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The current paradigm of cancer medicine focuses on patient‐ and/or cancer‐specific treatments, which has led to continuous progress in the development of patient representatives (e.g., organoids) and cancer‐targeting carriers for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient‐specific microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell‐cell interactions can be harnessed to develop self‐homing nano‐targeting by using cancer cell‐derived nanovesicles (CaNVs). Hence, a tissueoid model of ovarian cancer (OC) is developed by culturing OC patient tissues in a 3D gel chip, whose microchannel networks enable perfusion to maintain tissue viability. A novel model of systemic cancer responses is approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs are produced to carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy metabolism, thereby increasing the test scope. This pioneer study cross‐validates drug responses from the OC clinic, tissueoid, and animal model by demonstrating the alignment of results in drug type‐specific efficiency, BRCA mutation‐dependent drug efficiency, and metabolism inhibition‐based anti‐cancer effects. Hence, this study provides a directional foundation to accelerate the discovery of patient‐specific drugs with CaNV application towards future precision medicine., A microchannel chip enables direct perfusion culture of ovarian cancer tissues from patients. Consequently, drug efficacies are cross‐validated with animal and clinical outcomes towards patient‐specific medicine. Considering spontaneous cancer cell aggregation upon propagation, cancer cell‐derived nanoparticles are produced to program self‐homing to target cancer sites. Loading of metabolic inhibitors to the particles represents a “trojan horse”‐like strategy.

Engineered ovary mimetics enable hormone autocrination and restore ovarian functions with reduction of menopause risks., The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.

Cancer stem cells (CSCs) constitute a subpopulation of transformed cells that possess intrinsic ability to undergo selfrenewal and differentiation, which drive tumour resistance and cancer recurrence. It has been reported that CSCs possess enhanced protection against oxidative stress induced by reactive oxygen species compared with nonstem-like cancer cells. In the present work, we investigated the role of heme oxygenase-1 (HO-1), a representative antioxidant enzyme, on the stemness and selfrenewal of human breast CSCs. We found that pharmacologic or genetic inhibition of HO-1 attenuated the sphere formation, whereas HO-1 inducers enhanced the number and the size of tumourspheres in breast CSCs. Carbon monoxide (CO) is endogenously generated as a consequence of degradation of heme by HO-1. The proportion of populations of CD44+/CD24- cells retaining CSC properties was increased in MDA-MB-231 cells treated with a CO-releasing molecule (CORM-2). Following CORM-2 treatment, the expression of Notch-1 and related genes Jagged-1 and Hes1 was increased, which was accompanied by the mammosphere formation. Taken together, these findings suggest that HO-1-derived CO production stimulates the formation of mammospheres in breast cancer cells through activation of Notch-1 signalling.

Overproduction of prostaglandin E2 (PGE2) has been linked to enhanced tumor cell proliferation, invasiveness and metastasis as well as resistance to apoptosis. 15-Keto prostaglandin E2 (15-keto PGE2), a product formed from 15-hydroxyprostaglandin dehydrogenase-catalyzed oxidation of PGE2, has recently been shown to have anti-inflammatory and anticarcinogenic activities. In this study, we observed that 15-keto PGE2 suppressed the phosphorylation, dimerization and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in human mammary epithelial cells transfected with H-ras (MCF10A-ras). 15-Keto PGE2 inhibited the migration and clonogenicity of MCF10A-ras cells. In addition, subcutaneous injection of 15-keto PGE2 attenuated xenograft tumor growth and phosphorylation of STAT3 induced by breast cancer MDA-MB-231 cells. However, a non-electrophilic analogue, 13,14-dihydro-15-keto PGE2 failed to inhibit STAT3 signaling and was unable to suppress the growth and transformation of MCF10A-ras cells. These findings suggest that the α,β-unsaturated carbonyl moiety of 15-keto PGE2 is essential for its suppression of STAT3 signaling. We observed that the thiol reducing agent, dithiothreitol abrogated 15-keto PGE2-induced STAT3 inactivation and disrupted the direct interaction between 15-keto PGE2 and STAT3. Furthermore, a molecular docking analysis suggested that Cys251 and Cys259 residues of STAT3 could be preferential binding sites for this lipid mediator. Mass spectral analysis revealed the covalent modification of recombinant STAT3 by 15-keto PGE2 at Cys259. Taken together, thiol modification of STAT3 by 15-keto PGE2 inactivates STAT3 which may account for its suppression of breast cancer cell proliferation and progression., Highlights • 15-Keto-prostaglandin E2 inhibits activation of STAT3 in MCF10A-ras cells. • 15-Keto-prostaglandin E2 suppresses the growth and transformation of MCF10A-ras cells. . • 15-Keto-prostaglandin E2 attenuated xenograft tumor growth and STAT3 phosphorylation. . • 15-Keto PGE2 modulates STAT3 by directly binding to its Cys259 residue.

Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and recurrence. Caveolin-1 (Cav-1) is a major protein of caveolae, which participates in various cellular functions, such as vesicle trafficking, cholesterol homeostasis, tumor progression, etc. In the present study, we investigated a role for Cav-1 in regulating the stemness of human breast cancer (MDA-MB-231) cells. Cav-1 expression was significantly lower in tumorspheres than in adherent cells. The silencing of Cav-1 enhanced stemness of MDA-MB-231 cells. Mechanistically, Cav-1 silencing was accompanied by enhanced expression of Bmi-1, which is a representative self-renewal regulator, and promoted epithelial-mesenchymal transition. In a CSC-like state, reduced Cav-1 depends on its destabilization through ubiquitin-proteasome degradation. We further found that Src-mediated phosphorylation of Cav-1 at the Tyr 14 residue is essential for its degradation. Taken together, these findings suggest that Cav-1 destabilization by Src may play a pivotal role in manifestation and maintenance of stemness in breast cancer cells.

To mitigate TOT complications we designed a modified TOT technique called canal TOT. We describe this new technique and evaluate its feasibility.Between October 2006 and June 2007, 105 consecutive women with stress urinary incontinence underwent a canal TOT procedure. Two oblique lateral incisions were made in the anterior vaginal wall and a suburethral canal was created between the incisions. Mesh was transferred beneath the canal. The subsequent canal TOT surgical steps were identical to those of the original TOT procedure. All patients were evaluated by urological examination and self-assessment questionnaires (Incontinence Impact Questionnaire-Short Form and Urogenital Distress Inventory-Short Form) preoperatively and 12 months postoperatively. Reportedly dyspareunia developed after the operation.A minimum 1-year followup was available in 99 patients. Median operative time was 25 minutes (range 15 to 50). No mesh erosion, retropubic hematoma or complete bladder retention developed. Transient postoperative voiding dysfunction and transient de novo urgency were observed in 2 (2.0%) and 8 patients (8.1%), respectively. Dyspareunia developed after surgery in 4 patients (4.0%). Postoperatively Incontinence Impact Questionnaire-Short Form and Urogenital Distress Inventory-Short Form scores decreased significantly (p0.05). Objective and subjective cure rates were 98.0% and 89.9%, respectively.The canal TOT procedure is feasible and effective for mitigating the complications of the original TOT procedure. This technique might be especially useful in patients with cystocele because of the paravaginal defect as well as in patients with obesity or prior vaginal surgery. However, a large-scale and long-term followup study is required to verify the effectiveness of this technique.

Parity is associated with weight retention and has long-lasting and detrimental effects on the health of women. Previous studies have shown that increasing parity was independently associated with an increased prevalence of metabolic syndrome. Postpartum weight is made up of several components including uterine and mammary tissues, body water (intracellular (ICW) and extracellular water (ECW)), and fat. These components change in variable amounts postpartum, thereby distinctly affecting the interpretation of individual weight retention; however, it is unclear which components contribute to weight retention. The aims of this longitudinal study were to evaluate changes in body composition during the postpartum period and to investigate their effects on weight retention. This prospective study examined 41 healthy, pregnant women who gave birth at Korea University Guro Hospital. We measured body composition at 2 days, 2 weeks, and 6 weeks postpartum using bioelectrical impedance analysis. Weight decreased during this postpartum period (P < 0.001); the postpartum weight retention from prepregnancy to 6 weeks postpartum was 4.43 ± 4.0 kg. Among various body composition components, ECW, ICW, total body water, and fat-free mass (FFM) decreased postpartum. However, fat mass (FM) and visceral fat area, the components that experienced the greatest changes, increased postpartum. Our results demonstrate that the postpartum period is associated with a preferential accumulation of adipose tissue in the visceral compartment, even though overall body weight is decreased. Further studies are needed to evaluate the changes in body composition over longer time periods and their long-term effects on health.

The aim of this study was to assess the feasibility and efficacy of laparoscopic myomectomy (LM) for large myomas. A subpopulation of 51 patients with myomas 8 cm or larger in diameter was selected from 155 patients who underwent LM at Kangbuk Samsung Hospital from July 2003 to November 2006. The mean age of the patients was 34.9 +/- 5.6 yr, mean parity was 0.6 +/- 0.9, and 8 patients had a previous operative history. The most common operative indication was a palpable abdominal mass (24 patients, 47%). The mean operating time was 85.6 +/- 38.9 min, and the mean diameter of the largest myoma was 9.3 +/- 1.8 cm. The mean change in hemoglobin concentration was 2.1 +/- 1.2 g/dL. Histopathological diagnosis included 49 patients of leiomyoma (96.1%) and 2 patients of leiomyoma with adenomyosis (3.9%). Postoperatively, a transfusion was done in 7 patients, and a case of subcutaneous emphysema was noted. None of the operations was switched to laparotomy. With the newly-developed screw and the port placement system that was modified from the Choi's 4-trocar method to obtain better surgical vision, LM of large myomas proved to be one of the efficient and feasible methods.