Carcinoma Of Uteri Research Articles

Radical radiotherapy in patients with cervix uteri carcinoma: experience of Ondokuz Mayis University

BackgroundRadical radiotherapy is the standard treatment for patients with locally advanced cervix uteri carcinoma (FIGO stage IB2–IVA). Worldwide, incidence and mortality rates vary among regions because of differences in lifestyles and treatment standards. Herein, we evaluated the outcomes of radical radiotherapy in patients with locally advanced cervix uteri carcinoma from the middle Black Sea region of Turkey.MethodsWe retrospectively reviewed the records of 64 consecutive patients with locally advanced cervix uteri carcinoma who were treated from January 2013 to 2016 in our radiation oncology department. All patients staging and radiotherapy planning were performed with modern imaging techniques including magnetic resonance imaging and positron-emission-tomography/computed tomography before radical radiotherapy. Thereafter, all of them were treated with external beam radiotherapy and concurrent cis-platinum-based chemotherapy followed by three-dimensional intra-cavitary high-dose-rate brachytherapy.ResultsThe median age at diagnosis was 54.5 years. The median follow-up period was 21 months. Acute grade 3 toxicity was detected in 3.1% of patients. Late toxicity was not detected in any patient. The 1- and 3-year progression-free survival rates were 83.6 and 67.5%, respectively. The 1- and 3-year overall survival rates were 95.7 and 76.9%, respectively. The most important prognostic factor was the FIGO stage. Distant metastasis was the most common cause of death in patients with locally advanced cervix uteri carcinoma despite radical radiotherapy.ConclusionsIn patients with locally-advanced cervix uteri carcinoma from the middle Black Sea region of our developing country, acceptable toxicity and survival rates are achieved similar to the recent literature from developed countries with using of modern staging, planning and radical radiotherapy techniques. However, recurrence was mostly in the form of distant metastases and further investigations on systemic therapies are required.

Endometrial carcinoma in a gravid uterus: a case report and literature review

BackgroundEndometrial carcinoma (EC) is rarely diagnosed during pregnancy. Therefore, the histopathological findings, clinical course, and gross appearance of the resected uterus during pregnancy are not well known. We present a case of EC diagnosed during pregnancy. In addition, we reviewed the literature dating from January 1995 to March 2019 for cases of EC diagnosed during pregnancy and within 15 months after pregnancy, and we discussed this topic to improve the understanding of this rare condition.Case presentationA 35-year-old woman underwent an urgent cesarean delivery in gestational week 35 due to antepartum bleeding caused by placenta previa. Hysterectomy was performed with the diagnosis of placenta accreta spectrum (PAS). Remarkably, the postoperative gross and histopathological examinations revealed an endometrioid adenocarcinoma (grade 1). The histopathological findings revealed a pattern similar to that of EC not related with pregnancy. Immunohistochemistry revealed an overexpression of the estrogen and progesterone receptors; however, the p53 expression was negative. We performed laparoscopic bilateral salpingo-oophorectomy and pelvic lymphadenectomy 102 days after the cesarean hysterectomy, and confirmed surgical stage IA without metastases. Our patient has had no recurrence in 4 years after the cesarean delivery.An electronic search of the literature revealed 25 cases of EC (including our case) diagnosed during or after pregnancy. Sixteen of the 25 patients were diagnosed after abortions in the first trimester, 9 were diagnosed within 14 months of childbirth, and our case was the first with diagnosis from a surgical specimen of peripartum hysterectomy due to the PAS. In 23 of the 25 cases endometrioid adenocarcinoma grade 1 to 2 was found, and it seemed to have a good prognosis.ConclusionThe present findings suggest that careful examination of a resected uterus is essential, even when surgery is performed for an obstetric indication. Our case is an extremely rare case of EC during pregnancy; the histopathological pattern was similar to that of typical EC, and no recurrence was noted. The high levels of estrogen and progesterone during pregnancy did not seem to promote tumor progression in our case.

