Pegylated liposomal doxorubicin in partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer: a prospective study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. METHODS: Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. RESULTS: Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. CONCLUSION: PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.

[Ultrasonographic and clinical features of common testicular germ cell tumors in children].

OBJECTIVE: To study the ultrasonographic manifestations and clinical features of common pediatric testicular germ cell tumors (TGCT) in children. METHODS: We retrospectively analyzed the laboratory, ultrasonographic and clinical data on 92 children with TGCT diagnosed in Shanghai Children's Hospital from March 2013 to January 2019, and investigated the values of the serum alpha-fetoprotein (AFP) level and maximum diameter of tumors in the diagnosis of benign and malignant tumors using the ROC curve. RESULTS: Of the 92 cases of pediatric TGCT, 64 (69.6%) were pathologically confirmed as benign tumors, including 40 cases of teratoma (62.5%), 18 cases of epidermoid cyst (28.1%) and 6 cases of dermoid cyst (9.4%), and the other 28 (30.4%) as malignant neoplasms, including 26 cases of yolk sac tumor (YST, 92.9%) and 2 cases of mixed germ cell tumor (MGCT, 7.1%). Ultrasonography showed that 62.5% of the teratomas were cystic-solid mixed (25/40) and 32.5% solid masses (12/40), that 33.3% of the epidermoid cysts exhibited a typical sign of "onion ring" (6/18) and 22.2% that of capsular calcification (4/18), and that 42.3% of the YSTs displayed isoechoic (11/26), 30.9% hypoechoic (8/26) solid masses without calcium and 26.9% cystic anechoic lesions (7/26). Color Doppler blood flow imaging manifested abundant blood flow signals in most of the YSTs (25/26, 96.2%) but none in either the epidermoid or the dermoid cysts. The area under the ROC curve (AUC) of the serum AFP value was 0.985, with an optimal cutoff value of 124.2 ng/ml, and the sensitivity and specificity of AFP in the diagnosis of benign and malignant tumors were 92.9% and 93.7%, respectively. The AUC of the maximum diameter of the tumors was 0.796, with an optimal cutoff value of 2.7 cm, and the sensitivity and specificity of the maximum diameter of the tumors in the diagnosis of benign and malignant neoplasms were 57.1% and 93.7%, respectively. CONCLUSIONS: Ultrasonographic images have different characteristic manifestations for different pathological types of pediatric TGCT. Pediatric TGCT has a good prognosis and radical orchiectomy should be considered for the treatment of the tumors with serum AFP ≥ 124.2 ng/ml and a diameter ≥ 2.7 cm.

Inflammatory cytokine-induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression.

Microtubule associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in Drosophila. Gwl is an essential kinase for accurate chromosome condensation and mitotic progression, and inhibits protein phosphatase 2A (PP2A), which subsequently dephosphorylates the substrates of cyclin B1-cyclin-dependent kinase 1, leading to mitotic exit. Previous studies have indicated that MASTL has a critical function in the regulation of mitosis in HeLa and U2OS cell lines, though there is currently limited evidence for the involvement of MASTL in hepatocarcinogenesis. The results of the present study revealed that MASTL was inducible by the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), which promoted the proliferation and mitotic entry of human liver cancer cells. It was also determined that MASTL was significantly overexpressed in cancerous liver tissues compared with non-tumor liver tissues. Mechanistically, stimulation by IL-6 and TNF-α induced the trimethylation of histone H3 lysine 4 (H3K4Me3) at the MASTL promoter to facilitate chromatin accessibility. Additionally, H3K4Me3 was associated with the activation of nuclear factor-κB, which subsequently upregulated MASTL expression. These findings suggested that MASTL may have pivotal functions in the development of hepatocarcinoma, and that it may be a potential target for treatment.

Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research.

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.

Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells.

