Human Cervix Uteri Research Articles

Synthesis of an Aryl-Semicarbazone-Based Cu(II) Complex for DNA and BSA Interaction and Anti-Cancer Activity against Human Cervix Uteri Carcinoma

The current study provides an in-depth analysis of the biological properties of a Cu(II) complex (C22H24Cu2N6O10) obtained from an aryl-semicarbazone ligand derived (L) from the condensation of 2,4-dihydroxy acetophenone and semicarbazide. The binding behavior of this complex with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein was explored using a combination of experimental and theoretical approaches. The results suggest that the complex binds with CT-DNA via a partial intercalation, and hydrophobic interaction. However, the complex binds to BSA protein predominantly through hydrogen bonding or van der Waals interactions rather than hydrophobic interactions. The molecular docking methodology was carried out to substantiate the experimental finding. Furthermore, the in vitro cytotoxicity study was conducted on human cervix uteri carcinoma (SiHa cancerous cell) lines upon exposure to the complex, and the findings reveal a considerable decrease in cell viability, when compared to the control. Overall, this study provides a comprehensive understanding of the biological potential of the Cu(II) complex and its potential as an anti-cancer agent.

Biophysical insights into the binding capability of Cu(II) schiff base complex with BSA protein and cytotoxicity studies against SiHa

Herein, we have explored the effects of chlorinated mononuclear Cu(II) complex upon binding with BSA protein (bovine serum albumin) and its in vitro anti-proliferative potentiality against SiHa cell. The complex was synthesized involving a Schiff base ligand having N,N,O donor centers and characterized by several spectroscopic studies. Structure, DFT studies and Hirshfeld surface (HS) analyses were identified using crystallographic computational studies. The binding interaction with BSA depicts the efficacy of the complex towards promising binding of it with BSA. Further, the complex shows a moderate cytotoxicity against SiHa cancer cell signifying its potentiality as an anti-proliferative agent for human cervix uteri carcinoma.

Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. Methods. Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)—the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. Results. The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers’ controls (τ = 0.18 p = 0.40). Conclusion. The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression.

Trans-Mucosal Efficacy of Non-Thermal Plasma Treatment on Cervical Cancer Tissue and Human Cervix Uteri by a Next Generation Electrosurgical Argon Plasma Device.

Non-invasive physical plasma (NIPP) generated by non-thermally operated electrosurgical argon plasma sources is a promising treatment for local chronic inflammatory, precancerous and cancerous diseases. NIPP-enabling plasma sources are highly available and medically approved. The purpose of this study is the investigation of the effects of non-thermal NIPP on cancer cell proliferation, viability and apoptosis and the identification of the underlying biochemical and molecular modes of action. For this, cervical cancer (CC) single cells and healthy human cervical tissue were analyzed by cell counting, caspase activity assays, microscopic and flow-cytometric viability measurements and molecular tissue characterization using Raman imaging. NIPP treatment caused an immediate and persisting decrease in CC cell growth and cell viability associated with significant plasma-dependent effects on lipid structures. These effects could also be identified in primary cells from healthy cervical tissue and could be traced into the basal cell layer of superficially NIPP-treated cervical mucosa. This study shows that NIPP treatment with non-thermally operated electrosurgical argon plasma devices is a promising method for the treatment of human mucosa, inducing specific molecular changes in cells.

