金黄色葡萄球菌L型和人乳头瘤病毒与宫颈癌关系的研究

应用改良革兰氏染色和免疫组化染色（ＡＢＣ法）,对２７０例宫颈癌和３３例慢性宫颈炎进行了研究。结果发现,宫颈癌革兰氏染色切片中细菌Ｌ型感染率（７５．１％）明显高于慢性宫颈炎（４５．５％）（Ｐ＜０．０５）,金黄色葡萄球菌Ｌ型抗原阳性率（７６．２％）明显高于人乳头瘤病毒（ＨＰＶ）抗原阳性率（５７．１％）。Ｌ型、ＨＰＶ混合感染率为４２．８％。上述结果表明宫颈癌中金葡菌Ｌ型与ＨＰＶ感染均常见,尤其金葡菌Ｌ型感染更为多见;金葡菌Ｌ型与ＨＰＶ感染的致病特征相似,两者均有不同程度的空泡细胞出现。提示金葡菌Ｌ型感染可能也是宫颈癌的致癌重要因素之一。     

SYNTHESIS AND ANTITUMOR ACTIVITY OF 5-BROMO-1-MESYLURACIL

Large-scale preparation of 5-bromo-1-mesyluracil (BMsU) 4 has been optimized. BMsU was synthesized by condensation of silylated 5-bromouracil and MsCl in acetonitrile or by the reaction of 5-bromouracil with MsCl in pyridine. The same product was obtained by bromination of 1-mesyluracil. The purpose of this study was to elucidate the effects of BMsU on the biosynthetic activity of tumor cell enzymes involved in DNA, RNA and protein syntheses, and in de novo and salvage pyrimidine and purine syntheses. Investigations were performed in vitro on human cervix carcinoma cells (HeLa). BMsU displayed inhibitory effects on DNA and RNA syntheses in HeLa cells after 24 h of treatment. De nova biosynthesis of pyrimidine and purine was also affected. Antitumor activity of BMsU is closely associated with its inhibitory activity on the enzymes that play an important role in the metabolism of tumor cells. In vivo antitumor activity of BMsU was also investigated. The model used in investigations was a mouse anaplastic mammary carcinoma transplanted into the thigh of the right leg of CBA mice. Significant reduction in tumor growth time was achieved with BmsU administered at a dose of 50 mg/kg.     

Endogenously Expressed Truncated P2X7 Receptor Lacking the C-Terminus is Preferentially Upregulated in Epithelial Cancer Cells and Fails to Mediate Ligand-Induced Pore Formation and Apoptosis

A truncated naturally occurring variant of the human purinergic receptor P2X7 (P2X7-R) was found in human cancer cervical cells. The novel protein consists of 258 amino acids, and compared to the wild-type P2X7-R it lacks the entire intracellular carboxy terminus, the second transmembrane domain, and the distal third of the extracellular loop. The truncated P2X7-R failed to form pores and mediate apoptosis, and it interacted with the wild-type P2X7-R in a manner suggesting auto-hetero-oligomerization. In contrast to cancer cells the novel truncated P2X7-R was expressed relatively little in normal cervical cells. These data raise the possibility that coexpression of the truncated form could block P2X7 mediated apoptosis and promote uncontrolled growth of cells.     

Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways

Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC₅₀ = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP‐homologous protein as well as apoptosis signal‐regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial‐related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.     

Apport de la TEMP/TDM pour la détection du ganglion sentinelle dans les cancers du col utérin et de l’endomètre

The sentinel lymph node procedure is still under evaluation for the management of cervical and endometrial carcinomas. The aim of our study was to determine the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) for preoperative sentinel lymph node mapping in uterine cancers. Sixty-eight patients with cervical (n = 42) or endometrial carcinoma (n = 26) underwent preoperative lymphoscintigraphy for sentinel node mapping. Sentinel node detection rate with conventional planar imaging was similar to that of SPECT/CT (87.1 versus 91.8 %) in the whole cohort. However, SPECT/CT detected a higher number of sentinel nodes in more than one third of patients, affected by either cervical or endometrial carcinoma. The rate of non or insufficiently contributive procedures (lack of uptake or unilateral uptake) in endometrial carcinomas was 47 % with conventional planar imaging, and 30 % with SPECT/CT. Sensitivity of both procedures for the detection of metastatic nodes was 81.8 %, compared to 100 % for the intraoperative combined detection (gamma probe sonde and blue dye). The impact of SPECT/CT for the sentinel lymph node detection in cervical and endometrial carcinomas needs further evaluation. Nevertheless, SPECT/CT may provide additional information when conventional planar imaging detects only unilateral uptake, may improve identification of atypical localizations, and facilitate surgical approach.     

