Paclitaxel-loaded polymeric nanoparticles based on α-tocopheryl succinate for the treatment of head and neck squamous cell carcinoma: in vivo murine model.

The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects. A polymeric nanocarrier system was developed for the delivery of PTX to improve HNSCC treatment. This study aimed to evaluate the antitumor efficacy of PTX-loaded polymeric nanoparticles based on α-TOS (PTX-NPs) administered by direct intratumoral injection into a Hypopharynx carcinoma squamous cells (FaDu) tumor xenograft mouse model. The nanocarrier system based on block copolymers of polyethylene glycol (PEG) and a methacrylic derivative of α-TOS was synthesized and PTX was loaded into the delivery system. Tumor volume was measured to evaluate the antitumor effect of the PTX-NPs. The relative mechanisms of apoptosis, cell proliferation, growth, angiogenesis, and oxidative and nitrosative stress were detected by Western blotting, fluorescent probes, and immunohistochemical analysis. The antitumor activity results showed that compared to free PTX, PTX-NPs exhibited much higher antitumor efficacy and apoptosis-inducing in a FaDu mouse xenograft model and demonstrated an improved safety profile. Ki-67, EGFR, and angiogenesis markers (Factor VIII, CD31, and CD34) expression were significantly lower in the PTX-NPs group compared with other groups (p < .05). Also, PTX-NPs induced oxidative and nitrosative stress in tumor tissue. Direct administration of PTX-loaded polymeric nanoparticles based on α-Tocopheryl Succinate at the tumor sites, proved to be promising for HNSCC therapy.

Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma.

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.

α-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of Head and Neck Squamous Cell Carcinoma.

The aim of this work is to study, in an in vitro head and neck squamous cell carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the newly synthetized α-TOS-loaded NPs in proliferating endothelial cells and hypopharynx carcinoma squamous cells and measured markers of angiogenesis, apoptosis and reactive oxygen species (ROS). α-TOS-loaded NPs suppressed angiogenesis by inducing accumulation of ROS and inducing apoptosis of proliferating endothelial cells. These NPs also decrease the number and quality of capillary-like tubes in an in vitro three-dimensional (3D) experiment, decrease the production of the pro-angiogenic vascular endothelial growth factor and down-regulate the expression of its receptor. The anti-migratory efficacy of α-TOS is corroborated in hypopharynx carcinoma cells by decreasing the secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting cell migration. These results confirm that α-TOS-based NPs not only present anticancer properties, but also antiangiogenic properties, therefore making them promising candidates for multi-active combinatorial anticancer therapy.

Occult esophageal squamous cell carcinoma with metastases to the spine and central nervous system.

Esophageal malignancy encompasses a group of diseases that are mostly represented by the squamous cell carcinoma and the adenocarcinoma. Quite frequently, these neoplasms present aggressive behavior; therefore, the diagnosis is often made when the condition is in advanced stages. Dysphagia is the typical clinical complaint, although it is present only when most of the lumen is obstructed. Therefore, quite often, the metastatic disease is first diagnosed, which contributes to the patient's poor survival expectancy. The authors report the case of a 58-year-old man who looked for medical care complaining of a long-term history of scapular pain. The diagnostic work-up disclosed a cervical spine lytic lesion surrounded by a tumoral mass shown by computed tomography. The cervical tumor was sampled by fine needle aspiration, revealing an undifferentiated carcinoma. The outcome was unfavorable and the patient died. The autopsy findings revealed metastatic disease to the spine and central nervous system, and the primary tumor was found to be an esophageal squamous cell carcinoma, which had progressed without typical dysphagia.

Evolução dos doentes com citologia oncótica alterada e colposcopia anal normal / Outcome of patients with anal oncotic cytology alterations and normal anal colposcopy

A citologia anal vem sendo usada para rastreamento do carcinoma anal e suas lesões precursoras nas populações de risco. Quando o raspado do canal anal mostra alterações citológicas está indicada o exame com colposcópio e ácido acético para identificar e realizar biópsia para confirmar o achado. Poucos estudos mostram o seguimento dos doentes tratados de condilomas acuminados perianais. Temos usado os métodos em associação e encontrado lesões subclínicas em metade dos doentes, cujo exame proctológico não revelava doença HPV induzida. Essas lesões são tratadas com tópicos. Entretanto, algumas citologias estavam alteradas e a colposcopia anal não revelou doença HPV induzida. O objetivo deste estudo foi observar o comportamento dessas lesões no seguimento semestral, durante 12 meses, e avaliar se a periodicidade da reavaliação foi suficiente para evitar o aparecimento das lesões de alto grau ou superior. Encontramos 58 (21 por cento) entre 273 doentes nessas condições. As reavaliações de 22 deles após um ano mostraram que as colposcopias permaneceram normais em 17 (74 por cento), sendo que em cinco (22 por cento) a citologia voltou aos padrões normais e 12 (52 por cento) persistiram com alterações. Os outros seis (26 por cento) desenvolveram lesões clínicas ou subclínicas provocadas pelo HPV. As contagens de linfócitos T CD4 dos doentes HIV-positivos foram inferiores nos doentes cujas lesões progrediram. Os resultados permitiram concluir que as alterações podem progredir ou regredir neste grupo distinto de doentes, sendo relacionada à imunidade, e que o intervalo de seis meses é suficiente para cada reavaliação.

Anal cytology has been used for screening the anal carcinoma and its precursors in risk populations. When anal canal smear shows cytological alterations, examination with colposcope and acetic acid is indicated to identify and perform biopsy to confirm the finding. Few studies show the follow-up of patients treated with anal HPV induced lesions. We are using both methods in association and subclinical lesions have been found in 50 percent of patients, whose proctological examinations are free from HPV lesions. However, some smears have cytological alterations, despite anal colposcopy being normal. The aim of this study was to observe these lesions' behavior in a six-month follow-up, during a year, and to assess whether this periodicity of re-evaluations was enough to avoid high grade or superior lesions. We have found 58 (21 percent) among 273 patients with these parameters. One year re-evaluations of 22 of the patients showed that anal colposcopies remained normal in 17 (74 percent). In five (22 percent), the cytology returned to normality and in 12 (52 percent), the same abnormality was seen. The other six patients (26 percent) developed clinical or subclinical HPV induced lesions. T CD4+ lymphocytes counts of HIV-positive patients were inferior in those whose lesions progressed. These results permitted us to conclude that cytological alterations can progress or clear in these patients, and they have close relationship with the immunity, and the six-month interval is enough to each re-evaluation.

The action mechanism of the effects of vitamin E succinate on apoptosis of human oral squamous cancer Tca 8113 cells / 肿瘤

Objective: To investigate the effect of vitamin E succinate (VES) on apoptosis of Tca 8113 human oral squamous carcinoma cells and its action mechanism. Methods: Flow cytometry was applied to determine the effect of VES on cell cycle distribution and apoptosis after PI staining or Annexin V/PI double staining. The expression of Bax mRNA was quantified by RT-PCR. The relative amounts of the Bax protein was measured by Western blotting. Results: VES significantly inhibited the growth of Tca8113 cells, induced typical apoptosis, and up-regulated the expression of Bax mRNA and protein. After 24 h the apoptotic rate reached the peak level. Conclusion: VES induces apoptosis of Tca8113 human oral squamous carcinoma cells, which is probably related with up-regulation of Bax expression.

Expressions of TNFR1,TNFR2 and TRAF2 in laryngeal squamous carcinoma / 吉林大学学报(医学版)

0.05),and TRAF2 was related to the tumor grade only(P