Ovarian cancer is the most lethal type of gynecological cancer and is the fifth leading cause of cancer-associated mortality in females globally. The majority of patients with ovarian cancer suffer from recurrent, progressive disease, due to the acquisition of a resistance phenotype towards various conventional chemotherapy drugs. Although paclitaxel has been demonstrated to be effective against ovarian tumors, there have been reports of the development of a resistant phenotype against Taxol® treatment. The multidrug resistance (MDR)-1/P-glycoprotein has previously been demonstrated to be associated with the acquisition of paclitaxel resistance in certain ovarian tumors. Therefore, the screening of novel drug candidates able to target MDR-1 in ovarian cancer cells and increase the sensitivity to Taxol® is required in order to improve the treatment of this disease. In the present study, the underlying mechanisms by which the dietary flavonoid myricetin enhances the cytotoxic potential of paclitaxel in ovarian cancer cells, was investigated. It was observed that myricetin induced significant cytotoxicity in A2780 and OVCAR3 ovarian cancer cells, with the IC50 value obtained at 25 µM. Myricetin treatment also resulted in the induction of apoptosis in the two cell lines, accompanied by the modulation of certain pro- and anti-apoptotic markers. It was also determined that the pre-incubation of ovarian cancer cells with a lower dose of myricetin was able to increase the cytotoxicity of paclitaxel, due to the significant downregulation of MDR-1 in these cells.

Acoustic Radiation Force Impulse Imaging for Assessing Liver Fibrosis Preoperatively in Infants With Biliary Atresia: Comparison With Liver Fibrosis Biopsy Pathology.

OBJECTIVES: The purpose of this study was to investigate the diagnostic performance of acoustic radiation force impulse (ARFI) in assessing liver fibrosis preoperatively in infants with biliary atresia (BA). METHODS: A total of 50 consecutive infants with BA and 50 healthy infants who underwent ARFI examination were recruited. Siemens Acuson S2000 in Virtual Touch Quantification mode (Siemens Medical Solutions, Mountain View, CA) was used to measure shear wave speeds (SWSs). All infants with BA underwent a liver biopsy within 3 days after ARFI imaging. The liver fibrosis stages of specimens were defined according to the Batts-Ludwig scoring system. The correlation analysis was performed between SWSs and pathological findings. Cut-off values were determined using receiver operating characteristic (ROC) curves. RESULTS: The mean SWS in the BA group was significantly higher than controls (mean ± standard deviation): 1.89 ± 0.45 versus 1.12 ± 0.06 m/s; P < .001). A significant correlation was found between the SWSs and fibrosis stages (r = 0.719, P < .001). The cut-off value for predicting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3), and cirrhosis (F = 4) was 1.53, 1.80 and 2.16 m/s, respectively, and the area under the ROC curve was 0.823, 0.884 and 0.917, respectively. CONCLUSIONS: Acoustic radiation force impulse imaging showed significant correlation with the severity of liver fibrosis by comparing it with liver fibrosis biopsy pathology. It may be an effective method for liver fibrosis assessment, prognosis prediction, and clinical management in infants with BA.

Xiaoaiping combined with cisplatin can inhibit proliferation and invasion and induce cell cycle arrest and apoptosis in human ovarian cancer cell lines.

PURPOSE: The aim of the present study was utilizing Xiaoaiping as a single agent or combined with cisplatin to study its effect on the ovarian cancer cells (HO-8910 and HO-8910PM cells) in tumor cell proliferation, cell apoptosis, cell cycle distribution and cell invasion and migration. METHODS: Both HO-8910 and HO-8910PM cell lines were treated with Xiaoaiping injection, cisplatin or combination. Effects on the cell viability and apoptosis induction were estimated using the Cell counting Kit-8 assay and Annexin V-FITC/Propidium Iodide staining. The distribution of cells in different phases of the cell cycle was assayed using flow cytometry analysis. The effects of Xiaoaiping on the inhibition of cell invasion and migration were researched with Transwell cell migration. RESULTS: Both Xiaoaiping and cisplatin significantly decreased the HO-8910 cell survival versus control arm. Combination treatment showed a higher cytotoxicity to cells in vitro than Xiaoaiping and cisplatin alone. An increase in the G0/G1 phase fraction in HO-8910 cells treated with either Xiaoaiping or cisplatin alone was evident when compared to the fraction in control arm. Compared to the effects of treatment with either agent alone, combination treatment significantly increased the fraction of cells in G0/G1 phase. The HO-8910 cell lines treated with cisplatin demonstrated a significant increase of apoptotic cell rate compared to untreated cell lines. The rate of apoptosis in combined treatment group was significantly higher than that of the single agent treatment groups. A significant reduction in the number of invading cells was observed for Xiaoaiping-treated HO-8910 cells compared with the control group. However, cisplatin did not significantly induce the migration of cells versus untreated cells. Combination of Xiaoaiping and cisplatin significantly suppressed cell invasion and migration versus single-drug treatment in HO-8910 cells. The results of HO-8910PM cells were similar with HO-8910 cells in all tests. CONCLUSIONS: In summary, our results showed that Xiaoaiping as a single agent or combined with cisplatin could induce cell cycle arrest, cause apoptosis and necrosis in ovarian cancer cells, and inhibit cell invasion and migration. The present study also laid a foundation for further investigation involving molecular mechanism. Above all, it may provide a novel therapeutic regimen for ovarian cancer.

