Squamous Cell Carcinoma Of Pharynx Research Articles

Investigation on the pharmacological profile for new synthesized bis heterocyclic analogs containing nitrogen atom as anti-cancer therapy target

Cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel heterocyclic compounds with pyridine, pyrimidine, and pyrazole rings 2–16 were synthesized and characterized using a variety of spectrum analyses. All synthesized compounds were evaluated for their anticancer effects on human lung carcinoma cell line (H460), human pharynx squamous cell carcinoma cell line (FaDu), and common human hepatocellular carcinoma cell line (Huh7), compounds 3 (6-ethoxy-pyridine), 8 (pyridinyl-pyrazol), 9 (pyridinyl-N, N-diacetylpyrazol), 11 (pyridinyl-N-(2,4-dinitrophenyl)pyrazole), 13 (pyridinyl-isoxazole) and 16 (pyridinyl-benzo[b][1,4]thiazepine) had the maximum anticancer activity against all examined cell lines. Based on these resultss, we are able to conclude that analoges 6-Ethoxy-pyridine 3, Pyridinyl-pyrazol 8, Pyridinyl-N-(2,4-dinitrophenyl)pyrazole 11 and Pyridinyl-benzo[b][1,4]thiazepine 16 are found to be secure and specific because their IC50 values on normal cell line are higher than their IC50 values on tested cancer cell lines.

Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma.

Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.

Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta-analysis.

The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow-up as reference. A bivariate generalized linear mixed model approach was used for the meta-analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86-0.96) and 0.97 (95% CI: 0.94-0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quality of life when omitting elective neck treatment based on SLNB.

A Case report on Plummer vinson Syndrome

PVS is a condition that can occur in people with long term exposure to iron deficiency anaemia. The exact cause of PVS is obscure.PVS classically presents as a triad of symptoms like –Iron deficiency anaemia/microcytic hypochromic anaemia, (post cricoids dysphagia, upper oesophageal webs. It generally occurs in premenopausal women. Even though the syndrome is very rare, now-a-days it’s recognition is very important because it identifies a group of patients at increased risk of squamous cell carcinoma of pharynx and oesophagus.The significance of Plummer Vinson syndrome is its association with cancers of head and neck[6] .We report a case of 65 years old male patient who has classical presentations of PVS. A male patient of age 65 years old was reported to general medicine department with complaints of- difficulty in swallowing sine 20 days; dysphagia to solids, not for liquids. Patient gave history of constipation on & off since 20 days associated with blood, scanty; history of passage of black coloured stools since 20 days; decreased appetite. Early diagnosing of PVS is important to prevent it’s complications. Treatment is primarily aimed at correcting the iron deficiency anaemia and oesophageal dilatation is done to provide symptomatic relief.

Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients.

Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients' characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of 'sphericity' and intratumoral characteristic of 'homogeneity' was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021.

Cyclodextrin nanosponge as a temoporfin nanocarrier: Balancing between accumulation and penetration in 3D tumor spheroids

As the intertissue delivery of hydrophobic temoporfin (mTHPC) remains inefficient, we propose the use of cyclodextrin-based nanosponges as a smart, advanced system for improved mTHPC delivery. Recently, we demonstrated that cyclodextrins (CDs) allow mTHPC to penetrate into tumor spheroids via a nanoshuttle mechanism. However, the CD complexes were very sensitive to the dilution, thus limiting their translation invivo. Hypercrosslinked CD monomers in a three-dimensional network (namely, CD nanosponges), however, may form both inclusion and non-inclusion complexes with drug molecules, providing controlled release and prolonged exposure to the drug. In the present work, we demonstrate that epichlorohydrin-crosslinked CD nanosponges based on β-CD (βCDp) and carboxymethyl-β-CD (CMβCDp) monomers efficiently encapsulated mTHPC. We calculated the apparent binding constants between mTHPC and CD polymers (K=(6.3–8.8) × 106M−1 and K=(1.2–1.7) × 106M−1 for βCDp and CMβCDp, respectively) using fluorescence titration curve fitting. The encapsulation of mTHPC in a CD polymer matrix had slower photosensitizer (PS) release compared to monomer CD units, providing deep penetration of mTHPC in 3D tumor spheroids in a concentration-dependent manner. However, the improvement of mTHPC penetration in 3D human pharynx squamous cell carcinoma (FaDu) spheroids using CD polymers was strongly accompanied by the inhibition of PS cellular uptake, demonstrating the delicate balance between the accumulation and the penetration of PS in FaDu spheroids. In summary, mTHPC-loaded CD nanosponges are a strong candidate for further invivo study in preclinical models, which could be considered as an advanced smart system for mTHPC delivery.