New 2,6-diaminopyridines containing a sterically hindered benzylphosphonate moiety in the aromatic core as potential antioxidant and anti-cancer drugs

A series of 2,6-diaminopyridines was synthesized for the first time, containing phosphoryl sterically hindered phenolic fragments in the aromatic core. The antioxidant activity of these compounds was investigated, 2,6-diaminopyridine derivatives were shown to exhibit higher activity in comparison with their structural analogues. For dialkyl/diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonates, their structural analogues based on meta-phenylenediamine, phosphorus-containing sterically hindered phenols and the corresponding cyclohexadienones cytotoxicity against tumor lines of epithelioid carcinoma of the cervix uteri (M-Hela) and breast adenocarcinoma (MCF-7) has been studied in vitro, as well as on normal human Chang liver cell lines. Diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonate was shown to be the most active against the epithelioid line M-Hela - IC50 comprises 7.4 μM. It was shown that apoptosis induced by the lead compound proceeds along the internal pathway of caspase-9 activation. It was established that all studied compounds do not possess hemolytic activity.

Current FIGO Staging for Carcinoma of the Cervix Uteri and Treatment of Particular Stages.

Here, we present a review of the revised FIGO (International Federation of Gynecology and Obstetrics) staging system for carcinoma of the cervix uteri, explaining the reasons for the changes and summarizing suitable diagnostic methods and treatment options for particular stages of disease according to current guidelines. The FIGO staging system has been revised as follows. Measurement of lateral extension has been removed from stage IA; the only criterion is a measurement for the deepest invasion of < 5.0 mm. Stage IB has been divided into three subgroups: IB1, tumors with a largest diameter measuring 5 mm and < 2 cm; IB2, tumors measuring 2-4 cm; IB3, tumors measuring 4 cm. Stage IIIC includes an assessment of retroperitoneal lymph nodes: IIIC1 if only pelvic lymph nodes are involved, and IIIC2 if para-aortic nodes are infiltrated. The revised staging system does not mandate the use of a specific imaging method or surgical assessment of the extent of the tumor. The method used to assign a stage should be recorded and reported. The European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology, and the European Society of Pathology have developed clinically relevant and evidence-based guidelines to improve the quality of care for women with cervical cancer. These guidelines cover comprehensive staging, management, and follow-up for patients with cervical cancer. The guidelines are intended for use by gynaecologic oncologists, general gynaecologists, surgeons, radiation oncologists, pathologists, clinical oncologists, radiologists, general practitioners, palliative care experts, and other health professionals. We summarize the new FIGO classification system, including diagnostic methods and treatments for particular stages. We also discuss the main changes and their clinical impact. This work was supported by the Charles University project UNCE 204065. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Tissue HE4 Expression Discriminates the Ovarian Serous Carcinoma but Not the Uterine Serous Carcinoma Patients. A New Adjunct to the Origin of the Tumor Site.

Both uterine serous carcinoma (USC) and ovarian serous carcinoma (OSC) are presented at advanced stage at the first admittion and dissseminated disease makes the anatomical site of the tumor origin imposible. CA125 and p53 are reliable markers that are useful for differentiating both uterine serous and ovarian serous carcinoma from their most common subtypes (endometrioid type carcinoma of ovary and uterus) but so far there is no histopathologic marker that differentiates USC from OSC. On the other hand, Trastuzumab (Herceptin) increases progression-free survival among USC patients, but not OSC patients and makes the histopathologically assigning the origin of the tumor important. So, the aim of this study was to evaluate the immunohistopathological discriminative value of the human epididymis secretory protein 4 (HE4) between OSC and USC patients. Patients with a diagnosis of OSC and UTC were enrolled. HE4 expression was evaluated by immunohistochemistry. The results were compared between groups. Of the tumor tissues studied, HE4 immunostaining was seen in the majority of ovarian serous carcinoma cases (89.65%), while endomatrial serous carcinoma cases were devoid of HE4 immunostaining. HE4 immunostaining was seen in 39.1% uterin serous carcinoma cases and this difference was statistically significant (p = 0.001). Our study demonstrated for the first time the potential of HE4 expression to predict the anatomical site of tumor origin. HE4 is a novel tumor marker that differentiates USC from OSC.

Revised FIGO staging for carcinoma of the cervix uteri.

To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent. Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations. In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5mm and <2cm in greatest diameter; stage IB2: tumors 2-4cm; stage IB3: tumors ≥4cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care. The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions.

Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis

BackgroundCarbon-ion radiotherapy (C-ion RT) provides better dose distribution in cancer treatment compared to photons. Additionally, carbon-ion beams provide a higher biological effectiveness, and thus a higher tumor control probability. However, information regarding the dose constraints for organs at risk in C-ion RT is limited. This study aimed to determine the predictive factors for late morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus carcinomas.MethodsBetween June 1995 and January 2010, 134 patients with uterus carcinomas were treated with C-ion RT with curative intent; prescription doses of 52.8–74.4 Gy (relative biological effectiveness) were delivered in 20–24 fractions. Of these patients, 132 who were followed up for > 6 months were analyzed. We separated the data in two subgroups, a 24 fractions group and a 20 fractions group. Late morbidities, proctitis, and cystitis were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The correlations of clinical and dosimetric parameters, V10–V60, D5cc, D2cc, and Dmax, with the incidence of ≥grade 1 morbidities were retrospectively analyzed.ResultsIn the 24 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 32 and 19%, respectively. Regarding the dose–volume histogram data on the rectum, the D5cc and D2cc were significantly higher in patients with ≥grade 1 proctitis than in those without morbidity. In addition, the D5cc for the bladder was significantly higher in patients with ≥grade 1 cystitis than in those without morbidity. Results of univariate analyses showed that D2cc of the rectum was correlated with the development of ≥grade 1 late proctitis. Moreover, D5cc of the bladder was correlated with the development of ≥grade 1 late cystitis.ConclusionsThe present study identified the dose–volume relationships in C-ion RT regarding the occurrence of late morbidities in the rectum and bladder. Assessment of the factors discussed herein would be beneficial in preventing late morbidities after C-ion RT for pelvic malignancies.Trial registrationRetrospectively registered (NIRS: 16–040).

Antiproliferative and Antioxidant Activities of Two Extracts of the Plant Species Euphorbia dendroides L.

Background: These days, the desire for naturally occurring antioxidants has significantly increased, especially for use in foodstuffs, cosmetics, and pharmaceutical products, to replace synthetic antioxidants that are regularly constrained due to their carcinogenicity. Methods: The study in hand aimed to appraise the antioxidant effect of two Euphorbia dendroides extracts using reducing power, anti-peroxidation, and DPPH (1,1 Diphenyl 2 Pycril Hydrazil) scavenging essays, in addition to the anticancer activity against two tumor cell lines, namely C6 (rat brain tumor)cells, and Hela (human uterus carcinoma)cell lines. Results: The results indicated that the ethyl acetate extract exhibited antiradical activity of 29.49%, higher than that of n-butanol extract (18.06%) at 100 µg/mL but much lower than that of gallic acid (78.21%).The ethyl acetate extract exhibits better reducing capacity and lipid peroxidation inhibitory activity compared to n-butanol extract but less than all tested standards. Moreover, the ethyl acetate extract was found to have an antiproliferative activity of more than 5-FU (5-fluoro-Uracil) against C6 cells at 250 µg/mL with IC50 and IC75 of 113.97, 119.49 µg/mL, respectively, and good cytotoxic activity against the Hela cell lines at the same concentration. The HPLC-TOF-MS (high performance liquid chromatography-Time-of-flight-Mass Spectrometry) analyses exposed the presence of various compounds, among which Gallic and Chlorogenic acids functioned as major compounds. Conclusions: The two extracts exhibited moderate anticancer abilities and behaved somewhat as average antioxidant agents. Based on the total phenolics and flavonoids contents, as well as HPLC results, it could be concluded that antiproliferative and antioxidant activities depend upon the content of different phenolics and flavonoids.

Synchronous endometrioid carcinoma of bilateral ovaries and uterus: A case report

Synchronous endometrioid carcinoma of bilateral ovaries and uterus: A case report

Gelatinases A and B and their endogenous regulators in the corpus uteri in squamous cell cervical carcinoma

To investigate the expression of gelatinases A and B (matrix metalloproteinases (MMP 2 and MMP 9) and endogenous regulators of their activity, such as a tissue inhibitor of MMP - TIMP-2 and a Pro-MMP-9 activator - urokinase-type plasminogen activator (uPA) as factors of corpus uteri invasion in squamous cell cervical carcinoma (SCCC). The surgical material obtained after hysterectomy in patients diagnosed with SCCC was examined. RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay were used. In SCCC, the expressions of MMP 2 and MMP 9 were found to be high not only in carcinoma of the cervix uteri but also in the corpus uteri, which makes an additional contribution to the enhanced invasive potential of tumors and may have a prognostic value. In SCCC, the expression of MMP 9 may be induced in the corpus uteri where it was absent in normal conditions. MMP 9 can serve as a marker of an invasive process. In most cases, the activity of uPA in the tumor was significantly higher than that in intact uterine tissue, and the expression of TIMP-2 did not change substantially along the entire length of a tissue band (from the vaginal wall to the uterine fundus), as evidenced by RT-PCR, and was at a low level or absent, as shown by IHC. Impaired regulation of MMP 2 and MMP 9 expressions was found not only at the gene level, but also at post-translational one. The expression of the gelatinases MMP 2, MMP 9 and regulators of their activity is aimed at increasing the tumor destructive (invasive) potential and can occur (be induced) in the intact corpus uteri tissue that is morphologically different from cervix uteri tissue with apparent participation of signaling through an epithelial-mesenchymal interaction. The induced MMP 9 can serve as a marker for invasive potential. The data indicate different tissue functions of MMP 2 and MMP 9. They are important for understanding the role of the gelatinases MMP 2, MMP 9 during carcinogenesis, can have a prognostic value, and affect a therapeutic strategy for patient management.

