Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Hypersensitivity Reaction to Carboplatin in Gynecologic Cancer: A Case Report and a Review of the Literature.

A combination chemotherapy of paclitaxel plus carboplatin (TC) is the most frequently used regimen for gynecological malignancies. As long as it is effective, a carboplatin-containing combination chemotherapy is used for every relapse. This implies that the number of platinum administrations and the frequency of hypersensitivity reaction (HSR) increase as the prognosis improves. When a patient develops HSR to carboplatin, we have three options: 1) desensitizing and continuing to use carboplatin, 2) switching to other platinum drugs, or 3) changing to a non-platinum drug. Here we report an experience of an HSR to carboplatin in a patient with recurrent uterine carcinosarcoma. The patient was treated by surgery and TC therapy initially, resulting in no residual disease. The patient relapsed 18 months after the completion of the first-line chemotherapy and was treated with TC therapy again as second-line. An HSR to carboplatin occurred at the 10th cycle of TC in total. We replaced the carboplatin with cisplatin. A chemotherapy including cisplatin and adriamycin was repeated without further HSR. We reviewed the literature regarding HSR to carboplatin and in this paper we summarize the management for dealing with it.

Strategies for the Treatment of Cervical Cancer with Bulky Pelvic Lymph Nodes: An Overview of the Current Evidence.

Cervical cancer commonly metastasizes first to the pelvic lymph nodes and then subsequently spreads to distant organs, making lymph node metastases the most significant prognostic factor in cervical cancer, and the strategy for its treatment directly influences prognosis. This review focuses on the treatment strategies for cases of cervical cancer with bulky pelvic lymph nodes. Concurrent chemoradiotherapy is the standard treatment modality for patients with pelvic lymph node metastases, but it is inadequate for bulky pelvic lymph nodes. Accordingly, surgical resection of the bulky lymph nodes has been attempted, and its therapeutic significance has been reported. If the bulky lymph nodes are unresectable, definitive concurrent chemoradiotherapy is performed. If it yields an inadequate degree of lymph node shrinkage, boosted radiation should be considered. The addition of chemotherapy after concurrent chemoradiotherapy has also been reported to be effective in patients with lymph node metastases and is currently being evaluated in clinical trials.

Crystal Structures of the Putative Isocitrate Dehydrogenase from Sulfolobus tokodaii Strain 7 in the Apo and NADP+-Bound Forms.

Isocitrate dehydrogenase is a catabolic enzyme that acts during the third step of the tricarboxylic acid cycle. The hypothetical protein ST2166 from the archaeon Sulfolobus tokodaii was isolated and crystallized. It shares high primary structure homology with prokaryotic NADP+-dependent IDHs, suggesting that these enzymes share a common enzymatic mechanism. The crystal structure of ST2166 was determined at 2.0 Å resolution in the apo form, and then the structure of the crystal soaked with NADP+ was also determined at 2.4 Å resolution, which contained NADP+ bound at the putative active site. Comparisons between the structures of apo and NADP+-bound forms and NADP-IDHs from other prokaryotes suggest that prokaryotic NADP-IDHs recognize their cofactors using conserved Lys335, Tyr336, and Arg386 in ST2166 at the opening cleft before the domain closure.

Crystal Structure of the 11-cis Isomer of Pharaonis Halorhodopsin: Structural Constraints on Interconversions among Different Isomeric States.

Like other microbial rhodopsins, the light driven chloride pump halorhodopsin from Natronomonas pharaonis (pHR) contains a mixture of all-trans/15-anti and 13-cis/15-syn isomers in the dark adapted state. A recent crystallographic study of the reaction states of pHR has shown that reaction states with 13-cis/15-syn retinal occur in the anion pumping cycle that is initiated by excitation of the all-trans isomer. In this study, we investigated interconversions among different isomeric states of pHR in the absence of chloride ions. The illumination of chloride free pHR with red light caused a large blue shift in the absorption maximum of the retinal visible band. During this "red adaptation", the content of the 11-cis isomer increased significantly, while the molar ratio of the 13-cis isomer to the all-trans isomer remained unchanged. The results suggest that the thermally activated interconversion between the 13-cis and the all-trans isomers is very rapid. Diffraction data from red adapted crystals showed that accommodation of the retinal chromophore with the 11-cis/15-syn configuration was achieved without a large change in the retinal binding pocket. The measurement of absorption kinetics under illumination showed that the 11-cis isomer, with a λmax at 565 nm, was generated upon excitation of a red-shifted species (λmax = 625 nm) that was present as a minor component in the dark adapted state. It is possible that this red-shifted species mimics an O-like reaction state with 13-cis/15-syn retinal, which was hypothesized to occur at a late stage of the anion pumping cycle.

Crystal structures of the L1, L2, N, and O states of pharaonis halorhodopsin.

