Extracellular Matrix Modulates Outgrowth Dynamics in Ovarian Cancer.

Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood due to the limited availability of cell culture models examining the behavior of cells that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components in human tissues, laminin and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths are developed. It is demonstrated that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53 and various OC cell lines. Outgrowths are initiated by cells that underwent outward translocation and retained the ability to intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography, and small amplitude oscillatory shear experiments reveal that increased ECM levels led to increased fibrous network thickness and high shear elasticity of the microenvironment. These physical characteristics are associated with outgrowth suppression. The low ECM microenvironment mimicks the viscoelasticity of malignant peritoneal fluid (ascites) and supports cell proliferation, cell translocation, and outgrowth formation. These results highlight the importance of the ECM microenvironment in modulating OC growth and can provide additional insights into the mode of dissemination of primary and recurrent ovarian tumors.

MALDI-MSI-A Step Forward in Overcoming the Diagnostic Challenges in Ovarian Tumors.

This study presents the use of matrix-assisted laser desorption and ionization mass spectrometry imaging (MALDI-MSI) directly on the tissue of two ovarian tumors that often present a diagnostic challenge, a low-grade serous borderline ovarian tumor and ovarian fibrothecoma. Different spatial distribution of m/z values within the tissue samples was observed, and regiospecific peaks were identified. Among the 106 peaks in the borderline ovarian tumor five, regiospecific peaks (m/z: 2861.35; 2775.79; 3368.34; 3438.43; 4936.37) were selected using FlexImaging software. Subsequently, the distribution of those selected peaks was visualized on the fibrothecoma tissue section, which demonstrated the differences in the tissue homo-/heterogeneous structure of both tumors. The comparison with the histopathological staining of the ovarian borderline tumor tissue section, obtained during serial sectioning, showed a close correlation of the molecular map with the morphological and histopathological features of the tissue and allowed the identification of different tissue types within the sample. This study highlights the potential significance of MSI in enabling morphological characterization of ovarian tumors as well as correct diagnosis and further prognosis than thus far seen in the literature. Osteopontin, tropomyosin and orosomucoid are only a couple of the molecules investigated using MALDI-MSI in ovarian cancer research. This study, in line with the available literature, proves the potential of MALDI-MSI to overcome the current limitations of classic histopathological examination giving a more in-depth insight into the tissue structure and thus lead to the more accurate differential diagnosis of ovarian tumors, especially in the most challenging cases.

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman.

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T - on admission 1.72 ng/ml and one month later 3.75 ng/ml (normal range 0.08-0.82 ng/ml) and A - 24.90 ng/ml (normal range 0.40-3.40 ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56 × 43 mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges - 0.74 ng/ml (normal range 0.08-0.82 ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.

Serum angiogenesis profile in gestational trophoblastic neoplasm using multiplex immunoassay.

AIMS: Gestational trophoblastic neoplasms (GTN) exemplify a rare, mostly curable but highly aggressive disease. It is often associated with a rapid formation of distant metastases and most likely with an intense neoangiogenesis processes. The aim of the study was to analyze markers in serum of patients with GTN before chemotherapy compared to healthy pregnant women. MAIN METHODS: In this study sixteen protein angiogenesis markers were evaluated in serum of 21 patients with GTN before chemotherapy and compared with healthy pregnant women. Markers were measured using BioPlex Pro Human Cancer Biomarker Panel 1 immunoassay. t-Tests and receiver operating characteristic curves were used for statistical analysis. KEY FINDINGS: Receiver operator curve analysis identified six proteins (sTIE-2, osteopontin, sIL-6α, sVEGFR-2, sEGFR, PECAM-1) which had sufficient sensitivity and specificity (AUC > 0,70) to distinguish GTN patients before the treatment from pregnant controls. The levels of three proteins (sTIE-2, osteopontin and sIL-6α) were altered in GTN patients before the treatment as compared to healthy controls (p = 0,0112; p = 0,0442; p = 0,0488, respectively) and thereby may serve as potential disease markers. SIGNIFICANCE: Serum concentration of proteins related to angiogenesis changes in the course of GTN and may appear useful in the diagnostic process of this disease.

Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy.

Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer-associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first-line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum-based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first-line treatment. Therefore, it is crucial to develop a novel drug that effectively affects ovarian cancer, particularly tumors that are resistant to current chemotherapy. The aim of the present study was to identify genes whose expression may be used to predict survival time or prognosis in ovarian cancer patients treated with chemotherapy. Gene or protein expression is an important issue in chemoresistance and survival prediction in ovarian cancer. In the present study, the research group consisted of patients treated at the Surgical Clinic of the Gynecology and Obstetrics Gynecological Clinical Hospital, Poznan University of Medical Sciences (Poznan, Poland) between May 2006 and November 2014. Additional eligibility criteria were a similar severity (International Federation of Gynecolgy and Obstetrics stage III) at the time of diagnosis, treatment undertaken in accordance with the same schedule, and an extremely good response to treatment or a lack of response to treatment. The performance of the OncoScan® assay was evaluated by running the assay on samples obtained from the four patients and by following the recommended protocol outlined in the OncoScan assay manual. The genomic screening using Affymetrix OncoScan Arrays resulted in the identification of large genomic rearrangements across all cancer tissues. In general, chromosome number changes were detected in all examined tissues. The OncoScan arrays enabled the identification of ~100 common somatic mutations. Chemotherapy response in ovarian cancer is extremely complex and challenging to study. The present study identified specific genetic alterations associated with ovarian cancer, but not with response for treatment.

STUMP - atypowy miesniak macicy - mimikra guza zlosliwego?

This study describes the ultrasound diagnostic process and management in a patient with a unique, rare form of fibroids, i.e. the atypical variant. According to the WHO definition, an atypical uterine myoma cannot be histologically unambiguously diagnosed as benign or malignant. Atypical leiomyomas are characterized by moderate or high quantity of pleomorphic atypical tumor cells, with a small number of mitotic divisions and lack of coagulative necrosis in the tumor. They have a low rate of extrauterine, intraabdominal recurrence, with a negligible risk for distant metastases. Due to the fact the atypical variant of leiomyomas is very rare, it presents a significant diagnostic challenge for obstetricians. The most reliable diagnosis can be made only on the basis of the histopathological examination. In this paper, we present a case of a patient in whom an echo with the diameter of 92 mm and a heterogeneous echogenicity with visible anechoic fields were discovered in the uterine fundus. HD color Doppler demonstrated high vascularization within the tumor, peripherally as well as centrally. The peripheral and central vascularization was rated at 4/4 points on a scale by Exacoustos. The tumor in the uterus met the criteria of high probability of malignancy i.e. 8 points on the vascular scale (power Doppler scale ≥ 7 pts.), solid tumor and a size over 8 cm. Blood flow velocity and vascular resistance in the tumor vessels were evaluated (PSV - 5.76 cm/s, ED - 3.16 cm/s, RI - 0.45 S / D - 1.82). Blood flow in the tumor presented low resistance. Hysterectomy without oophorectomy, with an intraoperative histopathological examination, was performed, and a fibroid was confirmed. The tumor was soft, yellow, with small and medium level of dispersed atypia in microscopic examination. There was no necrosis or mitotic figures. The histopathological image confirmed the atypical leiomyoma of low risk of recurrence. Atypical fibroids are rare in gynecological oncology and they do not have the characteristic clinical course. Furthermore, they do not show the typical characteristics during imaging studies, including ultrasound screening, Sometimes, due to the sonographic image, they should be differentiated from sarcomas. Also, it is necessary to exclude malignancy because of their ambiguous histological characteristics.

Clinical application of HE4 and CA125 in ovarian cancer type I and type II detection and differential diagnosis.

