Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer.

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

Great auricular nerve schwannoma in neck region: a case report with the risk of medical disputes.

BACKGROUND: Great auricular nerve schwannoma is extremely rare. Herein, we reported the first case of schwannoma arising from great auricular nerve trunk. CASE PRESENTATION: A 29 year-old female complained of a slowly-growing superfacial neck mass for 6 months. MRI revealed a high possibility of schwannoma. Although the patient underwent successfully surgical removal of the tumor, ipsilateral numbness of both auricle and peripheral skin developed due to traction of the nerve. Immunohistochemistry staining confirmed the diagnosis of schwannoma. And the patient has been followed regularly. CONCLUSION: For superficial cervical tumors, the cervical plexus cutaneous nerve should be considered if MRI and other imaging findings suggest neurogenic tumors.

Cervical metastasis of gingival carcinoma misdiagnosed as branchiogenic carcinoma, a rare entity - report of a case and review of literature.

BACKGROUND: A cervical cystic mass is associated with a number of pathologies that present with similar symptoms. These conditions are difficult to differentiate using fine-needle aspiration (FNA), ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). Another dilemma in the differential diagnosis of cervical cystic masses is due to the controversies associated with the existence of branchiogenic carcinoma (BC). BC is an extremely rare disease that must be differentiated from other conditions presenting with cervical cystic masses, especially cystic metastasis from occult primary lesions. CASE PRESENTATION: We present a case report of a right cervical cystic metastasis from a significantly small squamous cell carcinoma primary gingival lesion misdiagnosed as BC by histopathology. A 62-year-old female presented with a painless progressively enlarging cervical mass at the anterior edge of the sternocleidomastoid muscle in the right submandibular region. Preoperative MRI and US revealed a well-defined cystic round mass. Postoperative histological examination indicated BC. Positron emission tomography/computed tomography (PET/CT) revealed high 18F-FDG (18F 2-fluoro-2-deoxy-D-glucose) uptake in surgical regions with a SUV (standard uptake value) max 4.0 and ipsilateral nasopharynx with a SUVmax 4.4, without any distant metastasis. Pathologic results revealed nasopharyngeal lymphadenosis. Considering the low incidence of BC and the limitation of diagnosis in one institution, the patient was referred to another hospital. Physical examination detected a significantly small neoplasm (~3 mm diameter) in the right lower gingiva. Histopathological examination of the neoplasm revealed a well-differentiated squamous cell carcinoma. Surgery, including a partial mandibulectomy and modified neck dissection (neck level I-V and submental lymph nodes) were undertaken. Postoperative histopathological results revealed a well-differentiated squamous cell carcinoma of right lower gingiva and two metastatic lymph nodes in the 18 lymph nodes of level II. A month later, recurrence occurred in the right cervical level II. The patient was placed on postoperative concurrent chemo-radiotherapy and supportive care. The patient suffered from cachexia and survived for only six months after surgery. CONCLUSIONS: In cases of cervical cystic masses that appear after the age of 40, clinicians should bear in mind that occult primary lesions should be excluded and examination of the gingiva should be undertaken. PET/CT has a limited role in identifying small occult primary lesions and a comprehensive physical examination must be carefully performed.

Leveraging single-cell RNA-seq for uncovering naïve B cells associated with better prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a typical highly heterogeneous solid tumor with high morbidity and mortality worldwide, especially in China; however, the immune microenvironment of HCC has not been clarified so far. Here, we employed single-cell RNA sequencing (scRNA-seq) on diethylnitrosamine (DEN)-induced mouse HCC model to dissect the immune cell dynamics during tumorigenesis. Our findings reveal distinct immune profiles in both precancerous and cancerous lesions, indicating early tumor-associated immunological alterations. Notably, specific T and B cell subpopulations are preferentially enriched in the HCC tumor microenvironment (TME). Furthermore, we identified a subpopulation of naïve B cells with high CD83 expression, correlating with improved prognosis in human HCC. These signature genes were validated in The Cancer Genome Atlas HCC RNA-seq dataset. Moreover, cell interaction analysis revealed that subpopulations of B cells in both mouse and human samples are activated and may potentially contribute to oncogenic processes. In summary, our study provides insights into the dynamic immune microenvironment and cellular networks in HCC pathogenesis, with a specific emphasis on naïve B cells. These findings emphasize the significance of targeting TME in HCC patients to prevent HCC pathological progression, which may give a new perspective on the therapeutics for HCC.

