Antioxidant and Antiproliferative Activity of The Ethanolic Extract of Equisetum Myriochaetum and Molecular Docking of Its Main Metabolites (Apigenin, Kaempferol, and Quercetin) on ß-Tubulin.

Equisetum myriochaetum is a semi-aquatic plant found on riverbanks that is commonly used in traditional medicine as a diuretic agent. Additionally, the genus Equisetum stands out for its content of the flavonoid kaempferol, a well-known antiproliferative agent. Therefore, in this study, E. myriochaetum ethanolic extract was tested in vitro against a cervical cancer cell line (SiHa). Additionally, the antioxidative activity was evaluated through a 2,2-diphenyl-1-picrilhidrazil (DPPH) assay. Finally, a molecular docking analysis of apigenin, kaempferol, and quercetin on the active site of ß-tubulin was performed to investigate their potential mechanism of action. All fractions of E. myriochaetum ethanolic extract showed antioxidative activity. Fraction 14 displayed an antiproliferative capacity with a half maximal inhibitory concentration (IC50) value of 6.78 µg/mL against SiHa cells.

Topographical binding to mucosa-exposed cancer cells: pollen-mimetic porous microspheres with tunable pore sizes.

Mucoadhesives have been perceived as an effective approach for targeting the mucosa-associated diseases, which relied on the adhesive molecules to enhance the specificity. Here, topographical binding is proposed based on the fabrication of surface pore size tunable pollen-mimetic microspheres with phase separation and electrospray technology. We proved that microspheres with large-pores (pore size of 1005 ± 448 nm) were the excellent potential candidate for the mucoadhesives, as they not only possessed better adhesion ability, but also could topographically bind cervical cancer cells. Our methods of topographical binding offered a new way of designing the mucoadhesives for treating the mucosa-associated diseases.

Quantitative diagnosis of cervical neoplasia using fluorescence lifetime imaging on haematoxylin and eosin stained tissue sections.

The use of conventional fluorescence microscopy for characterizing tissue pathological states is limited by overlapping spectra and the dependence on excitation power and fluorophore concentration. Fluorescence lifetime imaging microscopy (FLIM) can overcome these limitations due to its insensitivity to fluorophore concentration, excitation power and spectral similarity. This study investigates the diagnosis of early cervical cancer using FLIM and a neural network extreme learning machine classifier. A concurrently high sensitivity and specificity of 92.8% and 80.2%, respectively, were achieved. The results suggest that the proposed technique can be used to supplement the traditional histopathological examination of early cervical cancer.

Effect of temperature on surface properties of cervical tissue homogenate and organic phase monolayers.

The temperature dependence of Langmuir monolayers of normal and cancerous human cervical tissues and their organic phases between temperatures of 37 and 45 degrees C was evaluated. Analysis of the surface pressure-area isotherms revealed significantly different increase in fluidity of the cancerous cervical tissue monolayer at 42 degrees C as opposed to the normal cervical tissue monolayers (p<0.05). Similarly, in the case of cervical cancerous organic phase monolayers significant increase of fluidity was observed at 40 degrees C whereas no such change was observed in the normal cervical organic phase monolayers. The effect of temperature was found to be different in cancerous and normal cervical tissues and this may be due to the different lipid profiles in them. Cancerous cervical tissues had 1.8-fold higher total lipids as compared to the normals. Similarly, the PC, PE, PI, PG, SM and PS levels in cancerous cervical tissues were 3.6, 2.0, 2.3, 4.7, 1.7 and 2.2 times higher than those of normal cervical tissues, respectively. Significant cancer-normal difference in minimum surface tension and hysteresis area was found at all temperatures studied for both tissue homogenates and organic phases. For example, cancerous tissue homogenates showed minimum surface tensions of 51.9+/-4.6, 54.4+/-5.9, 57.6+/-6.0 and 51.9+/-5.6mN/m at temperatures 37, 40, 42 and 45 degrees C whereas the corresponding values for normal cervical tissue homogenates were 39.3+/-3.6, 39.2+/-3.7, 39.2+/-3.8 and 39.1+/-3.6, respectively. The fluidity change at hyperthermic range of temperature can be correlated to the increased efficiency of drug on combination therapy with hyperthermia. These results may have implications in manipulating the fluidity of cervical cancer tissue membranes for better permeability thereby leading to better therapeutic strategies for cervical cancer.

Observations of high iron diamine-alcian blue stain in uterine cervical glandular lesions.