OBJECTIVES: The aim of this study was to assess the sensitivity and specificity of HE4 in detecting and differentiating between types I and II epithelial ovarian cancer (EOC) in comparison with CA125. MATERIAL AND METHODS: We measured HE4 and CA125 serum concentrations in 206 samples taken from patients operated in Gynecologic Oncology Department due to ovarian tumors. Ovarian cancer was confirmed in 89 cases divided into type I and type II. 52 healthy patients without any gynecological disease formed the control group. The sensitivity and specificity for type I and type II EOC detection and differentiating between both types was evaluated for HE4 and CA125. RESULTS: The HE4 and CA125 serum concentrations were significantly higher in type II than in type I EOC (p=0.008696, p=0.000243 respectively). The HE4 and CA125 sensitivity for type I and benign tumors differentiation was 63.16% for both of them and specificity was 87.29% vs 67.89% respectively. For CA125 these differences did not reach statistical significance. The HE4 sensitivity and specificity for type II and benign tumors differentiation were 87.14% and 96.61%, respectively and for CA125 these values were 82.86% and 94.07%, respectively. CONCLUSIONS: Pretreatment analysis of HE4 serum concentration is superior to CA125 in differential diagnosis of ovarian cancer subtypes (I and II). HE4 is superior to CA125 in detecting ovarian cancer type II. Neither HE4 nor CA125 is an effective diagnostic tool for type I ovarian cancer detection. A new highly specific and highly sensitive tumor marker for type I EOC is needed.

MT477 acts in tumor cells as an AURKA inhibitor and strongly induces NRF-2 signaling.

BACKGROUND: The novel compound thiopyrano [2,3-c]quinoline (MT477) has been shown to exhibit antitumor activity in both in vitro and in vivo studies. The present study examined the expression levels of 10,000 genes and how they changed after MT477 treatment in three cancer cell lines: H226, MDA231 and MiaPaCa-2. Materials and Methods/ RESULTS: Molecular function analysis revealed changes in genes involved in cell death, cell-cycle progression and cellular growth and proliferation in all three cancer cell lines. Canonical pathway analysis showed the involvement of the NRF2-mediated oxidative stress response, glucocorticoid, p53, RXR-VDR, G(1)/S checkpoint regulation, ERK, SAPK/JNK and JAS/Stat signaling. Analysis of 234 kinases and phosphatases using a kinase inhibition assay demonstrated a strong inhibitory effect for MAPK14 (104 ± 2%), AMPK A2/B1/G1 (89%) and FGR (83 ± 2%). AURKA was inhibited at 77 ± 1%. MiaPaCa-2 tumor xenograft studies showed a 49.5 ±1 4.8% inhibitory effect in mice treated with 100 µg/kg MT477 compared to untreated mice (p=0.0021). CONCLUSION: MT477 induces molecular mechanisms related to cell death, survival, and inhibition of cellular growth in vitro and in vivo.

PKC-alpha inhibitor MT477 slows tumor growth with minimal toxicity in in vivo model of non-Ras-mutated cancer via induction of apoptosis.

MT477 is a novel thiopyrano[2,3-c]quinoline with anti-cancer activity. The purpose of the present study was to evaluate different doses and treatment schedules of MT477 in an in vivo xenograft model of non-Ras-mutated cancer, as well as determine its biological effects and mechanism of action via the four conventional PKC isoforms: α, ßI, ßII, and γ. Here, we show that MT477 inhibits the activity of PKC-α and its downstream targets, ERK1/2 and Akt, before it has an effect on Ras activity. MT477 treatment of cultured H226 cells induced apoptosis and increased focal cell adhesion and formation of actin stress fibers. H226 tumor size in mice continuously treated with intraperitoneal MT477 (1 mg/kg) was 62.1 ± 15.3% smaller than the average tumor size in control mice. Blood serum chemistry revealed minimal toxicity in mice. Taken together, these results support the conclusion that MT477 acts as a direct PKC-α inhibitor in non-Ras mutated cancer, with maximum effectiveness when given in a continuous treatment schedule.

MT103 inhibits tumor growth with minimal toxicity in murine model of lung carcinoma via induction of apoptosis.