[Isolated metastasis of the ascending ramus of the mandible of thyroid follicular carcinoma: a case report].

The mandibular metastatic spread of carcinoma from the thyroid gland is exceedingly rare. Follicular thyroid carcinoma is the second most common type of thyroid carcinoma，accounting for approximately 10% to 15% of all thyroid cancers. The prognosis of FTC is relatively satisfactory. Due to its rich blood transport, it is easy to metastasize hematological, with the main sites of metastasis are bone and lung. However，mandibular metastasis of thyroid follicular carcinoma is rare. We report a case of thyroid follicular carcinoma that metastasized to the ascending ramus of the mandible 21 years after surgery.The operation was successfully completed, and there was no recurrence during postoperative follow-up. Due to the absence of obvious clinical symptoms in the patient, the diagnosis and treatment were challenging. We have provided detailed radiographic and pathological images to facilitate understanding and discussion of the disease.

Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.

Head and neck squamous cell carcinoma (HNSCC) is the major pathological type of head and neck cancer (HNC). The disease ranks sixth among the most common malignancies worldwide, with an increasing incidence rate yearly. Despite the development of therapy, the prognosis of HNSCC remains unsatisfactory, which may be attributed to the resistance to traditional radio-chemotherapy, relapse, and metastasis. To improve the diagnosis and treatment, the targeted therapy for HNSCC may be successful as that for some other tumors. Nanocarriers are the most effective system to deliver the anti-cancerous agent at the site of interest using passive or active targeting approaches. The system enhances the drug concentration in HCN target cells, increases retention, and reduces toxicity to normal cells. Among the different techniques in nanotechnology, quantum dots (QDs) possess multiple fluorescent colors emissions under single-source excitation and size-tunable light emission. Dendrimers are the most attractive nanocarriers, which possess the desired properties of drug retention, release, unaffecting by the immune system, blood circulation time enhancing, and cells or organs specific targeting properties. In this review, we have discussed the up-to-date knowledge of the Cancer Stem Cells of Head and Neck Squamous Cell Carcinoma. Although a lot of data is available, still much more efforts remain to be made to improve the treatment of HNSCC.

Anion-tuned nickel chalcogenides electrocatalysts for efficient 2e- ORR towards H2O2 production in acidic media.

Electrocatalytic 2e- oxygen reduction reaction (2e- ORR) is a promising approach to producing H2O2 at ambient temperature and pressure especially in acidic media, which, however, is hindered by the high cost of precious metal-based electrocatalysts. Hence, the development of efficient earth-abundant electrocatalysts and reaction mechanism exploration for H2O2 production by 2e- ORR in acidic solution are critically important but remain challenging at present. In this work, NiSe2 has been developed as a novel and high-performance 2e- ORR electrocatalyst in acidic media, moreover, using nickel chalcogenides as the models, the influence of different anion species (Se22-, S22-, and O2-) on 2e- ORR electrocatalytic performance of the catalysts has been investigated. The synthesized NiSe2 exhibits outstanding 2e- ORR performance of high selectivity (90%) and long-term durability (12 h). The maximum H2O2 concentration of NiSe2 reaches 988 ppm, which is the highest among all the reported transition metal chalcogenides. This work demonstrates a novel point of view in anion tuning for designing high-efficiency transition-metal-based electrocatalysts for 2e- ORR. Electronic Supplementary Material: Supplementary material (additional experimental procedures, characterizations, and computational details) is available in the online version of this article at 10.1007/s12274-022-5160-2.

Misuse of traditional Chinese medicine may be a risk factor to tumorigenesis and progression of head and neck carcinoma in China: a hypothesis based on a case series.