We studied epithelial glycoproteins in uterine cervical lesions, including glandular lesions, and investigated whether a more accurate diagnosis could be obtained using high iron diamine-alcian blue (HID-AB) stain and immunostaining with carcinoembryonic antigen (CEA). In addition, we examined the usefulness of preoperative diagnosis using biopsy specimens stained with HID-AB and CEA. Normal endocervical glands showed a predominance of sulfomucin, while adenocarcinoma predominantly showed sialomucin. CEA was highly detected in adenocarcinoma, but not in normal endocervix or in glandular dysplasia, suggesting that this stain has high specificity. The staining patterns of biopsy specimens and hysterectomy specimens were similar. Therefore HID-AB stain and CEA stain may be useful as a supplementary means of diagnosing uterine cervical lesions.

Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis-retinoic acid/interferon.

PURPOSE: We have evaluated the tumor tissue pO2 in cervical cancers during radiotherapy with special emphasis on the course of the pO2 in primarily hypoxic tumors and in patients treated with radiotherapy plus 13-cis-retinoic acid/interferon-alpha-2a. METHODS AND MATERIALS: From June 1995 through April 1997, 49 patients with squamous cell carcinoma FIGO IIB-IVA of the cervix who were treated with definitive radiotherapy with curative intent underwent polarographic measurement of tumor tissue pO2 with an Eppendorf pO2-histograph prior to and during radiation treatment. Radiotherapy consisted of external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus high dose rate (HDR) brachytherapy. Twenty-two patients had additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) and interferon-alpha-2a (IFN-alpha-2a). Therapy with cRA/IFN in these patients started 2 weeks before radiotherapy; during this induction period, cRA was administered in a dosage of 1 mg per kilogram body weight orally daily and IFN-alpha-2a in a dosage of 6x10(6) I.U. subcutaneously daily. After start of external radiotherapy (XRT), cRA/IFN was continued concomitantly with radiotherapy in reduced doses (0.5 mg cRA per kg body weight orally daily plus 3x10(6) I.U. IFN-alpha-2a subcutaneously three times weekly until the end of the radiation treatment). PO2 measurements were performed prior to radiotherapy, at 20 Gy, and at the end of radiotherapy. RESULTS: A poor oxygenation defined as a median pO2 of 10 mm Hg or less was present in 15/38 tumors (39%) in which measurements prior to any treatment were done. Low pO2 readings below 5 mm Hg were present in 70% of all tumors prior to treatment. In 13 of 15 hypoxic tumors, pO2 measurements at 19.8 Gy were performed. In these tumors, a significant increase of the median pO2 from 6.0+/-3.1 mm Hg to 20.7+/-21.2 mm Hg was found, p<0.01. The increase in the median pO2 was more pronounced in patients with radiotherapy plus additional cRA/IFN treatment as compared to patients treated with irradiation alone (median pO2 raised from 7.0+/-3.5 mm Hg to 40.9+/-21.3 mm Hg versus 5.7+/-3.1 mm Hg to 14.7+/-17.9 mm Hg). In a multivariate analysis, both the effect of radiation dose (pretreatment versus 19.8 Gy) and the type of treatment (XRT alone versus XRT plus cRA/IFN) had significant impact on the pO2 (P = 0.003 and p = 0.04). In patients with well-oxygenated tumors (pretreatment median pO2>10 mm Hg), 20/23 (87%) achieved a clinically complete response. In patients with primarily hypoxic tumors, 6/6 patients whose primarily hypoxic tumors showed an increase of the median pO2 above 10 mm Hg at 19.8 Gy achieved a complete remission (CR). In contrast, only 4/7 patients with a low pretreatment and persisting low median pO2 achieved a CR. CONCLUSIONS: There are evident changes in the oxygenation of cervical cancers during a course of fractionated radiotherapy. In primarily hypoxic tumors, a significant increase of the median pO2 was found. An additional treatment with cis-retinoic acid/interferon further improved the oxygenation. An impact of the different patterns of oxygenation on local control is to be evaluated.

[Relation between selenium and cancer of uterine cervix].

Selenium (Se) concentration in serum, hair, normal cervix tissue or tissue of cervix cancer of 20 cases with cancer of uterine cervix (survey group), 21 with myoma of the uterus and 1 with cervical polys (control group), but also in rice, water and soil in the high and low incidence areas of cervical cancer was determined. The results showed that Se concentration in serum and cancer tissue of uterine cervix in patients with cancer of uterine cervix was significantly lower than that in the control group (P < 0.05), but no significant difference of Se concentration in hair was observed (P > 0.05), However Se concentration in rice, water and soil in the high incidence areas of cervical cancer was significantly lower than that in the low incidence areas (P < 0.05). Se deficiency may play a role in the carcinogenesis of uterine cervix.