Molecular topology (MT) was used to develop quantitative structure-activity relationship (QSAR) models to screen databases for new anticancer compounds. One of the selected compounds was MT103, an isoborneol derivative, with a promising profile predicted to slow tumor growth through pro-apoptotic signaling and protein kinase C inhibition. We found that MT103 inhibited the growth of a wide variety of cancer cell types as verified by the NCI-60 cancer cell line panel. MTT cell viability assay showed that MT103 inhibited 50% of the growth of HOP-92, ACHN, NCI-H226, MCF-7, and A549 cancer cell lines at much lower concentrations than that required for HUVECs and human fibroblasts. MT103 stimulated apoptosis in NCI-H226 lung carcinoma cells as measured by oligonucleosomal DNA fragmentation. However, protein kinase C was not targeted by MT103, as predicted by in silico modeling. MT103 slowed in vivo tumor growth and metastatic spread of NCI-H226 cells injected subcutaneously into NOD/SCID mice, without eliciting any severe adverse events as monitored by animal survival, blood serum analysis, and histological analysis of organs. Oral administration of MT103 nanoparticles (200 nm in diameter), which were generated with ElectroNanospray™ technology, inhibited in vivo growth of HOP-92 lung carcinoma cells almost as effectively as intraperitoneal injections of cisplatin. Taken together, our study of a novel anti-cancer drug identified using a molecular topology-based approach to drug discovery demonstrates that MT103 has anti-tumor activity in vitro and in vivo, although additional studies are needed to elucidate its mechanism of action.

[Laparoscopic gonadectomy for androgen insensitivity syndrome--case report]. / Laparoskopowa gonadektomia u pacjentki z kompletnym zespolem niewrazliwosci na androgeny--opis przypadku.

UNLABELLED: Androgen insensitivity syndrome (AIS, Morris syndrome) is an X-linked recessive disorder of sexual development caused by the mutation of the androgen receptor coding gene (locus Xq11-q12). We present a case of a 17-year-old girl diagnosed because of primary amenorrhea. Her cytogenetic analysis revealed the kariotype of 46, XY. Clinical examinations, based on the Quigley's scale, showed features of complete AIS. Hormonal tests brought the following results: FSH - 2.81 mIU/ml, LH - 13.88 mIU/ml. Testosterone value met the norm for a male individual in reproductive age (7.97 ng/ml). Family anamnesis revealed no episodes of genetic diseases. Due to the risk of neoplasia, the diagnosis was an indication for surgical gonads removal, which was performed laparoscopically. Histopathologic examination showed tubular adenoma with immature seminiferous tubules without spermatogenesis, and serous cysts. Patient was discharged on the next day after the operation in good general condition, and estrogen therapy was prescribed. CONCLUSION: Laparoscopy is an effective method in AIS treatment.

Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor, multiple myeloma, and renal cell carcinoma cell lines.

BACKGROUND: Local recurrence with subsequent osteolysis is a problem after intralesional curettage of giant cell tumor of bone, myeloma, and metastatic carcinoma. The bisphosphonate zoledronic acid (zoledronate) has been shown to reduce osteoclast activity, and its local administration is a potentially attractive therapy, especially for the osteoclast-rich giant cell tumor. The aim of this study was to analyze the elution dynamics of zoledronic acid release from acrylic bone cement and its in vitro antitumor efficacy. METHODS: Various concentrations of zoledronic acid were mixed with bone cement and placed in distilled water. The concentration in the water was measured daily for fourteen days. The cytotoxic effects of the dissolved zoledronic acid on cultures of multiple myeloma, giant cell tumor, and renal cell carcinoma cells were tested with use of the MTT assay (tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye) and analyzed according to the zoledronic acid concentration and the elapsed time. RESULTS: The release of zoledronic acid was greatest during the first twenty-four hours for all concentrations and decreased rapidly during the next forty-eight hours to reach a plateau after four days. The proliferation assay (MTT) showed zoledronic acid to have significant cytotoxicity in cultures of stromal giant cell tumor, multiple myeloma, and renal cell carcinoma cells. In addition, zoledronic acid decreased the number of viable tumor cells in a dose-dependent manner. Renal cell carcinoma from bone (RBM1-IT4) and stromal giant cell tumor of bone were more susceptible to zoledronic acid than was multiple myeloma. CONCLUSIONS: The method presented in our study is a reproducible technique for evaluating zoledronic acid elution from bone cement and determining its impact on tumor growth. Zoledronic acid is released from bone cement, remains biologically active despite the polymerization of cement, and inhibits the in vitro growth of cell lines from giant cell tumor of bone, myeloma, and renal cell carcinoma.