PURPOSE: In China, many patients with head and neck carcinoma prefer traditional Chinese medicine (TCM) as their first therapy. However, several components of TCM have been identified as being toxic. We hypothesize that misuse and over-application of TCM can contribute to tumorigenesis and progression of head and neck carcinoma. RESULTS: Three head and neck cancer patients were the subjects of this report. The first patient with squamous cell carcinoma got TCM without surgery, chemotherapy or radiotherapy which resulted in disease progression. The patient was then subjected to palliative surgery followed by concurrent chemoradiotherapy (CCRT). The second patient with mucoepidermoid carcinoma of the parotic gland received TMC as first-line therapy with rapid disease progression. This was followed by complete parotidectomy and postoperative CCRT. The third patient with laryngeal squamous cell carcinoma took oral TVM for 8 years to treat psoriasis. Due to recent complaints he was radically operated and received postoperative CCRT. CONCLUSION: Due to its unclear components, potential toxicities, misuse, and over-application, TCM might contribute to tumorigenesis and progression of head neck carcinoma. We seek effective approaches to ensure the safe use of TCM.

Synergistic combination of PEGylated selenium nanoparticles and X-ray-induced radiotherapy for enhanced anticancer effect in human lung carcinoma.

In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNP + X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.

Advances in recurrence and malignant transformation of sinonasal inverted papillomas.

Sinonasal inverted papilloma (SIP) is a benign tumor of the nasal cavity and sinus. SIP is characterized by aggressive malignant transformation and a high rate of recurrence. Inadequate removal of the tumor during surgery is one of the most significant contributors to SIP recurrence. A growing body of evidence suggests that molecular alteration in SIP, including human papilloma virus infections, single nucleotide polymorphisms of key genes, deregulation of signaling pathways and immunological changes, may lead to SIP occurrence and malignant transformation. However, the extent to which these molecular mechanisms contribute to SIP pathology and transformation remains unclear due to limited research. Further studies are warranted to elucidate the primary dependent factors that contribute to SIP etiology. The present article reviewed risk factors of progression and recurrence of SIP, including outdoor and industrial occupational exposure, smoking, septal deviation, SIP location, recurrent cases, stage of SIP-associated squamous cell carcinoma and choice of surgical method.

Targeting cyclic hypoxia to prevent malignant progression and therapeutic resistance of cancers.

Emerging evidence shows that cyclic hypoxia exists in most solid cancers. It is believed that under cyclic hypoxic conditions cancer cells exhibit more malignant biological behaviors than under chronic hypoxic conditions. In this review, we provide a collection of evidence showing the molecular mechanisms by which cyclic hypoxia induces aggressiveness, malignant progression, and therapeutic resistance in cancers. Moreover, we propose that cyclic hypoxia is responsible for the regulation of cancer stem cells, which possess typical biological characteristics of therapeutic resistance. Based on the present findings, some key factors regulated by cyclic hypoxia may serve as potential targets for the prevention of malignant progression and the treatment of solid cancers. Much research is necessary to gain further insights into the biological aspects of cyclic hypoxia in the development and progression of cancers.

Hypoxia promotes radioresistance of CD133-positive Hep-2 human laryngeal squamous carcinoma cells in vitro.