Correlation between three-dimensional ultrasound features and pathological prognostic factors in breast cancer.

OBJECTIVES: To investigate the correlation of three-dimensional (3D) ultrasound features with prognostic factors in invasive ductal carcinoma. METHODS: Surgical resection specimens of 85 invasive ductal carcinomas of 85 women who had undergone 3D ultrasound were included. Morphology features and vascularization perfusion on 3D ultrasound were evaluated. Pathologic prognostic factors, including tumour size, histological grade, lymph node status, oestrogen and progesterone receptor status (ER, PR), c-erbB-2 and p53 expression, and microvessel density (MVD) were determined. Correlations of 3D ultrasound features and prognostic factors were analysed. RESULTS: The retraction pattern in the coronal plane had a significant value as an independent predictor of a small tumour size (P = 0.014), a lower histological grade (P = 0.009) and positive ER or PR expression status (P = 0.001, 0.044). The retraction pattern with a hyperechoic ring only existed in low-grade and ER-positive tumours. The presence of the hyperechoic ring strengthened the ability of the retraction pattern to predict a good prognosis of breast cancer. The increased intra-tumour vascularization index (VI, the mean tumour vascularity) reflected a higher histological grade (P = 0.025) and had a positive correlation with MVD (r = 0.530, P = 0.001). CONCLUSIONS: The retraction pattern and histogram indices of VI provided by 3D ultrasound may be useful in predicting prognostic information about breast cancer. KEY POINTS: Three-dimensional ultrasound can potentially provide prognostic evaluation of breast cancer. The retraction pattern and hyperechoic ring in the coronal plane suggest good prognosis. The increased intra-tumour vascularization index reflects a higher histological grade. The intra-tumour vascularization index is positively correlated with microvessel density.

VEGF promotes cardiac stem cells differentiation into vascular endothelial cells via the PI3K/Akt signaling pathway.

Recent research suggested that cardiac stem cells (CSCs) may have the clinical application for cardiac repair. However, their characteristics and the regulatory mechanisms of their growth and differentiation have not been fully investigated. Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. But the homing role of VEGF for CSCs is unclear. In this report, CSCs were isolated, purified, and expanded in vitro from rat heart. VEGF, SU5416 (VEGF receptor blocker), and Wortmannin (PI3K/Akt signaling pathway inhibitor) were used for differentiation into vascular endothelial cells (VECs). Real-time qPCR was selected to confirm the role of PI3K/Akt signaling pathway in VECs differentiation from rat CSCs. The result of real-time qPCR demonstrated that PI3K/Akt signaling pathway plays an important role in rat CSCs differentiated into VECs. So, our research provides a theoretical basis and experimental evidence for therapeutic application of rat CSCs to treat cardiac repair.

[Magnetic resonance staging accuracy for endometrial carcinoma based on different FIGO staging systems].