Phytochemicals of Chrysophthalmum montanum (DC.) Boiss. Roots and Their Antiproliferative Activities Against HeLa and C6 Cell Lines

Pre-fractionation and contemporary spectroscopic analysis provides important clues with regard to synergistic and antagonistic effects as well as biological activities in complex multi-mixtures, especially natural products. Phytochemical contents of the Chrysophthalmum montanum root extracts were analyzed by gas chromatography–mass spectrometry and high performance liquid chromatography–time of flight/mass spectrometry. Furthermore, biological activity of root extract was investigated by antiproliferative efficiencies against human uterus carcinoma and rat brain tumor cells in vitro. The biological activity tests were carried out as dose-dependent assay using a multiwell spectrophotometer. 5-Fluorouracil was used as standard anticancer drug. Total 61 lipophilic components were identified quantitatively from the sub-fraction of n-hexane in which saturated fatty acids (33.06%), unsaturated fatty acids (21.03%) and other organic components (43.35%). Twenty three hydrophilic components, 16 phenolic and 7 flavonoid compounds, were quantified in the hydrophilic sub-fractions obtained from the C. montanum roots. Among the hydrophilic components, the vanillic acid was analyzed as 46.463 ± 0.167 mg compound/g dry extract in the sub-fraction dichloromethane. The linoleic acid was analyzed as a substantial component (8.13%) in the sub-fraction n-hexane. The highest antiproliferative activities were obtained from the sub-fraction dichloromethane against HeLa cells (IC50 = 36.53 μg/mL) and the sub-fraction n-hexane against C6 cells (IC50 = 11.98 μg/mL). No cytotoxic effect was observed from these sub-fractions.

Efficacy of combined treatment of experimental tumors with cytostatic agents and GMDP-A

Objective of the study. To evaluate the pharmacological effects of N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-glutamic acid (GMDP-A) as a modifier of biological reactions, i. e. to study its modifying action in regard to traditional cytostatic chemotherapy. Materials and methods. The used drug agents were GMDP-A, cisplatinum, gemcitabine, cyclophosphamide, 5-fluorouracil. The transplanted murine tumors were Р-388 lymphocytic leukemia and S-37 sarcoma (solid and ascites variants), B-16 melanoma, CC-5 squamous cell carcinoma of the cervix uteri, C-26 adenocarcinoma of the colon, and AKATOL carcinoma of the colon (solid tumor variants). Efficacy indices were inhibition of tumor growth, and increase of life span of animals. Results. In the models of transplanted tumors in conventional mice, the influence of GMDP-A has been studied on therapeutic efficacy of cisplatinum (Р-388, S-37, В16, CC-5), 5-fluorouracyl (C-26, AKATOL), gemcitabine and cyclophosphamide (P-388) by using variations in single and total doses, time of the start of the treatment, as well as the route and site of the injection. It has been shown that GMDP-A has modified the efficacy of some cytostatic agents (cisplatinum, gemcitabine and cyclophosphamide) enhancing their antitumor activity irrespective of the location of the site of injection in regard to the tumor node. Conclusion. The obtained results proved the potency of GMDP-A as a modifier of biological reactions.

