Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

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The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents.

As the standard treatments for cancer, chemotherapy and radiotherapy have been widely applied to clinical practice worldwide. However, the resistance to cancer therapies is a major challenge in clinics and scientific research, resulting in tumor recurrence and metastasis. The mechanisms of therapy resistance are complicated and result from multiple factors. Among them, non-coding RNAs (ncRNAs), along with their modifiers, have been investigated to play key roles in regulating tumor development and mediating therapy resistance within various cancers, such as hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, etc. In this review, we attempt to elucidate the mechanisms underlying ncRNA/modifier-modulated resistance to chemotherapy and radiotherapy, providing some therapeutic potential points for future cancer treatment.

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Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

Cesarean Scar Pregnancies: A Systematic Review of Treatment Options.

Purpose of reviewIntrauterine adhesions, also known as Asherman's syndrome, can have an impact on both reproductive outcomes and gynaecologic symptoms Understanding the cause of intrauterine adhesions and the common clinical presentation will increase awareness of the condition and guide the patien

A comprehensive review of Asherman's syndrome: causes, symptoms and treatment options.

What is new in this report? Substantial progress has been made since publishing previous practice guidelines on intrauterine adhesions (IUAs) [1]. Large-scale series, although retrospective, have reported clinical outcomes. Randomized controlled trials (RCTs) have investigated both primary and secondary adhesion prevention including solid and semi-solid barriers, although individual surgical techniques have not been rigorously studied. Recent human studies documenting successful pregnancy outcomes for bone marrow-derived stem cell (BMDSC) treatments following intermittent hysteroscopy are reported. This may provide a new avenue for research, although high quality data demonstrating efficacy are required before being introduced as a treatment option for women with symptomatic IUAs (Asherman syndrome). In order to encourage their wide dissemination, these guidelines are freely accessible on the GYNS and JMIG websites.

/pdf/aagl-practice-report-practice-guidelines-on-intrauterine-3nxufldwwg.pdf

AAGL practice report: practice guidelines on intrauterine adhesions developed in collaboration with the European Society of Gynaecological Endoscopy (ESGE).

Etiology, treatment, and reproductive prognosis of women with moderate-to-severe intrauterine adhesions.

Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to different concentrations of cisplatin was then assessed by measuring the cell viability using MTT assays. Next, miR-139 binding to the 3′UTR of ATP7A/B was confirmed using luciferase reporter gene assays. Finally, the combined effect of miR-139 and ATP7A/B on the chemoresistance of ovarian cancer cell was assessed. miR-139 expression was down-regulated in cisplatin-resistant ovarian cancer tissues (**P < 0.01) and reduced by cisplatin treatment in ovarian cell lines (*P < 0.05, **P < 0.01); miR-139 could enhance cisplatin-induced suppression on ovarian cancer cell viability, shown as reduced lC50 values; ATP7A and ATP7B protein levesincreased approximately 2 ~ fold-changein cisplatin-resistant cell lines. MiR-139 directly bound to the 3′UTR of ATP7A/B, respectively; miR-139 inhibition increased lC50 values whereas ATP7A/B knockdown reduced lC50 values of CAOV-3 and SNU119 cell lines under cisplatin treatment; the effect of miR-139 inhibition could be partially attenuated by ATP7A/B knockdown. MiR-139/ATP7A/B axis can be a reliable biomarker for ovarian cancer diagnosis, and may affect the chemoresistance of ovarian cancer to cisplatin-based chemotherapy; rescuing miR-139 expression thus to inhibit ATP7A/B might contribute to dealing with the chemoresistance of ovarian cancer.

MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy through regulation of ATP7A/B

Purpose: The aim of this study was to retrospectively analyse the clinical data of 122 patients with caesarean scar pregnancy (CSP) treated in our hospital, to compare the outcomes between high-intensity focused ultrasound (HIFU) and uterine artery embolisation (UAE). Materials and methods: Among the 122 patients, 76 patients were treated with HIFU followed by suction curettage under hysteroscopic guidance, 46 patients were treated with UAE followed by suction curettage under hysteroscopic guidance. Pain score, intraoperative blood loss in suction curettage under hysteroscopy guidance, time for vaginal bleeding, β-human chorionic gonadotropin (β-hCG) to return to normal level, normal menstruation recovery, hospital stay, and the adverse effects were all compared. Results: No statistically significant differences between the two groups in the intraoperative blood loss, hospital stay, time for β-human chorionic gonadotropin (β-hCG) to return to normal level, or time for normal menstruation recovery ...

A comparison of high-intensity focused ultrasound and uterine artery embolisation for the management of caesarean scar pregnancy.

Hysteroscopy for the diagnosis and treatment of pathologic changes in the uterine cavity in women with an intact hymen.

Aim

To assess three different methods in treating patients with cesarean scar pregnancy (CSP).



Methods

We evaluated pre-, intra- and postoperative conditions of 124 CSP patients in one of the three treatment groups, of which 37 patients underwent uterine curettage by hysteroscopy under ultrasound monitoring (group 1), 28 patients were treated with methotrexate followed by hysteroscopy (group 2) and 59 cases underwent uterine arterial embolization followed by hysteroscopy (group 3). The treatment options were determined based on the patients' conditions.



Results

Among all three groups, group 3 (uterine arterial embolization followed by hysteroscopy) had the least intraoperative blood loss and the highest success rate with curettage, but the highest hospitalization cost. Group 1 (only hysteroscopy) had the shortest length of hospitalization and the lowest cost, but the highest intraoperative blood loss and slowest recovery. Group 2 (methotrexate followed by hysteroscopy) had the longest period of hospitalization, and other indexes had fallen in between the other two groups.



Conclusion

Among the three methods, uterine arterial embolization followed by hysteroscopy is the safest and most efficient method without considering the cost of hospitalization. Patients with a low level of β-hCG may consider choosing hysteroscopy under ultrasound monitoring or methotrexate followed by hysteroscopy. The advantage is low cost of hospitalization; however, patients may be under relatively higher surgical risks and lower first time surgical success rate, especially for patients treated by hysteroscopy under ultrasound monitoring.

Yajun Wan

Papers

Etiology, treatment, and reproductive prognosis of women with moderate-to-severe intrauterine adhesions.

MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy through regulation of ATP7A/B

A comparison of high-intensity focused ultrasound and uterine artery embolisation for the management of caesarean scar pregnancy.

Hysteroscopy for the diagnosis and treatment of pathologic changes in the uterine cavity in women with an intact hymen.

Analysis of the efficacy of three treatment options for cesarean scar pregnancy management.