The Effect of Flavonoids on Cancer and Normal Cell Lines invitro

This study was aimed to know the inhibitory effect of the flavonoid extract of Silybum marianum seeds on two of the cancer cell lines , human brain cancinoma(AMGM), human cervix uteri epitheloid carcinoma (Hela ) and one normal cell line , Mouse embryonic fibroblast cell line (MEF). The concentration was (1000,500,250,125,62.5) µg/ml respectively with two exposure time (24 & 48) hours for the cancer cell lines and one exposure time (48) hr. for the normal one .The results showed that flavonoids extract has obvious inhibitory effect on (human brain carcinoma & Hela) with (P<0.05) significantly in high concentration (1000) µg/ml the cellular density (obsorption) of human brain carcinoma was (0.052) with inhibitory ratio (39%) compared with control , At 48 hours exposure the density was (0.051) with inhibitory ratio (94%) compared with control , whereas the density in Hela was (0.059, 0.06) with inhibitory ratio85.7% and 86% respectively at 24 and 48 hr. exposure .While the normal cell line showed no signification effect (P<0.05) for all brevious concentration except the high one (1000) µg/ml , whereas the density of MEF was (0.23), with inhibitory effect (34%) .The result of this study has indicated ahighest inhibitory activity of the cancer cell lines for both AMGM & Hela .

Chemical Composition and Antiproliferative Activity of Senecio Leucanthemifolius Poiret Essential Oil

Our work consisted in evaluating the in vitro cytotoxicity of Senecio leucanthemifolius Poiret essential oil. This oil was extracted by Hydrodistillation followed by a liquid /liquid extraction (water/ ethyl acetate). The chemical composition was determinated by gas chromatography-mass spectrometey (CG-MS). The major compounds which characterize this plant are α-Hydroxy-p-cymen (27.3 %), carvacrol (12.2 %), nerol (10.9 %) carveol (9.2 %) and cis-α-bisabolene (7.0 %). The cytotoxicity was evaluated through the use of a human cervix uteri cancerous cellular line (HeLa cell line). Essential oil showed an important cytotoxic activity against the cancer cells with an IC50 = 1.158 μl/ml.

Changes in uterine innervation in pregnancy and during labour

The present review highlights recent findings focusing on effects on the cervical innervation exerted by term pregnancy and labour. The corpus uteri is almost denervated in term pregnancy, as demonstrated in both humans and rodents, whereas the cervical innervation remains dense throughout pregnancy and labour. In rats, fewer connections between sensory subdivisions in spinal cord segments and the cervix have been observed in late pregnancy as compared with the nonpregnant state. In term pregnancy an increased excitability of mechanosensitive afferents innervating the cervix has been demonstrated. The reasons for these seemingly contradictory findings may be clarified in further studies. Transient receptor potential vanilloid receptor, a key molecule in nociception, has been identified in the human cervix uteri in the nonpregnant state and during pregnancy and labour as opposed to the corpus, in which transient receptor potential vanilloid receptor disappears during pregnancy. These findings add evidence to the hypothesis that the uterine cervix is the main site from where labour pain propagates. The conservation of the cervical innervation in term pregnancy and labour, in contrast to the corpus, and the large number of mediators involved in cervical ripening clearly indicate that the cervix plays a crucial role in pregnancy maintenance, labour initiation, labour pain and parturition.

A STUDY OF THE INHIBITORY EFFECT OF THE CAPAR, CAPPARIS SPINOSA L. AQUEOUS CRUDE LEAF EXTRACT ON THE HEP-2 AND HELA CANCER CELLS LINES

This study was conducted to know the inhibitory effect of the crude aqueous Capar, Capparis spaniosa leaf plant on two cellular cancer lines human epidermoid larynx carcinoma Hep-2 and human cervix uteri epitheloid carcinoma Hela . Four leaf extract concentrations have been used (125, 250,500 and1000) μg/ml and the exposure time was (48 and 72) hrs . This study indicated a clear significant inhibitory effect (p>0.001) of the extract on the cancer lines ,Hep-2 and Hela ,even with the first low concentration .The cellular Hep-2 density was (0.340%) , whereas the density in Hela was (0.6545%) at the lowest concentration 125 μg / ml . The highest inhibitory effect of the extract was at (1000) μg/ml ,the cellular Hep-2 density (0.108%) and in Hela (0.266%) . The highest significant inhibitory effect of the extract (72) hrs of exposure time was (0.275%) Hep-2 and (0.4624%) Hela .The result of this study has indicated ahighest inhibitory activity of the aqucous leaf extract of Cpparis Spinosa on the density average of cancer cells for both Hep-2 and Hela . There was an inversely linear relation ship between exposure time and concentration on the growth of cells . As exposure time and concentrations have increased , the killed cells have increased also .