OBJECTIVE: To evaluate MR accuracy for staging endometrial carcinoma with different FIGO staging systems. METHODS: Between August 2006 and July 2010, 95 women underwent surgery for endometrial carcinoma.In each patient, endometrial carcinoma was staged with magnetic resonance (MR) findings based on the old FIGO staging system and then repeated according to the new FIGO staging system for comparisons.Histopathologic findings were used as a golden standard to compare the sensitivity, specificity, accuracy, positive predictive value and negative predictive value. RESULTS: The accuracy of MRI in the staging of endometrial carcinoma stageI, II and III with the old FIGO staging system were 83.2%, 86.3% and 92.6% versus 88.4%, 96.8% and 91.6% respectively with the new FIGO staging criteria.According the old FIGO staging system, the sensitivity of stage IA, IB and IC were 51.8%, 76.5% and 50.0% and the specificity 85.3% , 55.7% and 95.4% respectively; the sensitivity of stage IIA and IIB were merely 12.5% and 20.0% and the specificity 97.7% and 100.0%.With the new FIGO staging criteria, the above indices were 97.1%, 55.6%, 57.7%, 95.3%, 40.0% and 100.0% respectively. CONCLUSION: With new FIGO staging system versus the old one, the accuracy of MR imaging in the preoperative staging of endometrial carcinoma increases.

Contrast-enhanced transrectal ultrasonography: measurement of prostate cancer tumor size and correlation with radical prostatectomy specimens.

OBJECTIVES: To determine the accuracy of contrast-enhanced transrectal ultrasonography for tumor size measurements of hypoechoic prostate cancer foci located in the peripheral zone. METHODS: A total of 55 men scheduled for radical prostatectomy, with biopsy-proven cancer in hypoechoic foci located in the peripheral zone, were consecutively enrolled in the present prospective study. Each patient underwent grayscale ultrasound and contrast-enhanced transrectal ultrasonography of the prostate according to a standardized protocol. The maximum tumor diameter on grayscale imaging and contrast-enhanced transrectal ultrasonography was compared with that determined using histopathology. RESULTS: A mean underestimation was documented to be approximately 3.9 mm and 0.6 mm for grayscale and contrast-enhanced transrectal ultrasonography imaging, respectively. Grayscale and contrast-enhanced transrectal ultrasonography imaging underestimated measurements by 76.67% (46 of 60) and 48.33% (29 of 60), whereas overestimated measurements were 20% (12 of 60) and 26.67% (16 of 60), respectively. A strong correlation was observed between contrast-enhanced transrectal ultrasonography and histopathological measurements (r = 0.91, P < 0.0001). A weak linear correlation was found between grayscale and histopathological measurements (r = 0.59, P < 0.0001). Bland-Altman analysis results were in complete accordance with correlation analysis results. For cases with maximum histopathological tumor diameters ≤10 mm and >10 mm, 40% (6 of 15) and 86.67% (39 of 45) were index tumors, respectively (P < 0.0001). CONCLUSIONS: Contrast-enhanced transrectal ultrasonography is significantly more accurate than conventional grayscale imaging for measuring prostate tumor size, especially for tumors with a diameter >10 mm, and it might have a role in preoperative assessment of prostatic index tumor sizes.

Utility of the transition zone index for identification of prostate cancer in Chinese men with intermediate PSA levels.

PURPOSE: We aimed to investigate the utility of the transition zone index (TZI) for identification of prostate cancer (PCa) in Chinese men with prostate-specific antigen (PSA) levels of 4-10 ng/mL. METHODS: In this retrospective cohort study, results of transrectal ultrasonography (TRUS)-guided biopsy were assessed in 616 consecutive Chinese men; all subjects had intermediate serum PSA levels and normal digital rectal examination findings. The prostate and transition zone volumes were determined by TRUS. A TZI cutoff value of 0.47 produced the best sensitivity and specificity rates in receiver operating characteristic (ROC) curve analysis and thus was used to classify the study subjects into two subgroups: group 1 with TZI ≤ 0.47 and group 2 with TZI > 0.47. Logistic regression analysis was used to predict outcomes. The variables that were statistically significant in the stepwise logistic regression analysis were assessed using the ROC curve and the area under the curve. RESULTS: Overall, 166 of the 616 patients (26.9%) had histologically confirmed PCa. A total of 238 (38.6%) patients were classified into group 1, of whom 97 (40.8%) exhibited a positive biopsy; and 378 (61.4%) patients were classified into group 2, of whom 69 (18.3%) exhibited a positive biopsy. The stepwise logistic regression analysis revealed that PSA density (PSAD) exhibited the strongest predictive value in the overall population and in group 1, whereas PSA transition zone density (PSATZD) was the optimal predictor in group 2. The ROC curve analysis revealed that when using the TZI-specific 100% sensitivity cutoffs, 17.7% and 25% of the biopsies were unnecessary and could be avoided in the overall patient population prior to and following the division into groups, respectively (P = 0.002). Using an individually generated 95% sensitivity cutoff of 0.12 ng/mL(2) for PSAD and a cutoff of 0.179 ng/mL(2) for PSATZD for TZI-stratified cohorts of TZI ≤ 0.47 and TZI > 0.47, a more consistent specificity of 44% and 46.9%, respectively, for each cohort was observed. CONCLUSIONS: The optimal predictor for PCa differs between various TZI levels. The combination of PSAD in patients with TZI ≤ 0.47 and PSATZD in patients with TZI > 0.47 helps to identify potentially unnecessary biopsies compared to the use of a single PSAD for the entire patient population. The discrepancies regarding an optimal predictor in published reports are most likely due to the differing TZI levels among the cases. In this study, we demonstrated improved identification of PCa using TZI-adjusted cutoffs for PSAD and PSATZD.

