Prevalence and clonality of synchronous primary carcinomas in the bladder and prostate

Incidental prostate adenocarcinoma (IPCa) has been frequently discovered during postoperative histopathological evaluation of radical cystoprostatectomy specimens in patients with bladder cancer (BCa). However, there is currently no conclusive study addressing the clinical significance of IPCa and the clonal relatedness of IPCa and BCa. Here, we performed a retrospective single‐center review of 919 BCa cases and an additional meta‐analysis including a total of 19 868 individuals who underwent radical cystectomy for bladder cancer. IPCa, mostly clinically insignificant, was detected in 67 of 919 BCa patients (7.3%) and was significantly associated with greater age. In the meta‐analysis, a lower prevalence was observed in Asian than in non‐Asian countries (19% versus 32%), presumably due to their different rates of prostate cancer occurrence. Whole‐exome sequencing on matched BCa and IPCa samples unambiguously revealed independent clonal origins of the synchronous tumors. BCa and IPCa lesions from each patient displayed distinctive genomic abnormalities and largely unrelated mutational signatures of single nucleotide variations, indicating disparate mutational processes underlying bladder and prostate oncogenesis. These findings provide important insights into the incidental nature of prostate adenocarcinoma in patients with bladder cancer, and suggest that the two concurrent diseases can be managed separately. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Formation of vasculogenic mimicry in bone metastasis of prostate cancer: Correlation with cell apoptosis and senescence regulation pathways

Vasculogenic mimicry (VM) has been found in prostate cancer (PCa) as an independent marker of poor prognosis. To investigate the correlation between VM and bone metastasis in PCa, a total of 80 cases were analyzed by CD31 and PAS dual-staining as well as the follow-up data. All cases were divided into two groups: VM-positive and VM-negative (VM-pos/VM-neg). Immunohistochemical staining for investigating the expression of Casepase-3, Bcl-2/Bax, and SA-β-gal was performed. 28 of the 80 PCa cases exhibited VM structure (35.0%). The incidence of bone metastasis in the VM-pos and VM-neg was 67.9% (19/28) and 38.5% (20/52), respectively. The positive rate of Casepase-3 and Bcl-2 expression was significantly different of the two groups (Caspases-3: VM-pos 71.4%, 20/28 vs VM-neg 42.3%, 22/52; Bcl-2: VM-pos 35.7%, 10/28 vs VM-neg 65.4%, 34/52). Bcl-2/Bax ratio of the VM-pos (0.71 ± 0.22) was lower than that of the VM-pos (0.89 ± 0.13). In addition, a higher frequency of SA-β-gal was detected in VM-pos (64.29 ± 86.42) than in VM-neg (25.37 ± 72.21). Taken together, our findings demonstrate that PCa with VM has the tendency to develop bone metastasis. Activations of cell apoptosis and senescence regulation pathways may play important roles in the formation process of VM structure.     

Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.     

Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells

The current investigation aimed to develop a biomimetic, three-dimensional (3D) culture system for poorly adherent bone metastatic prostate cancer cells (C4-2B) for use as an in vitro platform for anti-cancer drug screening. To this end, hyaluronic acid (HA) derivatives carrying complementary aldehyde (HAALD) and hydrazide (HAADH) groups were synthesized and characterized. In situ encapsulation of C4-2B cells was achieved by simple mixing of HAALD and HAADH in the presence of the cells. Unlike two-dimensional (2D) monolayer culture in which cells adopt an atypical spread morphology, cells residing in the HA matrix formed distinct clustered structures which grew and merged, reminiscent of real tumors. Anti-cancer drugs added to the media surrounding the cell/gel construct diffused into the gel and killed the embedded cells. The HA hydrogel system was used successfully to test the efficacy of anti-cancer drugs including camptothecin, docetaxel, and rapamycin, alone and in combination, including specificity, dose and time responses. Responses of cells to anti-neoplastics differed between the 3D HA hydrogel and 2D monolayer systems. We suggest that the data obtained from 3D HA systems is superior to that from conventional 2D monolayers as the 3D system better reflects the bone metastatic microenvironment of the cancer cells.     

紫檀芪对前列腺癌骨转移PC-3细胞活力、凋亡及能量代谢的影响

目的:探讨紫檀芪对人前列腺癌骨转移PC-3细胞活力、凋亡及能量代谢的影响.方法:采用CCK-8法检测紫檀芪对PC-3细胞活力的半数抑制浓度(IC50)和时间依赖性.采用流式细胞术测定紫檀芪对PC-3细胞周期及凋亡的影响.采用分光光度法测定紫檀芪对PC-3细胞能量代谢的影响.采用Western blot法检测相关凋亡蛋白...     