Influence of pregnancy and labor on the occurrence of nerve fibers expressing the capsaicin receptor TRPV1 in human corpus and cervix uteri

BackgroundCervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1.MethodsWe have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 8) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 8). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments/peripherin).ResultsIn cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus.ConclusionIn this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with cervical ripening and labor. Furthermore, these data support the concept that cervix uteri may be the major site from which labor pain emanates. Our findings also support the possibility of developing alternative approaches to treat labor pain.

Presence of sensory nerve corpuscles in the human corpus and cervix uteri during pregnancy and labor as revealed by immunohistochemistry

BackgroundThe uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed.MethodsBiopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100.ResultsStructures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP 9.5 and S-100. They were observed in specimens of the non-pregnant corpus and cervix and also in specimens of the pregnant cervix before onset of labor. However, they were absent in all specimens during labor.ConclusionSensory corpuscles have here for the first time been detected in the human corpus and cervix uteri. Studies on the importance of the corpuscles in relation to the protective reflex actions that occur in the uterus during pregnancy should be performed in the future.

Preparation of bioelectret collagen and its influence on cell culture in vitro

Collagen extracted from pigskin was corona-charged negatively by a specifically designed device. Different charging voltages, temperatures and times were applied to prepare collagen bioelectret. The decline of the surface potential of the bioelectret under different treatment was then determined. The data showed that the surface potential was markedly varied with the charging conditions. The optimal values of three parameters for charging collagen coatings were defined as follows: voltage, 8 KV; temperature, 40 degrees Celsius; time, 25 min. Treatment of the bioelectret with distillated water, or saline solution (0.9%) or culture medium induced a sharp decrease of the surface potential. In addition, we investigated the effects of the charged collagen on cell growth and intracellular calcium level of three types of cultured mammalian cell lines, including Chinese hamster ovary CHO cells, human cervix uteri tumor HeLa cells and human promyelocytic HL-60 cells. Cell growth and the intracellular calcium level were determined by MTT reagent-based assay and a fluorescent probe Fura-2, respectively. The results showed that negatively charged collagen stimulated the growth of CHO or HL-60 cell line but inhibited the growth of HeLa cell line. Furthermore, after attaching to the charged collagen, the intracellular calcium level of CHO cells increased, while that of HeLa cells decreased. Thus we proposed for the first time that collagen bioelectret could differentially modulate the growth of different cells, by an unknown mechanism that probably involves a role of intracellular calcium.

Unaltered innervation of the human cervix uteri in contrast to the corpus during pregnancy and labor as revealed by PGP 9.5 immunohistochemistry

Objective To examine the occurrence of the general neuronal marker protein gene product 9.5 (PGP 9.5) in the human corpus (isthmus region) and the cervix uteri during pregnancy and parturition Study design Biopsies were taken from the upper edge of the hysterotomy during caesarean section (CS) at term ( n = 5), in labor ( n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy ( n = 5). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostate sections were prepared for immunohistochemistry using polyclonal antibodies to PGP 9.5. Results Nerve fibers displaying PGP 9.5 immunoreactivity were observed in all sections from the three groups examined. They were identified in muscle tissue, in the stroma, and around blood vessel walls. A 30-fold decline of immunoreactive nerve fibers was observed in the isthmus part of the corpus uteri at term compared to the non-pregnant. There were no significant differences between the immunoreactivity in the cervix uteri of the three groups Conclusions The innervation of the cervix uteri is dense and unaltered throughout pregnancy and labor. In contrast, the corpus is almost denervated. Further studies are needed to clarify the reason and the impact of these findings.

Effects of extracts from sporoderm-broken spores of Ganoderma lucidum on HeLa cells.