Hypoxia promotes the radioresistance of laryngeal carcinomas and CD133 is one of the markers expressed by tumor-initiating, human laryngeal carcinoma cells. In order to investigate whether CD133-positive Hep-2 cells exhibit a radioresistant phenotype and to determine whether hypoxia promotes this phenotype, we performed a series of experiments. Hep-2 cells, and Hep-2 cells stably expressing hypoxia-inducible factor (HIF)-targeted small interfering RNA (siRNA) were cultured under hypoxic and normoxic conditions and were treated with varying doses of γ-rays (0, 5, 10, 15 and 20 Gy). MTT and cell cycle assays were subsequently performed. Using fluorescence-activated cell sorting (FACS), CD133-positive Hep-2 cells and CD133-positive HIF-siRNA Hep-2 cells were isolated. These cells were grown as spheres under hypoxic and normoxic conditions for MTT and soft agar colony formation assays. The expression levels of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), survivin, p53 and ataxia-telangiectasia mutated (ATM) were also assayed using flow cytometry. The data showed that the growth of Hep-2 cells exposed to hypoxic conditions and treated with 10 Gy radiation (group A) was less compared to that of groups B-D (P<0.05). In addition, more cells in group A were arrested in the G1 phase of the cell cycle compared to groups B-D (P<0.05). The percentage of CD133+ cells detected after radiation increased and was the highest for group A (P<0.05). In sphere formation assays, significantly more CD133+ cells grew in spheres than CD133- cells (P<0.001). Moreover, sphere formation was the highest for CD133+ Hep-2 cells grown under hypoxic conditions and exposed to irradiation (group E) (P<0.05). Lastly, expression of DNA-PKcs and survivin for group E was the highest (P<0.05), while ATM and p53 levels remained largely unchanged (P>0.05). In conclusion, CD133-positive Hep-2 cells exhibited a radioresistant phenotype that was enhanced with hypoxia. Furthermore, an increase in DNA-PK activity was associated with this enhancement.

[Expression of hypoxia inducible factor-1α and correlated target genes in human laryngeal carcinoma].

OBJECTIVE: To detect the expression of hypoxia inducible factor 1 alpha (HIF-1α), glucose transporter protein-1 (GLUT-1) and vascular endothelial growth factor (VEGF) in human laryngeal carcinoma tissue, and to study the relationship between hypoxia and HIF-1α, GLUT-1, VEGF in human laryngeal carcinoma Hep-2 cells and to explore the effect of HIF-1α, GLUT-1 and VEGF as endogenous hypoxic markers on laryngeal carcinoma. METHODS: The expression levels of HIF-1α, GLUT-1 and VEGF were detected in 35 cases of laryngeal carcinoma by SP immunohistochemical methods and in Hep-2 cells by SP immunocytochemical methods. The relationship between HIF-1α and GLUT-1, VEGF protein expression was analyzed. RESULTS: Of the 35 cases, 16 cases expressed HIF-1α, 16 cases expressed GLUT-1, 19 cases expressed VEGF. The expression of HIF-1α and VEGF were closely correlated with pathologic grading and lymphnode metastasis. GLUT-1 was correlated with lymphnode metastasis. The expression levels of HIF-1α, GLUT-1 and VEGF in Hep-2 cells under hypoxic condition were higher than those under normoxic condition. CONCLUSION: HIF-1α may promote the expression of GLUT-1 and VEGF in laryngeal carcinoma, furthermore promote tumor angiogenesis, invasion, and metastasis of the laryngeal carcinoma.

Regulation of glucose transporter protein-1 and vascular endothelial growth factor by hypoxia inducible factor 1α under hypoxic conditions in Hep-2 human cells.

The present study evaluated the regulation of glucose transporter protein-1 (Glut-1) and vascular endothelial growth factor (VEGF) by hypoxia inducible factor 1α (HIF-1α) under hypoxic conditions in Hep-2 human cells to explore the feasibility of these three genes as tumor markers. Hep-2 cells were cultured under hypoxic and normoxic conditions for 6, 12, 24, 36 and 48 h. The proliferation of Hep-2 cells was evaluated using an MTT assay. The protein and mRNA expression levels of HIF-1α, Glut-1 and VEGF were detected using the S-P immunocytochemical method, western blotting and reverse transcription polymerase chain reaction (RT-PCR). The results revealed that the expression levels of HIF-1α, Glut-1 and VEGF protein in Hep-2 cells were significantly elevated under hypoxic conditions compared with those under normoxic conditions over 36 h. Under hypoxic conditions, mRNA levels of HIF-1α were stable, while mRNA levels of Glut-1 and VEGF changed over time. In conclusion, Glut-1 and VEGF were upregulated by HIF-1α under hypoxic conditions in a time-dependent manner in Hep-2 cells and their co-expression serves as a tumor marker.