412例前列腺癌患者血清前列腺特异抗原游离与总量比值及骨转移的分析

目的分析前列腺癌(Pca)患者血清前列腺特异抗原游离(FPSA)与总(TPSA)比值(F/T)的结果及骨转移的特点。方法对412例Pca患者术前血清TPSA、FPSA含量和F/T比值及99mTC-MDPECT全身骨骼显像分为二组进行分析。结果无骨转移组为25.5%(105/412例);有骨转移组为74.5%(307/412)。307例Pca骨转移组患者,共有2907个转移病灶,97.5%(2834/2907)显示为"热区"病灶,2.5%显示为"冷区"病灶(73/2907)。有Pca骨转移组血清TPSA、FPSA和F/T分别是97.9±59.4μg/L,10.2±8.1μg/L和0.09±0.04;无ca骨转移组29.6%(16/54),分别是24.8±23.0μg/L,4.4±3.4μg/L和0.12±0.05;二组有显著性差异(P0.01)。TPSA与骨转移程度呈负相关(r=-0.487,P0.05)。当PSA10μg/L,骨转移率为2.6%;当PSA 10～20μg/L,为10.5%;PSA 21～50μg/L,为52.6%;PSA 51～100μg/L,为92.7%;PSA100μg/L,为100%。F/T比值与骨转移程度呈负相关(r=-0.641,P0.05)。F/T0.15者,有84%的Pca患者有骨转移;F/T0.10者,100%的患者有骨转移。结论血清F/T比值小于0.15者,必要时行ECT全身骨骼显像。骨转移的好发部位依次是盆骨、椎骨和肋骨。     

Base excision repair pathway genes polymorphism in prostate and bladder cancer risk in North Indian population

Purpose

Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers.

Methods

This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C > T), 9 (G > A), 10 (G > A), OGG1 Exon 7 (C > G) and APE1 Exon 5 (T > G) genes polymorphism using PCR-RFLP and ARMS.

Results

GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p = 0.001; p = 0.006). Similarly variant containing genotype revealed association with PCa (p = 0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR = 0.25; p = 0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p = 0.028).

Conclusions

Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.     

Hypoxia increases VEGF-A production by prostate cancer and bone marrow stromal cells and initiates paracrine activation of bone marrow endothelial cells

Hypoxia develops at sites of rapid cancer growth near sites of poorly organized vasculature. Heparin binding growth factors (HBGFs) support neoangiogenesis of tumors. We examined the effect of culturing bone-targeted, metastatic C4-2B prostate cancer cells and bone stromal derived HS27a cells under hypoxic conditions on expression of vascular endothelial growth factor (VEGF) family members. A sealed chamber infused with 1% (hypoxic) or 20% (normoxic) O(2) was used. Both cell lines produced VEGF-A in normoxia, but little or no HB-EGF, another HBGF. HS27a cells produced low levels of FGF-2 and HGF, but little or none was secreted by C4-2B cells. Levels of VEGF-A in conditioned medium (CM) from both cell lines doubled when cultured in hypoxia. Similar changes in VEGF-A mRNA levels were seen. Receptor expression was unchanged by hypoxia. Changes in VEGF-A expression during hypoxia were preceded by nuclear accumulation of hypoxia inducible factor-1alpha (HIF-1alpha). Bone marrow endothelial (BME) cells express high levels of VEGFR2/flk-1, and are targets of VEGF-A induced neovascularization. BME cells proliferated in response to treatment with HS27a CM, but not C4-2B CM. BME cells formed tube-like angiogenic structures on growth factor reduced Matrigel in response to CM from HS27a or C4-2B cells. This response was greater when CM was produced under hypoxia, and was reduced by VEGF-A or FGF-2 neutralizing antibodies. We conclude that hypoxia triggers a physiologically relevant increase in VEGF-A by prostate cancer and bone marrow stromal cells which involves a paracrine loop that recruits and activates BME to support tumor neovascularization-related processes.     

Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases

In order to investigate genetic alterations specific to liver metastases of colorectal carcinomas, losses of heterozygosity and replication errors have been compared in 15 cases of primary colorectal carcinoma and in the corresponding metastatic liver tumours. Fifteen microsatellite markers located on 13 different chromosomal arms were used in the study. The LOH patterns of the primary and the metastatic tumours were identical in eight cases and showed differences in seven cases. Areas of deletion predominantly or completely common to the colorectal and the metastatic tumour were detected on chromosomes 5q, 8p, 17p, 18q, and 22q. Preferential loss in metastatic tumours was observed on chromosomal arm 3p. Replication errors were found in four primary tumours and in three of the corresponding secondaries. A replication error phenotype specific to a metastasis was not observed. Copyright © 1999 John Wiley & Sons, Ltd.     

