, which indicated that the enrichment was significant (p &lt; 0.05). MTHFD2 and PPI network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process. In KEGG pathway, MTHFD2 and PPI network involved genes were mainly enriched in one-carbon pool by folate, metabolic pathways, glyoxylate, and dicarboxylate metabolism, and carbon metabolism. The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p &lt; 0.05), neutrophil (r = 0.158, p &lt; 0.05), dendritic cell (r = 0.1825, p &lt; 0.05), and CD4+ T lymph cell (r = 0.1825, p &lt; 0.05). HNSCC patients with high expression MTHFD2 had low OS compared to low expression cases (hazard ratio = 1.53, 95% CI: 1.16–2.02, p &lt; 0.05). Conclusion MTHFD2 is overexpressed in HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provides a possible direction for the research and development of related targeted drugs.

Metabolic tumour volume on 18F-FDG PET/CT predicts extended pathological T stages in patients with renal cell carcinoma at staging

We evaluated the predictive value of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/CT (PET/CT) for extended pathological T (pT) stages (≥ pT3a) in Renal cell carcinoma (RCC) patients at staging. Thirty-eight RCC patients who underwent 18F-FDG PET/CT at staging, followed by radical nephrectomy between September 2016 and September 2018, were included in this prospective study. Patients were classified into two groups (limited pT stage: stage T1/2, n = 17; extended pT stage: T3/4, n = 21). Univariate and multivariate logistic regression analyses were performed to identify clinicopathological and metabolic variables to predict extended pT stages. 18F-FDG metabolic parameters were compared in relation to International Society of Urological Pathology (ISUP) grade and lymphovascular invasion (LVI). In univariate analysis, maximum standardised uptake value, metabolic tumour volume (MTV), and ISUP grade were significant. In multivariate analysis, MTV was the only significant factor of extended pT stages. With a cut-off MTV of 21.2, an area under the curve was 0.944, which was higher than 0.824 for clinical T stages (p = 0.037). In addition, high MTV, but not tumour size, was significantly correlated with aggressive pathologic features (ISUP grade and LVI). High glycolytic tumour volume on 18F-FDG PET/CT in RCC patients at staging is predictive of extended pT stages which could aid decision-making regarding the best type of surgery.

The first two cases of posterior reversible encephalopathy syndrome (PRES) secondary to conventional transcatheter arterial chemoembolization of hepatocellular carcinoma

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a very rare complication secondary to transcatheter arterial chemoembolization (TACE). Only two patients with liver metastasis have been reported. We report for the first time two cases of hepatocellular carcinoma (HCC) patients occurred PRES secondary toTACE.Case presentationThe two patients with HCC developed headache, epilepsy, expressive aphasia, visual impairment and loss of consciousness, 11 and 3 h after conventional TACE (c-TACE) surgery. One patient experienced raised blood pressure during and after TACE, accompanied by a significant elevated creatinine. The magnetic resonance imaging (MRI) of the two patients showed multiple abnormal signals in the brain, mainly located in the white matter region. Combined with the clinical symptoms and MRI findings, PRES was diagnosed. Their symptoms and MRI changes improved significantly in the next two weeks.ConclusionThe PRES in this report is chemoembolization-associated syndrome, which might be related to the use of chemotherapy agents during TACE. And if neurological symptoms occur after TACE, patients should be closely monitored to exclude PRES.

Abstract P120: Novel in vitro targeted combination therapies for anaplastic thyroid cancer