Bioactivity–guided isolation of flavonoids from Cynanchum acutum L. subsp. sibiricum (willd.) Rech. f. and investigation of their antiproliferative activity

Cynanchum acutum L. subsp. sibiricum (Willd.) Rech. f. was extracted with hexane, acetone, methanol and water individually. A sample was heated in water then extracted with ethyl acetate. Among the extracts, the ethyl acetate extract exhibited the most antiproliferative activity, so isolation of bioactive compounds was carried out from this extract. A new compound, kaempferol-3-O-β-xylopyranosyl-(1-2)-β-rhamnopyranoside (1) along with five known compounds, quercetin-3-O-β-xyloside (2), kaempferol-3-O-β-glucoside (3), quercetin-3-O-β-glucoside (4), kaempferol-3-O-β-rhamnopyranoside (5), and kaempferol-3-O-β-d-neohesperidoside (6) were isolated from ethyl acetate extract. The structures were elucidated by spectroscopic techniques, basically 1D NMR, 2D NMR and LC-TOF/MS. Antiproliferative effects of isolated compounds were determined by xCELLigence using the HeLa (human uterus carcinoma) cell lines. Compound 2 and compound 5 revealed the good antiproliferative activity against HeLa cell lines.

Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing \u2013 a case report

BackgroundEndometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations.Case PresentationIn the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission.A total of 409 genes from the Ampliseq Comprehensive Cancer Panel (Ion Torrent, Thermo Fisher) were analysed by next generation sequencing and mutations in 10 genes, including ARID1A, CTNNB1, PIK3CA and PTEN were identified and confirmed by Sanger sequencing. Primary endometrial as well as ovarian cancer showed an identical mutational profile, suggesting the presence of an ovarian metastasis of the endometrial cancer, rather than a simultaneous endometrial and ovarian cancer. The metachronous lung metastasis showed a different mutational profile compared to the primary cancer. Immunohistochemical staining of the corresponding proteins suggested that the tumour development was driven by alterations in the protein function rather than by changes of the protein abundance in the cell.ConclusionsOur results have demonstrated next generation sequencing as a valuable tool in the differentiation of synchronous primary tumours and metastases, which has an important impact on the clinical decision making process. Similar to breast cancer, targeted therapies based on mutational tumour profiling will become increasingly important in endometrial and ovarian cancer. In summary, our results support the usage of next generation sequencing as a supplementary diagnostic tool, assisting in personalized precision medicine.

The Wertheim hysterectomy: Development, modifications, and impact in the present day

Ernst Wertheim was a pioneer in the history of the surgical treatment of cervical cancer. His English-language manuscript “The extended abdominal operation for carcinoma uteri (based on 500 operative cases),” which was published in 1912, detailed his standardization of the radical hysterectomy and formed the basis of the current treatment for early stage cervical cancer. We contextualize the Wertheim hysterectomy, emphasizing medical advances that allowed for its development and subsequent modification. We then discuss modifications to the originally proposed procedure, including a maximally extended parametrical resection pioneered by Takayama, and the addition of the Taussig en bloc lymph node dissection by Meigs, both of which afforded an improved mortality profile due to decreased disease recurrence. Finally, we discuss progress that has been made in the present day, such as the development of nerve-sparing and fertility-sparing surgeries, as well as the introduction of the robotic platform. In this way, we hope to provide a historical background for the Wertheim hysterectomy—a cornerstone of gynecologic oncology.

Neoadjuvant combined chemotherapy for locally advanced carcinoma of the cervix uteri

Neoadjuvant combined chemotherapy for locally advanced carcinoma of the cervix uteri

Synthesis and in vitro anticancer evaluation of 1,4-phenylene-bis-pyrimidine-2-amine derivatives

A series of 1,4-phenylene-bis-chalcones 3a-3h were synthesized by the reaction of terephthalaldehyde with substituted arylketones in this study. The novel 1,4-phenylene-bis-pyrimidine-2-amine derivatives 5a-5h were obtained by the addition of guanidine hydrochloride to 1,4-phenylene-bis-chalcone 3a-3h in ethanolic KOH under reflux conditions. The structure of the compounds was explained by means of IR, $^{1}$H NMR, $^{13}$C NMR, and elemental analyses. The anticancer activities of 3a-3h and 5a-5h were investigated against rat brain tumor cells and human uterus carcinoma in vitro$.$ Activity tests were performed as dose-dependent assays at eight concentrations. The positive control was 5-fluorouracil (5-FU). Compounds 3c and 3d were examined and they showed high activities as compared to 5-FU against C6 (rat brain tumor) and HeLa (human uterus carcinoma) cells. The anticancer activity of 5h was better than that of 5-FU at high concentrations cell-selectively against C6 cells.