Elevated microsatellite alterations at selected tetranucleotides (EMAST) and mismatch repair gene expression in prostate cancer

Elevated microsatellite alterations at selected tetranucleotides (EMAST), a new form of microsatellite instability (MSI) affecting tetranucleotide repeats, was recently described to be frequent in several tumor types (e.g., bladder, lung, ovarian, and skin cancers). EMAST was found as a form of microsatellite alteration distinct from the MSI phenotype in hereditary nonpolyposis colorectal cancer (HNPCC)-related tumors which mostly affects mono- and dinucleotide repeats. To date, no study has investigated the role of EMAST in prostate cancer. We therefore analyzed 81 prostate tumors using 10 markers frequently detecting EMAST in other cancer types and the National Cancer Institute-consensus panel for HNPCC detection plus BAT40. In addition, we investigated p53 gene alterations [loss of heterozygosity (LOH)] and the expression of p53 and the mismatch repair (MMR) genes hMLH1 and hMSH2 on tissue microarrays. EMAST was detected in 4/81 (5%) cases and MSI in 6/79 (7.6%) cases. LOH of p53 was found in 9/45 (20%) informative cases. There was no correlation between MSI status and the histopathological or molecular characteristics of the tumors. Immunohistochemistry revealed p53 positivity in 5/61 (8%) tumors. There was a significant correlation between tumors showing a recurrence within 3 years after treatment and p53 positivity (p=0.029). Reduced hMLH1 expression, but no complete loss, was detected in 9/41 (22%) tumors without any correlations to histopathological or clinical features. Analysis of hMSH2 expression was available from 58/81 (72%) tumors. Staining intensity was as follows: negative in 7/58 (12%), weak staining in 16/58 (27.5%) samples, moderate staining in 19/58 (33%) samples, and strong staining in 16/58 (27.5%) samples. When negative/weak staining and moderate/strong staining were considered as two groups, there was a significant association between hMSH2 expression and tumor recurrence (p=0.039). In conclusion, our data show that MSI and EMAST are infrequent but distinct patterns of MSI in prostate tumors not related to MMR defects, p53 alterations, and histopathological characteristics. p53 positivity and moderate to strong hMSH2 expression of prostate tumors are correlated with early disease recurrence and indicate an unfavorable clinical course of the disease. These two genes could be useful biomarkers for the prediction of patients’ outcome and should be analyzed in prospective studies. Grant support: This study was supported by a grant from the University of Regensburg to Maximilian Burger (Regensburger Forschungsfoerderung in der Medizin: ReForM A).     

PET/CT对小动物前列腺癌骨转移的观察研究

目的　探讨小动物PET/CT扫描在小鼠前列腺癌骨转移检测中的可行性。 方法　裸鼠23只,随机分为对照组2只,前列腺原位注射组、左心室注射组、胫骨腔内注射组每组各7只。分别采用前列腺原位注射、左心室内注射、胫骨腔内注射的方法建立前列腺癌骨转移动物模型。建模成功后饲养40天,原位注射及左心室注射组采用PET/CT扫描检测,胫骨腔注射组采用小动物高分辨率CT检测,对可疑的骨转移灶行解剖学观察及HE染色明确。 结果　前列腺原位注射组肿瘤细胞聚集腹腔软组织内生长,均未发现明显骨质破坏（0/7）;左心室注射组均发生皮下等软组织转移（7/7）, PET/CT检测出一例胫骨上端骨质破坏,组织学检测证实为骨转移灶(1/7);胫骨腔注射组所有动物均形成明显骨质破坏（7/7）且高分辨率CT检测见骨破坏分级良好。 结论　小动物PET/CT扫描能够良好的显示转移灶在小鼠体内的定位,且能良好的显示骨破坏情况,因此该技术在检测小动物骨转移上有着良好的可行性。     

磷酸甘油酸激酶1和前列腺癌临床特征的相关性及在预后预测中的作用

目的:探讨磷酸甘油酸激酶1在前列腺癌中的表达水平,并分析其与前列腺癌临床特征的相关性以及在预后预测中的作用。方法:收集2013年1月~2014年12月于南方医科大学中西医结合医院住院部行手术治疗的30例良性前列腺增生患者和132例前列腺癌患者标本,用Western blot和免疫组化法分析磷酸甘油酸激酶1在前列腺细胞以及标本中的蛋白表达,并分析磷酸甘油酸激酶1的表达水平与前列腺癌临床特征的相关性以及对前列腺癌预后预测的作用。结果:磷酸甘油酸激酶1在前列腺癌组织和细胞中的表达明显上升,且其表达水平与前列腺癌的Gleason评分、TNM分期、局部浸润、骨转移和血清前列腺特异性抗原(PSA)水平具有显著相关性;Cox分析表明骨转移、血清PSA和PGK1表达是影响前列腺癌患者生存的独立危险因素。生存曲线分析表明高表达的PGK1与前列腺癌的预后不良明显相关。结论:磷酸甘油酸激酶1是影响前列腺癌患者生存的独立危险因素,并能够作为前列腺癌的预后预测标志物。     