Novel Ras pathway inhibitor induces apoptosis and growth inhibition of K-ras-mutated cancer cells in vitro and in vivo.

MT477 is a novel quinoline with potential activity in Ras-mutated cancers. In this study, MT477 preferentially inhibited the proliferation of K-ras-mutated human pulmonary (A549) and pancreatic (MiaPaCa-2) adenocarcinoma cell lines, compared with a non-Ras-mutated human lung squamous carcinoma cell line (H226) and normal human lung fibroblasts. MT477 treatment induced apoptosis in A549 cells and was associated with caspase-3 activation. MT477 also induced sub-G1 cell-cycle arrest in A549 cells. Although we found that MT477 partially inhibited protein kinase C (PKC), it inhibited Ras directly followed in time by inhibition of 2 Ras downstream molecules, Erk1/2 and Ral. MT477 also caused a reorganization of the actin cytoskeleton and formation of filopodias in A549 cells; this event may lead to decreased migration and invasion of tumor cells. In a xenograft mouse model, A549 tumor growth was inhibited significantly by MT477 at a dose of 1 mg/kg (P < 0.05 vs vehicle control). Taken together, these results support the conclusion that MT477 acts as a direct Ras inhibitor. This quinoline, therefore, could potentially be active in Ras-mutated cancers and could be developed extensively as an anticancer molecule with this in mind.

Addition of receptor tyrosine kinase inhibitor to radiation increases tumour control in an orthotopic murine model of breast cancer metastasis in bone.

The receptor tyrosine kinase inhibitor, SU11248, was added to localised radiation to evaluate the response of bone metastases and to define the basic mechanism of radiosensitisation. Treatment with SU11248 and radiation was assessed in vitro using cultured 4T1 breast cancer cells and in vivo using an orthotopic 4T1 murine mammary tumour model of breast cancer bone metastasis. Cultured 4T1 cells treated with SU11248 (1 microM) and radiation (10 Gy) showed an almost 7.5-fold increase in caspase-mediated apoptosis after 24 h of incubation, compared to either treatment alone. Mice treated with SU11248 (40 mg/kg/daily) and radiation (15 Gy/single-dose) had a relatively greater reduction in tumour growth, bone osteolysis, osteoclast maturation and microvessel density. Combined modality treatment resulted in improvements in behavioural pain assessment scores and normalisation of neurochemical changes in the spinal cord receiving primary afferent innervation from tumour-bearing femora. Our study demonstrates that SU11248 enhances the radiation control of metastatic breast tumours in bone and tumour-induced pain.

Enzastaurin renders MCF-7 breast cancer cells sensitive to radiation through reversal of radiation-induced activation of protein kinase C.

Enzastaurin (LY317615.HCI), a protein kinase C (PKC)-beta inhibitor, has a radiosensitising effect on 4T1 murine breast cancer and human glioma cells; however, the exact mechanism of this action has not been evaluated. The present study investigated the effects of enzastaurin and gamma irradiation on PKC activity in MCF-7 human breast cancer cells in vitro and in vivo. Enzastaurin (5 microM) in combination with irradiation (2-8 Gy) produced a synergistic decline in MCF-7 clonogenic cell survival. Analysis of MCF-7 cells stained with Annexin V and 7-aminoactinomycin D showed a dose-dependent increase in apoptosis in response to enzastaurin (3, 5 and 7 microM) and irradiation (10 Gy) compared to irradiation alone. This pro-apoptotic effect was confirmed by increases in caspase-3 and -9 activity. In a MCF-7 xenograft model, irradiation with 25 Gy increased PKC-alpha activity by 2.5-fold compared to untreated controls, whereas PKC-epsilon and -betaII activity was increased by 1.8-fold. Radiation-induced activation of all three anti-apoptotic isoforms of PKC was reversed by pre-treatment with enzastaurin (75 mg/kg, twice daily for 3 days). We conclude that enzastaurin has a radiosensitising effect on MCF-7 human xenograft tumours through the reversal of anti-apoptotic activation of PKC isoforms.