Synthesis and anticancer and cytotoxic effects of novel 1,4-phenylene-bis-N-thiocarbamoylpyrazole and 1,4-phenylene-bis-pyrazolylthiazole derivatives

Thiazolylpyrazoline derivatives were recently reported as potent anticancer agents. In this study, novel 1,4-phenylene-bis-N-thiocarbamoylpyrazoles (3a-h and 1,4-phenylene-bis-pyrazolylthiazoles (5a-h were prepared and screened for their anticancer activities against C6 (rat brain tumor cells) and HeLa (human uterus carcinoma). Anticancer activity studies were performed as a dose-dependent assay starting with eight concentrations. 5-Fluorouracil (5-FU) was used as a positive control. Compounds 3c, 3d, and 3h were examined and they revealed almost the same activities compared with 5-FU in terms of cell selectivity against C6 cells. Moreover, compounds 3a-h had lower cytotoxicity than 5-FU. The low cytotoxicity values of 3a-h as well as their high antiproliferative activity were encouraging, but further studies are required on the use of these molecules as anticancer drugs.

Original Article. Prevalence of HPV16 IgG Antibody and Rt-Pcr DNAdetection in Patients with Laryngeal Carcinoma and Cervical Dysplasia

SummaryHuman papillomaviruses (HPVs) are associated with the most common sexually transmitted infections. It is well documented that high-risk (HR)-HPVtypes are etiologically associated with some cancers. The aim of the study was to investigate HPV16-DNApositivity and prevalence of Ig Gantibody against HPV16 in patients with laryngeal carcinoma and precancerous lesions of cervix uteri in Pleven region, Bulgaria. Material/Methods: We performedacross-sectional study and investigated clinical materials. Attached is real-time PCR-analysis for detection of HPV16-DNA. HPVspecific antibody response by enzyme-linked immunosorbent assay (ELISA) test for detection and quantification of specific Ig Gantibodies in serum were used. Results: For the six-month period, 30 samples were collected and tested. Fourteen of them were found in patients with carcinoma of the larynx and sixteen - in patients with various lesions of cervix uteri.We found that six patients (42.8%) in the first group and eight patients (50%) in the second group were HPV16-DNA-positive. Different age groups were affected. The sera analyzed in this study showed that seven patients (50%) with carcinoma of the larynx were seropositive of whom four (57%) were males. Fourteen of the females with dysplasia (88%) were seropositive. Matching DNApositivity and antibody response were found in 29%of the patients with laryngeal cancer. The match was found in 50%of the females with cervical dysplasia. Conclusions: Real-time PCRisarapid, cost-effective method for detection of HPVs.Ahigh level of seropositivity was found in the two groups of patients.

Synthesis, structural characterization, and antiproliferative/cytotoxic effects of a novel modified poly(maleic anhydride-co-vinyl acetate)/doxorubicin conjugate

Drug carrier, poly(maleic anhydride-co-vinyl acetate) (MAVA or poly[MA-co-VA]) copolymer, was traditionally synthesized by free radical chain polymerization reaction, in methyl ethyl ketone (MEK) organic media at 80 °C, using benzoyl peroxide (BPO) as the radicalic initiator. The purified copolymer was then modified with a chemotherapeutic agent, doxorubicin hydrochloride (DOX) at 75 °C for 72 h, using N-(3-dimethyl-aminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) as the carboxylic acid-activating agent. Structural characterization of the MAVA and the modified MAVA/DOX conjugate was carried out by Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H-NMR and 13C-NMR). Their molecular weights were determined by size-exclusion chromatography (SEC). The spectroscopic and SEC results confirmed that conjugated/modification reaction was successfully carried out. UV spectrophotometric measurements indicated that MAVA/DOX preserved its molecular stability in physiological body fluid, PBS (physiological pH 7.40 at 37 °C). Antiproliferative activities of MAVA/DOX were determined by BrdU cell proliferation ELISA assay using C6 (Rat Brain tumor cells) and HeLa (human uterus carcinoma) cell lines in vitro by comparing with free DOX agent (reference compound). Although MAVA showed low antiproliferative activity, both MAVA/DOX and DOX exhibited greater activity against HeLa and C6. Lactate dehydrogenase (LDH) leakage assay was performed for MAVA/DOX and DOX, which detected a non-toxic effect against C6 even at the highest dose (100 μg/mL). IC50 and IC75 values were also determined using ED50 plus v1.0. Molecular modeling at M06-L/6-31 + G(d,p)//AM1 level showed that the electron density in MAVA/DOX is more localized resulting a higher polarization and thereby a higher dipole moment which shed light on the solubility of MAVA/DOX conjugate.