[Value of 3D 1H-MRS with body coil at 3T in the differential diagnosis of the prostate cancer].

OBJECTIVE: To assess the value of three dimensional proton magnetic resonance spectroscopy (3D 1H-MRS) with body coil at 3T in the differential diagnosis of prostate cancer. METHODS: Forty patients suspected of prostate cancer underwent MRI and MRS examinations, and then transrectal ultrasound guided prostate biopsy for pathological diagnosis. The MRI and MRS features of benign prostate hyperplasia, prostate cancer and prostatic intraepithelial neoplasia (PIN) were analyzed in comparison with the pathological reports, and the receiver operating characteristic curve was drawn for the diagnosis of cancer from peripheral zones. RESULTS: The examinations were accomplished for all the patients. The mean ratios of (Cho + Cre)/Cit in the interstitial and glandular hyperplasia tissues, the cancer tissue of the central and peripheral glands, the healthy peripheral gland and PIN were 0.75 +/- 0.23, 0.59 +/- 0.14, 1.79 +/- 0.90, 1.18 +/- 0.95, 0.46 +/- 0.18, and 0.97 +/- 0.10, respectively, with statistically significant differences between the cancer and normal prostate tissues (P < 0.01). The optimum threshold for the diagnosis of prostate cancer in the peripheral zone was 0.68 with a sensitivity of 88.6% and a specificity of 88.7%. CONCLUSION: The 3D 1H-MRS with body coil at 3T has a high sensitivity and specificity in the differential diagnosis of prostate cancer, and can provide valuable information for the diagnosis of PIN.

[Splenectomy in epithelial ovarian cancer: analysis of 32 cases].

OBJECTIVE: To investigate the clinicopathologic features, the complications of splenectomy and the survival of epithelial ovarian cancer patients with splenic metastasis. METHODS: A retrospective study was performed of 32 patients with epithelial ovarian cancer who underwent splenectomy for tumor cytoreduction at Zhejiang Cancer Hospital between Jan 1998 and Jun 2006. RESULTS: Of 32 patients, 23 patients (72%) were serous adenocarcinoma and 9 were non-serous adenocarcinoma. According to pathological grade, none was of G1, 11 were of G2, 21 were of G3. Postoperatively, 20 patients were left with no residual tumor, 7 were with < or = 2 cm and 5 were with > 2 cm residual tumor. Postoperative complications developed in 8 patients (25%), including subphrenic abscess, wound infection, gastric perforation, gastrorrhagia, phlebothrombosis, and bowel obstruction. The median follow up was 38 months, estimated 2-year and 5-year overall survival were 70% and 36%. Univariate analysis revealed that histological grade, residual tumor and courses of chemotherapy were influencing factors of the survival (P < 0.05), but multivariate analysis indicated that only residual tumor and courses of chemotherapy independently influenced survival (P < 0.05). CONCLUSIONS: In epithelial ovarian cancer patients with splenic metastasis, low grade serous adenocarcinoma is most common. Splenectomy as part of cytoreductive surgery is associated with modest morbidity and mortality. Residual tumor and courses of chemotherapy are independent factors associated with the prognosis of the patients.