Chrysophanol Regulates Cell Death, Metastasis, and Reactive Oxygen Species Production in Oral Cancer Cell Lines.

Background Oral cancer belongs to the class of head and neck cancers and can be life threatening if not diagnosed and treated early. Activation of cell death via apoptosis or reactive oxygen species (ROS) accumulation and inhibition of cell cycle progression, migration, and epithelial-to-mesenchymal transition (EMT) may be a good strategy to arrest the development of oral cancer. In this study, we analyzed the possible action of chrysophanol isolated from the rhizomes of Rheum palmatum on the oral cancer cell lines FaDu (human pharynx squamous cell carcinoma) and SAS (human tongue squamous carcinoma) by investigating whether chrysophanol could influence cell death. Method Cell viability was measured by using the MTT assay. For the detection of apoptosis, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and subG1 population analysis were used. We also examined cell cycle progression and ROS levels by flow cytometry. Additionally, the expression of p53, p21, procaspase 3, cyclin D1, CDK4, cdc2, CDK2, E-cadherin, vimentin, and PCNA was evaluated by western blotting. Conclusion Chrysophanol has an anticancer effect on FaDu and SAS cell lines. There is an increase in subG1 accumulation, ROS production, and cell cycle G1 arrest after treatment with chrysophanol. On the other hand, chrysophanol inhibited cell migration/metastasis and EMT. We proposed that chrysophanol may be a good candidate compound on oral cancer treatment in the further.

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening.

Conventional 3D multicellular tumor spheroids of head and neck squamous cell carcinoma (HNSCC) consisting exclusively of cancer cells have some limitations. They are compact cell aggregates that do not interact with their extracellular milieu, thus suffering from both insufficient extracellular matrix (ECM) deposition and absence of different types of stromal cells. In order to better mimic in vivo HNSCC tumor microenvironment, we have constructed a 3D stroma-rich in vitro model of HNSCC, using cancer-associated MeWo skin fibroblasts and FaDu pharynx squamous cell carcinoma. The expression of stromal components in heterospheroids was confirmed by immunochemical staining. The generated co-culture FaDu/MeWo spheroids were applied to study penetration, distribution and antitumor efficacy of photoactive drugs such as Temoporfin and Chlorin e6 used in the photodynamic therapy flow cytometry and fluorescence microscopy techniques. We also investigated the distribution of photodiagnostic agent Indocyanine Green. We demonstrated that the presence of stroma influences the behavior of photoactive drugs in different ways: (i) No effect on Indocyanine Green distribution; (ii) lower accumulation of Chlorin e6; (iii) better penetration and PDT efficiency of Temoporfin. Overall, the developed stroma-rich spheroids enlarge the arsenal of in vitro pre-clinical models for high-throughput screening of anti-cancer drugs.

Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients

To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Carrot seed essential oil—Source of carotol and cytotoxicity study