The effects of extracts from Ganoderma lucidum spores on the growth of human cervix uteri tumor HeLa cells as well as on the cell cycle and intracellular calcium level were investigated. Alcohol extracts were prepared from sporoderm-broken and sporoderm-nonbroken spores (termed extract I and extract II) of G. lucidum. Extract I was then subjected to silica gel chromatography to obtain extract III. Cytotoxicity was examined by means of trypan blue exclusion and MTT tests. It was found that extract I and extract III, but not extract II strongly inhibited the growth of HeLa cells, and that extract III was more effective than extract I. Moreover, extract III was shown to be capable of blocking the cell cycle at the transition from G1 to S phase and inducing a marked decrease of intracellular calcium level, determined by flow cytometry and the specific fluorescent calcium probe Fura-2, respectively. These results imply that (1) the breaking of G. lucidum spores improves the release of cytotoxic activity and (2) the effective extract might influence the cell cycle and cellular signal transduction by altering the calcium transport system.

Eosinophils in human cervical ripening

Objective: Cervical ripening has many similarities to an inflammatory reaction. Eosinophil granulocytes are involved in several inflammatory responses. The objective was to investigate the presence of eosinophils in human cervix uteri during different conditions. Study design: Cervical biopsies were obtained from non-pregnant ( n = 6), women in early pregnancy ( n = 11) and from three groups of women at term: spontaneous vaginal deliveries ( n = 5); vaginal deliveries after pretreatment with Prostaglandin E 2 ( n = 7); and from women who underwent planned Caesarean section ( n = 7). Immunohistochemical staining for eosinophil granulocytes (ECP, EG 2) were performed. The biopsies were analysed blined. Results: Eosinophils showing degranulation in the tissue were found in all specimens from vaginal deliveries. No eosinophils, or very few were seen in the biopsies from non-pregnant, early pregnant women or planned caesarean section. Prostaglandin treatment had no effect on the results. Conclusion: Eosinophils participate in cervical ripening at term in women, and seem to arise mainly after labour.

Ultrastructural Study of the Nuclei of Normal, Dysplastic, and Carcinomatous Epithelial Cells of the Human Cervix Uteri

The nuclei of epithelial cells of the uterine cervix of normal women and of patients with various degrees of dysplasia, carcinoma in situ, and invasive carcinoma were studied by means of electron microscopy. Nuclear ribonucleoprotein components and chromatin were contrasted using preferential methods for RNA and DNA. Changes in the distribution of the extranucleolar ribonucleoprotein-containing structures were found, ranging from low-grade dysplastic lesions to invasive carcinoma. Compared with normal epithelial cells, dysplastic and neoplastic cells possess more nuclear bodies, as well as deep invaginations of the nuclear envelope and lobulations. Morphometric parameters estimated were nuclear volume, numerical density of perichromatin granules (PCG), and fraction of nuclear volume occupied by compact chromatin. The pattern of values of these parameters in the cell layers of normal cervical epithelium was disrupted in all the lesions. These data suggest that the processes studied induce early alterations in transcription and processing and/or exportation of mRNA to the cytoplasm. Two populations of cells were found in invasive carcinomas, one with large nuclei, sparse compact chromatin, and few PCG, and the other with small nuclei, abundant compact chromatin, and numerous PCG. Their morphologic features indicate that the former population is composed of relatively undifferentiated cells, while the latter is made up of well-differentiated cells which could be neoplastic or entrapped normal cells.

Double minute chromatin bodies in carcinoma of the human cervix uteri

In direct G-banded preparations of 150 cases of cervical cancer, double minutes (dmin) were observed in 43% (64 cancers) of the patients, including a case of carcinoma-in-situ (CIS). The incidence of dmin varied from 1 to over 20 per cell. The karyotypic findings in the tumors containing dmin did not reveal any similarities and the prognosis of the patients with dmin was significantly worse compared to those without dmin. The presence of dmin in cytogenetic preparations of primary tumors may indicate a role in the maintenance and/or progression of malignancy, particularly as dmin have been suggested to represent amplified genes.

Estrogen receptor in carcinoma in situ of the cervix.