Abstract Purpose: To identify effective drug combination strategies targeting multiple oncogenic pathways in anaplastic thyroid cancer. Background: Treatments with BRAF and MEK inhibitors induce impressive tumor size reduction in most BRAF-mutated anaplastic thyroid carcinoma (ATC) patients. However, these drugs are ultimately ineffective due to resistance development, probably because ATC cells express multiple oncogenic pathways that can be used to bypass the treatments. Therefore, the identification of novel therapeutic strategies is still urgently needed. We had previously identified additional pathways/targets (TWIST1, MMP9, BCL2, TGFβR, and the stress kinase MAPK14/p38α) by reverse-phase protein arrays (RPPA) and microarray analysis. In this study, we report the in vitro effects of inhibitors specific for the identified targets used alone or in combination with BRAF inhibitors. Methods: We established mouse ATC cell lines (MCH2.2-Luc and PPA6-Luc) to graft into immunocompetent syngeneic animals. As a first step, these lines were treated in vitro for 72 hours with increasing concentrations of nine different inhibitors for the above targets, and the MTS colorimetric assay determined viability/IC50. We also tested the combinatorial effects of these compounds with BRAF inhibitors (vemurafenib or dabrafenib) and compared them to single agents’ effects. Also, we investigated the colony-forming ability and apoptotic response of these cell lines. Results: IC50 concentrations for nine different compounds were calculated. Both cell lines showed similar IC50 values, except that PPA6-Luc was more resistant to the BRAF inhibitor dabrafenib than MCH2.2-Luc. The MMP-9 inhibitor and the PARP inhibitor olaparib did not significantly affect the growth of these lines. Among three different MAPK14/p38α inhibitors tested, ralimetinib was the most effective (IC50 @ 15 mM). Importantly, venetoclax (BCL2 inhibitor) and harmine (TWIST1 inhibitor) effectively inhibited cell growth with an IC50 of 8 µM and 25 mM, respectively. Treatments using 0.1mM dabrafenib or 1mM vemurafenib in combination with 4 other drugs (5 mM each below the IC50) resulted in significant synergy only with ralimetinib (38% growth decrease) and harmine (37% growth decrease) compared to treatments with single agents. Colony-forming assays confirmed the growth suppression. Conclusions: Inhibiting specific targets previously identified by RPPA and microarray analysis demonstrated, for the first time, in differential ATC cell growth suppression. Notably, only a combination of specific inhibitors (dabrafenib combined with the TWIST1 or the MAPK14/p38α inhibitors) resulted in synergy, suggesting that these targeted combinations will be more effective in our preclinical ATC mouse model than the other drugs. By treating these combinations in a mouse model may contribute, in the future, to the development of clinical and therapeutic strategies for aggressive thyroid cancer. Citation Format: Muthusamy Kunnimalaiyaan, Parag Parekh, Jalyn Golden, Ying Anderson, Stephen Lai, Maria Cabanillas, Marc Zafereo, Ramona Dadu, Marie-Claude Hofmann. Novel in vitro targeted combination therapies for anaplastic thyroid cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P120.

Postoperative recurrence with right cervical lymph node metastasis in hepatocellular carcinoma: a case report

BackgroundHepatocellular carcinoma (HCC) patients with metastases to the cervical lymph nodes are extremely rare, and its clinical course is characterized by rapidly progressive disease. Hence, there have been no reports of metastatic cervical lymph node recurrence indicated after a long postoperative surveillance period.Case presentationThe patient was a 63-year-old male who underwent right hepatectomy for HCC of the right upper lobe. Three years after resection, metastatic lymph node recurrence was detected in the subdiaphragm, superior mediastinum, and right cervical lymph nodes. The patient underwent excisional biopsy of the cervical lymph node, followed by molecular-targeted therapy and radiation therapy. Lenvatinib reduced the size of all metastatic lymph nodes and the patient survived for a relatively long period of 43 months after the recurrence was detected.ConclusionsAfter resection of HCC in the right upper lobe, there is the possibility of metastatic lymph node recurrence in unusual sites, including the cervical region, and lenvatinib may be effective in those recurrences.

Ferrocene‐derivative Electrochemical Probe for the Selective Detection of Carcinoma‐associated STn Antigen

AbstractFerrocene‐derivatives have a well‐defined electrochemical behaviour, which can be changed upon binding to other molecules (including nonelectroactive species), as the conjugate presents a slower diffusion to the electrode surface. Therefore, the binding event can be easily detected by monitoring the decrease in the current intensity of the ferrocene‐derivative oxidation peak. An electrochemical probe composed of ferrocenecarboxylic acid conjugated with Sambucus nigra agglutinin was prepared and used to selectively detect the STn antigen, a pan‐carcinoma glycobiomarker. The probe showed high selectivity towards the STn antigen present in glycoproteins and demonstrated effectiveness in the analysis of serum samples from carcinoma patients.