Carrot seed essential oil is a common fragrance component in cosmetics and perfumes and a flavor ingredient in different categories of food products. It is also a major source of sesquiterpene alcohol carotol. In this work we aimed to compare carotol content in commercially available (Moroccan and French) and hydrodistilled (Polish) wild carrot seed essential oils (Daucus carota L. ssp. carota) and to evaluate cytotoxicity of these essential oils, as well as isolated carotol. The chemical composition of studied essential oils was analysed by gas chromatography- mass spectrometry. Cytotoxicity tests were performed on green monkey kidney (VERO) and human pharynx squamous cell carcinoma (FaDu) cell lines. Carotol and other terpenoids were isolated using high performance counter current chromatography technique in the reversed phase mode, with a mixtures of n-hexane/acetonitrile/tetr-butyl methyl ether (1:1:0.1 and 2:1:0.1v/v). Carotol was the main constituent in three carrot seed essential oils of different origin amounting 19–33% of the sum of compounds. α-Pinene, sabinene, myrcene, limonene, geranyl acetate, bisabolene, cayophyllene oxide and daucol were identified as other main compounds. Separation of 280mg of carrot seed essential oil yielded carotol (20mg) and other terpenoids: α-pinene, sabinene, limonene, geranyl acetate, caryophyllene oxide, and daucol with the purity in the range of 80–99%. The applied method enabled isolation of all main constituents of essential oil in the single run. The comparison of cytotoxicity of tested essential oils on VERO and FaDu cell lines indicated that Moroccan and French essential oils have similar cytotoxicity (35.3–46.1μg/mL), while Polish essential oil showed lower cytotoxic effect (70.9–96.3μg/mL). Carotol being the main constituent of all tested essential oils showed moderate cytotoxicity on both tested cell lines without any selectivity.

Sarcomatoid squamous cell carcinoma of pharynx: A case report with immunohistochemical study

Primary sarcomatoid squamous cell carcinoma (S-SCC) of pharynx is a very rare tumor. A 77-year-old woman presented with sore throat. Laryngoscope revealed an infiltrating tumor of lower pharynx. The tumor was ulcerated and measured 3 cm × 4 cm × 3 cm. The tumor was invasive and involved the surrounding tissues. Biopsies showed sarcomatous malignant spindle cell proliferation as well as invasive well-differentiated squamous cell carcinoma (SCC). The former occupied 80% and the latter 20%. Gradual transitions between malignant spindle cells and SCC were frequently seen. The histological diagnosis was S-SCC. Immunohistochemically (the results are shown in Table 1), the tumor cells were positive for vimentin, cytokeratin (CK) AE1/3, CK CAM5.2, CK WSS, CK KL-1, CK MNF-15, CK5, CK6, CK7, CK8, CK 18, CK19, p53 and Ki67 (labeling index = 65%), but negative for CK34BE12, CK20, EMA, S100 protein, NSE, NCAM, synaptophysin, chromogranin, desmin, -smooth muscle actin, smooth muscle actin (HHF-35), h-caldemon, CD31, factor VIII-related antigen, CD34, HMB45, KIT, PDGFRA, CA19-9, CEA, bcl-2, CD3, CD20, CD45, CD138, myoglobin, HPV, and EBER. The author’s diagnosis was S-SCC. The patient received chemotherapy and radiation, and is now in complete remission 3 years after the diagnosis.

Increase of Phosphatase and Tensin Homolog by Silymarin to Inhibit Human Pharynx Squamous Cancer

Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.

GW24-e0518 Recurrent syncope as initial symptom in pharynx squamous cell carcinoma

ObjectivesSyncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat.MethodsIn such cases, surgery,...

P137. MUC1: probable correlation with c-Met in oral and pharynx squamous cell carcinoma

P137. MUC1: probable correlation with c-Met in oral and pharynx squamous cell carcinoma

The expression of EGFR, HER2 and EpCam in Head and Neck squamous cell carcinomas

PURPOSE: Head and Neck squamous cell carcinomas show an increasing incidence and make up to 5% of all malignancies. In this work three cell surface proteins are investigated, which could be possible targets in currently arising tailored cancer treatment: Epithelial cell adhesion molecule (EpCam), the epidermal growth factor receptor (EGFR, c-erbB-1 or HER1) and HER2/neu (c-erbB-2). MATERIALS AND METHODS: In this study, specimens from 114 histologically verified squamous cell carcinoma of pharynx and oral cavity were analysed. The surface proteins were tested with pharmacodiagnostic kits. RESULTS: With 44.7% (51/114) EGFR was found to be overexpressed most frequently in this cohort. A usable distribution for EpCam and nearly lacking of HER2 was shown in 22.8% (26/114) and 3.5 % (4/114), respectively. CONCLUSION: These data show that EGFR and EpCam might have a relevant role for the biology of this disease. Its relevance for a therapeutic application cannot yet be concluded.