The lining epithelium of the human cervix uteri is an estrogen dependent tissue containing specific intracellular receptors for this hormone. However, the influence of estrogen on an early neoplastic lesion arising from this epithelium, such as carcinoma in situ of the cervix, has not been determined. We evaluated 24 formalin fixed paraffin embedded tissue specimens of cervical carcinoma in situ for the presence of estrogen receptor by the immunoperoxidase technique. The antigenic sites of estrogen receptor were exposed by DNAse treatment followed by peroxidase-antiperoxidase (PAP) staining with monoclonal antibody against estrogen receptor. Parallel negative controls were run using negative control antibody and rat serum. Quality control for positive staining was performed using breast cancer tissue sections from specimens with known estrogen receptor detected by the radioreceptor method. Strongly positive staining was observed in all specimens in the nuclei of glandular epithelium, stromal cells, and basal and parabasal cells. However, nuclei within carcinoma in situ of the cervix showed no evidence of positive staining. Due to lack of specific intracellular receptor for estrogen, it appears that carcinoma in situ of the cervix will not be under direct influence of estrogen.

Collagenase activity in the human cervix uteri after prostaglandin E 2 application during the first trimester

Cervix biopsies were obtained during the first trimester from plurigravidae and primigravidae at various times after intracervical application of prostaglandin E 2. The tissues were extracted with Ca 2+-containing buffer, and collagenase activity was determined in these extracts using a solid phase assay in which triple helical 125I-labelled collagen was cleaved. Collagenase was detected in all samples but elevated activity was present only during a short temporal window after prostaglandin application. Maximal activity was observed 1 and 2 h after application of prostaglandin in multigravidae and 4 h in primigravidae. These data can explain why collagenase activity in cervical tissues after prostaglandin application had previously not been found. They indicate somewhat different mechanisms of cervical ripening in primigravide compared to multigravidae.

Glutathione S-transferase (placental) as a marker of transformation in the human cervix uteri: an immunohistochemical study

Using an indirect immunohistochemical technique on paraffin sections, employing a polyclonal antibody to the acidic (placental) form of glutathione-S-transferase (GST), we have evaluated cytoplasmic and nuclear staining in a series of 67 cervical biopsies including normal non neoplastic tissue, immature squamous metaplasia, all grades of cervical intraepithelial neoplasia (CIN) and invasive carcinomas of keratinising and non-keratinising types. No differences in cytoplasmic staining between the varied lesions studied were seen. However, there were marked differences in nuclear staining. While normal non-neoplastic stratified squamous epithelium showed weak staining of the lower one-third of the epithelium only, in immature squamous metaplasia and in all grades of CIN there was intense nuclear staining in all layers of the epithelium. Invasive carcinomas showed generally less intense nuclear staining than CIN lesions. Endocervical cell nuclei also showed intense nuclear staining. These findings indicate that GST is of limited use as a marker of transformation in the human cervix uteri.

Changes in the connective tissue of corpus and cervix uteri during ripening and labour in term pregnancy.

The composition of the connective tissue of human cervix and corpus uteri was studied in tissue specimens from seven nonpregnant women and 14 pregnant women, delivered at term by section, to examine spontaneous cervical ripening and labour-induced changes in both the uterine and the cervical connective tissue. The main finding in both the cervix and the corpus was a large (40-60%) decrease of the collagen concentration. The collagen extractability, obtained by pepsin digestion, was increased twofold, suggesting a change of the organization of the collagen fibrils. This reorganization process could also be demonstrated by a large increase of the collagenolytic activity demonstrated with an artificial DNP-peptide substrate. The concentrations of sulphated glycosaminoglycans was lower in pregnant women than in non-pregnant women. The results show that both the cervix and the corpus uteri contain substantial amounts of connective tissue components (collagen, sulphated glycosaminoglycans and hyaluronic acid) and that during ripening, reconstruction of the connective tissue components occurs in both sites. This indicates that the cervical state reflects that of the myometrium.