Prognostic significance of the presence of intraductal carcinoma of the prostate and bone metastasis in needle biopsy for prostate carcinoma patients with Grade Group 5

Intraductal carcinoma of the prostate (IDC-P) and bone metastasis have been both identified to associate with unfavorable clinical outcome of the prostate carcinoma (PCa). Our objective is to examine whether IDC-P or bone metastasis at diagnostic biopsies was associated with each other and whether they were linked with overall survival (OS) and cancer specific survival (CSS) of Grade Group 5 patients. We retrospectively selected the prostate biopsy specimens of 120 PCa patients with Grade Group 5 from Qilu Hospital of Shandong University between 2012 and 2016. There were 12 patients with IDC-P only, 52 patients with bone metastasis only and 10 patients with both IDC-P and bone metastasis. Overall, there was a significant correlation between the presences of the IDC-P and bone metastasis (P = 0.003). Kaplan-Meier survival analysis demonstrated that the presence of IDC-P and bone metastasis in diagnostic needle biopsy both conferred unfavorable CSS of Grade Group 5 patients. In addition, the presence of bone metastasis was a poor predictor of OS. Univariate and multivariate analysis revealed that bone metastasis was an independent prognostic factor for OS of Grade Group 5 patients, but IDC-P failed to be significant for either OS or CSS. Collectively, our study suggested that bone metastasis is an important prognostic factor and superior than the presence of the IDC-P for PCa patients with Grade Group 5.     

Reduction of insulin signalling pathway IRS-1/IRS-2/AKT/mTOR and decrease of epithelial cell proliferation in the prostate of glucocorticoid-treated rats

Previous studies by our research group using a model of insulin resistance induced by dexamethasone (DEX) showed that in the rat ventral prostate there was epithelial and smooth muscle cell atrophy and there were also alterations in fibroblasts. Proteins of the insulin signalling pathway are known to be very important for cell proliferation and development. Thus, we investigated the insulin signalling pathway and epithelial proliferation in the rat ventral prostate in this model and correlated the findings with expression of glucocorticoid (GR) and androgen (AR) receptors. Insulin resistance was induced in adult male Wistar rats by injection of DEX (1 mg/kg, ip for 5 consecutive days), whereas control (CTL) rats received saline. DEX treatment resulted in a significant decrease in body weight, but not in prostate weight. Reductions in insulin receptor 1 (IRS-1) (CTL 1.11 ± 0.06; DEX 0.85 ± 0.03), IRS-2 (CTL 0.95 ± 0.05; DEX 0.49 ± 0.04), AKT (CTL 0.98 ± 0.03; DEX 0.78 ± 0.02), mammalian target of rapamycin (mTOR; CTL 0.65 ± 0.08; DEX 0.22 ± 0.05), GR (CTL 1.30 ± 0.09; DEX 0.57 ± 0.10) and AR (CTL 1.83 ± 0.16; DEX 0.55 ± 0.08) protein levels were observed in the prostate of DEX-treated rats. The expression of the IRα-subunit, phosphoinositide 3-kinase, p-AKT, p70(S6K) , extracellular signal-regulated kinase (ERK) and p-ERK was not altered. The frequency of AR-positive cells in the epithelium of the prostate decreased in the glucocorticoid-treated group, and the intensity of the reaction for this receptor in the cell nuclei was lower in this group. Furthermore, the treatment with DEX reduced the frequency of proliferating cell nuclear antigen-positive (PCNA) cells 30-fold. This study suggests that the reduction in the insulin signalling pathway proteins IRS-1/IRS-2/AKT/mTOR in the prostate of DEX-treated rats may be associated with the morphological alterations observed previously.     

Keratin profiles in normal/hyperplastic prostates and prostate carcinoma

Summary Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34 E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35H11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/ hyperplastic prostates, RPN1162, 35H11, CK5 and M20 stained luminal cells without staining basal cells, and 34E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35H11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34E12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.     

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Recent studies have highlighted that Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM−) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM− patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM− patients (BC: AUC = 0.71 ± 0.09, P = 0.03; PC: AUC = 0.73 ± 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease.     

Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas

E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and alpha-, beta-, and gamma-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and alpha-, beta-, and gamma-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and alpha-, beta-, and gamma-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and alpha-, beta-, and gamma-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.