Changes from 1992 to 2002 in the pretreatment delay for patients with squamous cell carcinoma of larynx or pharynx: A Danish nationwide survey from DAHANCA

In Denmark, a general impression of prolonged pretreatment delay for patients with head and neck cancer led to a nationwide study of time spans from symptom debut over first health care contact to start of treatment. Charts of consecutive new patients with squamous cell carcinoma of the pharynx and larynx, seen at the five Danish oncology centers in January–April 1992 and 2002, respectively, were reviewed. Of the 288 patients identified, definitive treatment was radiotherapy in 264 cases, surgery in one case. Twenty-three patients had neither surgery nor radiotherapy. Total time from first health care contact to start of definitive treatment was significantly longer in 2002 than in 1992 (median 70 versus 50 days, p < 0.001). There was no significantly difference in time used for diagnosis. Time for treatment preparation and planning was 46 days in 2002 versus 31 days in 1992 (p < 0.001). Significantly more diagnostic procedures (CT, MR, US, PET) were done in 2002. In conclusion, this nationwide study showed that waiting time before start of radiotherapy was significantly longer in 2002 compared to 1992. An increasing number of imaging procedures including CT-based dose planning was observed. The prolongation was mainly related to shortage of radiotherapy capacity. The three weeks extra pretreatment delay could theoretically lead to a 10% lower tumor control probability in 2002 compared to 1992.

Genetic Analysis of Primary and Metastatic Larynx and Pharynx Squamous Cell Carcinoma

Genetic Analysis of Primary and Metastatic Larynx and Pharynx Squamous Cell Carcinoma

Chromosomal Changes in relation to Clinical Outcome in Larynx and Pharynx Squamous Cell Carcinoma

Invasive head and neck squamous carcinomas are among the cytogenetically most complex tumors. Perhaps for this reason, there is little consensus on the prognostic value of specific chromosomal aberrations. Here we present Results of CGH analysis of 56 clinically well-characterized set of head and neck cancers, consisting of larynx and pharynx only. The aim was to find possible associations with clinical outcome. The major chromosome arms showing gains were (in decreasing order): 3q, 7q, 8q, 5p, 11q13, 17q and 18p, and losses occurred at 3p, 11qter, 4p, 18q, and 5q. The segments most frequently amplified were 3q26-qter, 11q13, 11q22, 3q12–13, 18p11.3, 18q11.2 and 8q24.3. Tumors with stages III and IV, and lymph node positive tumors had a worse clinical outcome. Surprisingly, no specific chromosomal abnormality correlated with disease-free survival. The only aberration that correlated to one of the clinico-pathological parameters was amplification 11q13, that occurred solely in lymph node positive, stage IV tumors. However 11q13 amplification did not correlate with disease-free survival. These Results seem to indicate that genetic alterations at the level of chromosomes have limited prognostic value in patients with invasive larynx and pharynx squamous cell carcinomas.

咽頭原発類基底細胞癌の２例

咽頭原発類基底細胞癌の２例

Reactivation of telomerase in squamous epithelial carcinomas in the area of the head and neck

Head and neck cancer development involves the accumulation of multiple cellular alterations over a long period of time. Selection and expansion of altered cell clones can lead to the evolution of a malignant phenotype. The theory of carcinogenesis suggests that unlimited cell proliferation is required for development of malignant disease and cancer must attain immortality for progression to malignant states. One step in the immortalization process may be the reactivation of telomerase. This enzyme complex can prevent the continuous shortening of telomeres which is observed at each cell cycle. Telomerase activity was detected in 68% of squamous cell carcinomas of pharynx and larynx and 58% of histologically tumor-free resection margins. Recurrences occurred with a higher rate in cases with telomerase positive primary tumor. The importance of telomerase activity in histologically negative resection margins needs further investigations. Telomerase activity was found in 90% of corresponding lymph nodes without any correlation to metastasis in the lymph node. The reactivation of telomerase seems to be an important step in carcinogenesis of head and neck cancers. Further studies are necessary in order to understand the role of the enzyme as a possible marker for tumor progression and clinical outcome.