Immune-related Liver Injury is a Poor Prognostic Factor in Patients with Nonsmall Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in nonsmall cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days postinjection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the nonliver-irAEs group (128 and 722 days; P = 0.010 and P = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.

Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress

ABSTRACT Introduction Unfortunately, some hepatocellular carcinoma (HCC) patients do not qualify for curative-intent treatments such as surgical resection or transplantation. Hence, locoregional treatments such as transarterial chemoembolization (TACE) remain instrumental in the treatment of HCC. Systemic therapy has improved over the past decade with the introduction of combination atezolizumab and bevacizumab as the new standard of care for advanced disease. These new therapies are currently under investigation in combination with TACE. Area covered Combination therapies with TACE including systemic therapies, locoregional therapies, and immunotherapies are reviewed. Expert opinion There has been limited progress in the management of advanced and intermediate HCC. Recent advances in the management of advanced disease with systemic therapy could be beneficial in combination with TACE for the treatment of intermediate stage disease. Immune based therapies are potentially beneficial in combination with TACE because TACE may produce increased antigen release and immune recognition.

Cerebral Structural Abnormalities and Their Associations With Peripheral Cytokine Levels in a Group of Untreated Patients With Nasopharyngeal Carcinoma.

The current study is to characterize the alterations of peripheral cytokines and anatomical brain changes, and their relationships in untreated nasopharyngeal carcinoma (NPC) patients with depressive symptoms. Twenty-nine newly diagnosed NPC patients without any treatment and 46 matched healthy comparisons were recruited, scanned with high-resolution T1 images and assessed psychologically using Hamilton Rating Scale for Depression (HAMD). Serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) were measured by quantitative chemiluminescence assay. Inter-group comparisons of anatomical brain measures were performed, and regions with significant inter-group differences were correlated to HAMD scores and cytokines in NPC patients. A subgroup analysis especially within NPC patients with depression was conducted to precisely characterize the associations among serum cytokines, brain changes and depressive symptoms. Relative to healthy subjects, NPC patients showed significantly decreased cortical thickness in the left parahippocampal gyrus, increased surface area in the right superior parietal lobule and precentral gyrus, and increased gray matter volume in the right postcentral gyrus, bilateral caudate nucleus and right thalamus, as well as significantly elevated IL-1β, IL-2 and IL-10. The elevated IL-2 and IL-10 were negatively correlated with surface area in right superior parietal lobule, whilst IL-1β level was positively correlated to HAMD scores. In patients with depression, specific brain changes and evaluated IL-1β were identified, and the IL-1β interacted with right precentral gyrus to significantly affect the depressive symptoms. Our findings provide novel evidence indicating potential effects of inflammation on brain structure and behavior in NPC patients.

Clinicopathologic characteristics of patients with endometrial cancer and their treatment outcome in BPKMCH

Background: There are few studies on endometrial carcinoma in Nepal so present study aims to evaluate the clinicopathologic characteristics of endometrial cancer patients along with their treatment outcome.&#x0D; Material and Methods: This is a descriptive study conducted from January 2011 to December 2020 and all patients of endometrial carcinoma who had undergone primary surgery at B.P. Koirala Memorial Cancer Hospital were included. Socio-demographic characteristics, clinical presentations, histologic type, treatment modalities and outcomes were obtained and analyzed.&#x0D; Results: The mean age was found to be 58 8.32 years. Most were postmenopausal accounting for 86%. Medical co-morbidities were associated in 40% of patients. Most common presentation was postmenopausal bleeding seen in 68% of patients. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was done in 48% of patients. The main histologic type was endometrioid carcinoma observed in 96% of patients. Low grade carcinoma was found in 78% of patients out of which grade 1 accounting for 50% and rest grade 2 while high grade carcinoma was found 22% of patients. 64% of patients required adjuvant therapy. Recurrence was seen in 16% of patients.&#x0D; Conclusions: Endometrial carcinoma is common in post menopausal age group. Endometrioid variety is the commonest histologic type. Clinicopathologic characters of endometrial carcinoma affect the prognosis of the patient.