A novel quinoline, MT477: suppresses cell signaling through Ras molecular pathway, inhibits PKC activity, and demonstrates in vivo anti-tumor activity against human carcinoma cell lines.

MT477 is a novel thiopyrano[2,3-c]quinoline that has been identified using molecular topology screening as a potential anticancer drug with a high activity against protein kinase C (PKC) isoforms. The objective of the present study was to determine the mechanism of action of MT477 and its activity against human cancer cell lines. MT477 interfered with PKC activity as well as phosphorylation of Ras and ERK1/2 in H226 human lung carcinoma cells. It also induced poly-caspase-dependent apoptosis. MT477 had a dose-dependent (0.006 to 0.2 mM) inhibitory effect on cellular proliferation of H226, MCF-7, U87, LNCaP, A431 and A549 cancer cell lines as determined by in vitro proliferation assays. Two murine xenograft models of human A431 and H226 lung carcinoma were used to evaluate tumor response to intraperitoneal administration of MT477 (33 microg/kg, 100 microg/kg, and 1 mg/kg). Tumor growth was inhibited by 24.5% in A431 and 43.67% in H226 xenografts following MT477 treatment, compared to vehicle controls (p < 0.05). In conclusion, our empirical findings are consistent with molecular modeling of MT477's activity against PKC. We also found, however, that its mechanism of action occurs through suppressing Ras signaling, indicating that its effects on apoptosis and tumor growth in vivo may be mediated by Ras as well as PKC. We propose, therefore, that MT477 warrants further development as an anticancer drug.

Protein kinase C-beta inhibitor enzastaurin (LY317615.HCI) enhances radiation control of murine breast cancer in an orthotopic model of bone metastasis.

Radiation therapy is a widely used treatment for metastatic bone cancer, but the rapid onset of tumor radioresistance is a major problem. We investigated the radiosensitizing effect of enzastaurin, a protein kinase Cbeta (PKCbeta) inhibitor, on bone tumor growth and tumor-related pain. We found that enzastaurin enhanced the effect of ionizing radiation on cultured murine 4T1 breast cancer and murine endothelial cells, suppressing their proliferation and colony formation. Enzastaurin and ionizing radiation also induced caspase-mediated apoptosis of 4T1 cells to a greater degree than radiation alone. Enzastaurin treatment of 4T1 cells blocked the phosphorylation of PKCbeta, as well as Ras and two of its downstream effectors ERK1/2 and RAL-GTP. Using an orthotopic model of bone metastasis, we observed that a combination of enzastaurin and localized radiation treatment reduced tumor blood vessel density, bone destruction and pain compared to single modality treatment. In conclusion, we demonstrate that inhibition of PKCbeta in combination with localized radiation treatment suppresses tumor growth and alleviates pain as compared to radiation-only treatment. We also show that the radiosensitizing effect of enzastaurin is associated with suppression of tumor cell proliferation and tumor-induced angiogenesis possibly through inhibition of the Ras pathway.

[Morphologic pattern of uterine myomas enucleated at cesarean section]. / Obrazy mikroskopowe miesniaków macicy wyluszczonych w czasie ciecia cesarskiego.

OBJECTIVES: Myomectomy is the most common surgery performed at cesarean delivery. This report reviews a 10-year experience with surgical management of leiomyomata at cesarean section. MATERIAL AND METHODS: [corrected] 101 women had myomectomies performed at cesarean delivery during the period studied. (0.89% of all cesarean sections). We reviewed the pathology on the all specimens. RESULTS: In 90 cases only one myoma was enucleated, in other 11 two or more myomas were enucleated. 59 myomas were hypertrophic and 52 myomas were necrotic. CONCLUSIONS: The most frequent secondary change reported was hypertrophy of the muscle fibers and necrosis.