Drug resistance in ovarian cancer: from mechanism to clinical trial.

Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

[Design and analysis of a novel light visible spectrum imaging spectrograph optical system].

A novel visible spectrum imaging spectrograph optical system was proposed based on the negative dispersion, the arbitrary phase modulation characteristics of diffractive optical element and the aberration correction characteristics of freeform optical element. The double agglutination lens was substituted by a hybrid refractive/diffractive lens based on the negative dispersion of diffractive optical element. Two freeform optical elements were used in order to correct some aberration based on the aberration correction characteristics of freeform optical element. An example and frondose design process were presented. When the design parameters were uniform, compared with the traditional system, the novel visible spectrum imaging spectrograph optical system's weight was reduced by 22.9%, the total length was reduced by 26.6%, the maximal diameter was reduced by 30.6%, and the modulation transfer function (MTF) in 1.0 field-of-view was improved by 0.35 with field-of-view improved maximally. The maximal distortion was reduced by 1.6%, the maximal longitudinal aberration was reduced by 56.4%, and the lateral color aberration was reduced by 59. 3%. From these data, we know that the performance of the novel system was advanced quickly and it could be used to put forward a new idea for modern visible spectrum imaging spectrograph optical system design.

[Study and analysis of light infrared detection system with dual spectrum and wide temperature range].

Because harmonic diffractive optics elements has special achromatism, athermalization and arbitrary phase modulation characteristics, an infrared detection system method with dual spectrum and wide temperature range was presented based on the most advanced infrared dual color detector which had a format of 320 X 240 and the pixel pitch of 30 microm. A hybrid refractive/ harmonic diffractive infrared detection system with dual spectrum and wide temperature range was designed. The working wavelength range was 3. 8 - 4. 2 and 8. 8 -11. 2 microm. The system was only consisted of three lenses, including one aspheric surfaces and a harmonic diffraction surface, which made the system have compact structure and light weight. In the temperature range -120 -200 degreesC, the RMS radius of spot diagram in 3. 8 approximately 4. 2 and 8. 8-11. 2 pm was 19. 07 and 17. 75 microm respectively, which is less than the pixel size of infrared detector with 30 m, the enclosed energy in 30 microm, the enclosed energy in 3. 8-4. 2 and 8. 8-11. 2 microm is 88. 7% and 82. 4% in two pixel size. The method and structure was convenient and predominant. It was proved that the design was feasible.

Multifactorial impact on the outcome of interval debulking surgery in patients with advanced epithelial ovarian or peritoneal cancers.

OBJECTIVE: To evaluate the impact of multiple clinical features upon the outcome of interval cytoreductive surgery and thus upon the survival in patients with advanced ovarian cancer and primary peritoneal carcinoma. METHODS: A retrospective analysis of patients receiving NACT followed by IDS between 2009 and 2017. Patients were analyzed according to the pre-NACT CA125, pre-IDS CA125, pre-IDS CA125 decline, patients' pre-IDS BMI, multisite bowel involvement and different working years of surgeons, for their influence upon the IDS outcome (e.g. optimal vs suboptimal) and the survival. RESULTS: After interval debulking surgery following 1-6 cycles of NACT, all patients analyzed were identified as optimal (n = 113) and suboptimal (n = 47) based on patients' record. The PFS/OS were 21/68 months and 9/26 months in optimal and suboptimal groups, respectively (p = .000, p = .000). Although differential levels of pre-IDS CA125, pre-IDS CA125 decline, bowel involvement and surgeons' working years were found to be significantly different between the two groups, surgeons' working years and multisite bowel invasion were the independent factors for IDS outcome, and the latter one was also highly related to survival. CONCLUSIONS: Following NACT, the rate of optimal IDS might be improved for patients without multisite bowel involvement. For those with bowel involvement, management strategy made by well-experienced surgeons might be a key factor for the outcome of IDS.

Serum CA125 levels predict outcome of interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the correlation between the changes of serum CA125 level and the outcome of interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC). METHODS: A retrospective review for 62 patients with FIGO stage III or IV EOC treated with NACT-IDS was conducted. Demographic data, clinical characters, pathological features and prognosis were collected. Continuous variables were evaluated by Student's t-test or Mann-Whitney U test. Categorical variables were evaluated by chi square test or Fisher's exact test as appropriate for category size. Standard univariate analyses and multivariable analysis with logistic regression were performed to identify independent predictor of optimal IDS. Kaplan-Meier method was used to analyze the prognosis. RESULTS: No statistical difference was found on serum CA125 levels between suboptimal (n = 34)IDS and optimal (n = 28) IDS either before NACT (median levels: 1552.2 U/mL and 1715.5 U/mL, p = 0.453) or before IDS (median levels: 27.25 U/mL and 26.4 U/mL, p = 0.713). Those with optimal IDS achieved longer progression free survival (PFS) and overall survival (OS) than those with suboptimal IDS (median PFS: 22 and 13.5 months, p < 0.001; median OS: 33.5 and 21 months, p = 0.005). Eighteen of 31 patients (58.1%) with serum CA125 declines ≥0.95828 achieved optimal IDS compared to 10 of the 31 patients (32.3%) with serum CA125 declines <0.95828 (p = 0.041). Standard univariate analyses and multivariable analysis showed that serum CA125 declines ≥0.95828 could be an independent predictor of optimal IDS. CONCLUSION: Patients who underwent optimal IDS have better prognosis compare to suboptimal IDS. The changes of serum CA125 after neoadjuvant chemotherapy might predict optimal interval debulking surgery in patients with advanced epithelial ovarian cancer.