Cancer stem cells may be mostly maintained by fluctuating hypoxia.

We wonder if most cancer stem cells (CSCs) survive and are maintained in the region of fluctuating hypoxia, which protects them against differentiation. Fluctuating hypoxia, as an important and neglected factor, has been confirmed to induce malignant progression, confer to therapeutic resistance and exist extensively. The subsequent consequence is similar with the behavior of CSCs. Therefore, we cite some examples for our bases and hypothesize CSCs may be mostly maintained by fluctuating hypoxia.

[Cancer stem cells promotes resistance of laryngeal squamous cancer to irradiation mediated by hypoxia].

OBJECTIVE: To study whether cancer stem cells promotes resistance of laryngeal squamous cancer to irradiation mediated by hypoxia. METHOD: Hep-2 cells were respectively cultured in hypoxia and normoxia environment, and the express of HIF-la was detected by western blot. Then they were radiated with different doses of gamma-rays. After that we detected growth inhibition ratio with MTT assay, cell circle and ratio of CD133+ cells with Flow cytometry at different times. RESULT: MTT assay showed that inhibition ratio of the hypoxia group was lower than that of the normoxia group after different doses of gamma-rays at each time point, and the difference was significant 24 h after 10 Gy irradiation (P < 0.05). The results of Flow cytometry demonstrated that cells of the two groups were arrested at G1 phase, and cells ratio in G1 phase of the hypoxia group was higher than that of he normoxia group after 10 Gy irradiation. The ratio of CD133-positive cells was higher in the hypoxia group than in the normoxia group after radiation, and difference was significant 24 h after 10 Gy irradiation (P < 0.05). In each group, the ratio of CD133-positive cells became higher after radiation than that before radiation (P < 0. 05). CONCLUSION: We can conclude that cancer stem cells play an important role in radioresistance mediated by hypoxia.

[Cancer stem cells play an important role in resistance of laryngeal squamous cancer to irradiation mediated by hypoxia].

OBJECTIVE: To study whether laryngeal cancer stem cells in hypoxia have the characteristic of resistance to irradiation and underlying mechanism. METHODS: CD133(+) cells were separated from Hep-2 cells with flow cytometry (FCM) and the purity was 92.8%. The separated CD133(+) cells were cultured in serum-free medium in hypoxia in normoxia environment respectively, and hypoxia-inducible factor 1 alpha (HIF-1α) expression was detected by FCM. The cells were exposed respectively to X-rays emitted by linear accelerator with a dose of 0, 5, 10, 15 or 20 Gy for 24 hours, with additional time points of 12, 36, and 48 hours for the cells exposed to 10 Gy. Then the growth inhibition ratios of cells in hypoxia and normoxia groups were detected with MTT assay at different time points. Soft agar colony formation assay was used to detect colony formation ratios of cells in hypoxia and normoxia groups. DNA dependent protein kinase catalytic subunit (DNA-PKcs), ataxia telangiectasia mutate (ATM), Survivin and P53 were detected by FCM. RESULTS: Growth inhibition ratio of CD133(+) cells in hypoxia group was lower than that in normoxia group (P < 0.05). Colony formation ratio of CD133(+) cells was higher than that of CD133(-) cells (P < 0.01) and the ratio of CD133(+) cells in hypoxia group was higher than that in normoxia group (P < 0.05). The ratio of hypoxia group was not affected by irradiation, while the ratio of normoxia group decreased significantly after irradiation (P < 0.05). The expressions of DNA-PKcs, ATM, Survivin and P53 in CD133(+) cells were higher than those in CD133(-) cells respectively (P < 0.01). In CD133(+) cells with radiation, the expressions of DNA-PKcs and Survivin of hypoxia group were higher those of normoxia group (P < 0.05), but no difference in the expression of ATM or P53 between the two groups. CONCLUSIONS: Laryngeal cancer stem cells play an important role in radioresistance mediated by hypoxia.