Coincident increases in oxytocin receptor expression and EMG responsiveness to oxytocin in the ovine cervix at oestrus

This study has localised oxytocin receptor (OTR) mRNA expression within the cervix of non-pregnant ewes and related this to changes in the sensitivity of the cervical musculature to administered oxytocin (OT) during the oestrous cycle by recording electromyographic (EMG) activity. Cervices were collected from 34 ewes at specified time points throughout the cycle. OTR mRNA expression was localised by in situ hybridisation and results were expressed as optical density measurements from autoradiographs in each of four different cervical regions. EMG recordings were made for up to 8 h per day from four non-pregnant ewes undergoing seasonal oestrous cycles between Days −3 and +3 relative to oestrus (Day 0). The highest concentrations of OTR mRNA were detectable within the luminal epithelium (LE) of the cervix, with values increasing from Day 15 of the cycle, peaking during the follicular phase (P<0.001, compared to the mid-luteal phase) and returning to basal by Day 2. There was a small but significant increase in OTR mRNA hybridisation (above basal/luteal phase values) within the stromal cells (STR) adjacent to the lumen (P<0.05) during the same time period, but no differences from basal values were detectable in the dense collagenous annular ring or in tissue superficial to this. Analysis of pooled EMG activity recorded daily from the cervix indicated that endogenous contractile activity was higher on Day 0 than on the Days +1 (P<0.05), −2, +2 and +3 (P<0.001). The response to bolus intravenous (i.v.) injections of 25 mU OT (25 mU) varied with day of the cycle. This dose produced a measurable and significant response on Days 0 (P<0.001) and +1 (P<0.001), but not on any of the other days, indicating that the sensitivity of the cervical musculature to OT peaked on these days. These data show that the cervix is highly responsive to OT at oestrus. This coincides with an increase in OTR mRNA expression in the luminal epithelial cells, suggesting the likely production of an intermediary messenger between the epithelial and smooth muscle cells.     

The effect of estradiol on COX-2, EP2, and EP4 mRNA expression and the extracellular matrix in the cervix of the hypogonadotrophic, ovariectomized ewe

There is a degree of cervical relaxation in the ewe at estrus that is regulated by changes in prostaglandin synthesis, prostaglandin receptor expression, and changes in the cervical extracellular matrix. It is likely that these are regulated by changes in periovulatory hormones, particularly estradiol. This study determined the effect of estradiol benzoate on the mRNA expression of cyclooxygenase-2 (COX-2) and the prostaglandin E receptors EP₂ and EP₄, the concentration of cervical hyaluronan, and the proportion of smooth muscle and collagen in the cervix of the hypogonadotrophic ovariectomized ewe (Ovis aries). Ovariectomized hypogonadotrophic ewes were given 100 μg estradiol benzoate, and their cervices were collected 0, 24, and 48 h thereafter to determine the expression of cervical COX-2, EP₂, and EP₄ mRNA by in situ hybridization, the concentration of hyaluronan by ELISA, and the proportion of smooth muscle and collagen by Masson's trichrome staining. Estradiol benzoate increased the mRNA expression of COX-2 and EP₄ within 24 h after treatment (P < 0.05), whereas EP₂ mRNA, hyaluronan, and the ratio of smooth muscle to collagen did not change within 48 h after treatment. The COX-2, EP₂, and EP₄ mRNA expression were greatest in the smooth muscle layers (P < 0.05) and least in the luminal epithelium (P < 0.05). In conclusion, we inferred that estradiol regulates cervical COX-2 and EP₄ mRNA expression and may regulate cervical relaxation via the synthesis of prostaglandin E₂ and activation of the PGE₂ receptors EP₂ and EP₄.     

Increasing incidence and survival of corpus uteri cancer in Estonia over the past two decades

BackgroundCorpus uteri cancer has become the fourth most common female cancer in Europe. In Estonia, the prevalence of obesity is increasing, and corpus uteri cancer survival has been relatively low. The aim of the study was to evaluate incidence, mortality and survival trends of corpus uteri cancer in Estonia by age, stage and histological subtypes with an emphasis on surgical treatment.MethodsEstonian Cancer Registry data on incident cases of corpus uteri cancer were used to examine incidence trends (1995–2016) and calculate relative survival ratios (RSR) (1996–2016). Cases were classified by morphology and FIGO stage. Causes of Death Registry data were used to analyse corrected mortality (1995–2017).ResultsA total of 4281 cases were diagnosed in 1996–2016. A significant increase was seen in age-standardized incidence from 2009, while mortality remained stable throughout the study period. Significant increases were observed for type I cancers and age groups ≥65 years. Overall age-standardized 5-year RSR improved from 70% in 1996–2002 to 78% in 2010–2016. Survival increased for type I cancers, all age groups and all stages (significantly for stage IV). The proportion of surgically treated cases increased significantly from 85% to 89%, with the largest increases seen in older age groups and later stages.DiscussionThe rising corpus uteri cancer incidence in Estonia is driven by the type I cancer trend. Survival gain for later stages and older age groups likely reflected more frequent surgical treatment. To reduce mortality, further efforts are necessary to ensure appropriate care for all patients.