Halorhodopsin from Natronomonas pharaonis (pHR) functions as a light-driven halide ion pump. In the presence of halide ions, the photochemical reaction of pHR is described by the scheme: K→ L1 → L2 → N → O → pHR' → pHR. Here, we report light-induced structural changes of the pHR-bromide complex observed in the C2 crystal. In the L1-to-L2 transition, the bromide ion that initially exists in the extracellular vicinity of retinal moves across the retinal Schiff base. Upon the formation of the N state with a bromide ion bound to the cytoplasmic vicinity of the retinal Schiff base, the cytoplasmic half of helix F moves outward to create a water channel in the cytoplasmic interhelical space, whereas the extracellular half of helix C moves inward. During the transition from N to an N-like reaction state with retinal assuming the 13-cis/15-syn configuration, the translocated bromide ion is released into the cytoplasmic medium. Subsequently, helix F relaxes into its original conformation, generating the O state. Anion uptake from the extracellular side occurs when helix C relaxes into its original conformation. These structural data provide insight into the structural basis of unidirectional anion transport.

Structure of archaerhodopsin-2 at 1.8†Šresolution.

Archaerhodopsin-2 (aR2), the sole protein found in the claret membrane of Halorubrum sp. Aus-2, functions as a light-driven proton pump. In this study, structural analysis of aR2 was performed using a novel three-dimensional crystal prepared by the successive fusion of claret membranes. The crystal is made up of stacked membranes, in each of which aR2 trimers are arranged on a hexagonal lattice. This lattice structure resembles that found in the purple membrane of H. salinarum, except that lipid molecules trapped within the trimeric structure are not distributed with perfect threefold symmetry. Nonetheless, diffraction data at 1.8 Šresolution provide accurate structural information about functionally important residues. It is shown that two glutamates in the proton-release channel form a paired structure that is maintained by a low-barrier hydrogen bond. Although the structure of the proton-release pathway is highly conserved among proton-pumping archaeal rhodopsins, aR2 possesses the following peculiar structural features: (i) the motional freedom of the tryptophan residue that makes contact with the C13 methyl group of retinal is restricted, affecting the formation/decay kinetics of the L state, and (ii) the N-terminal polypeptide folds into an Ω-loop, which may play a role in organizing the higher-order structure.

Crystal structure of squid rhodopsin.

Invertebrate phototransduction uses an inositol-1,4,5-trisphosphate signalling cascade in which photoactivated rhodopsin stimulates a G(q)-type G protein, that is, a class of G protein that stimulates membrane-bound phospholipase Cbeta. The same cascade is used by many G-protein-coupled receptors, indicating that invertebrate rhodopsin is a prototypical member. Here we report the crystal structure of squid (Todarodes pacificus) rhodopsin at 2.5 A resolution. Among seven transmembrane alpha-helices, helices V and VI extend into the cytoplasmic medium and, together with two cytoplasmic helices, they form a rigid protrusion from the membrane surface. This peculiar structure, which is not seen in bovine rhodopsin, seems to be crucial for the recognition of G(q)-type G proteins. The retinal Schiff base forms a hydrogen bond to Asn 87 or Tyr 111; it is far from the putative counterion Glu 180. In the crystal, a tight association is formed between the amino-terminal polypeptides of neighbouring monomers; this intermembrane dimerization may be responsible for the organization of hexagonally packed microvillar membranes in the photoreceptor rhabdom.

Cytokine release syndrome induced by immune checkpoint inhibitor treatment for uterine cervical cancer recurrence: A case report.

Cytokine release syndrome (CRS) is a systemic inflammatory condition caused by an excessive immune response and cytokine overproduction. CRS is a life-threatening condition that is often associated with chimeric antigen receptor T-cell therapy. Despite the increased use of immune checkpoint inhibitors (ICIs), ICI-induced CRS remains rare. The present study describes a case of CRS that occurred after the administration of ICIs for recurrent adenocarcinoma of the uterine cervix. A 49-year-old woman received paclitaxel, carboplatin and pembrolizumab for recurrent cervical adenocarcinoma. On day 27 of the third cycle, the patient was admitted with a fever and suspected pyelonephritis. The following day, hypotension, upper respiratory symptoms and myalgia of the extremities were noted, and the left ventricular ejection fraction (LVEF) was decreased to 20%. Multiorgan failure (MOF) occurred, and the patient received ventilator support and continuous hemodiafiltration. Rhabdomyolysis, pancreatitis, erythema multiforme and enteritis were observed. CRS was diagnosed based on elevated ferritin and IL-6 levels. Steroid pulse therapy was administered; however, the MOF did not improve and the anti-IL-6-receptor monoclonal antibody tocilizumab (TOC) was administered. Subsequently, the LVEF improved to 50%, and the patient was removed from the ventilator on day 4 and from the continuous hemodiafiltration unit on day 6 after TOC administration. The patient was discharged on day 21. In conclusion, considering that ICI-induced CRS is a rare but severe complication, fever and other systemic conditions following ICI administration should be monitored.

Large deformation of helix F during the photoreaction cycle of Pharaonis halorhodopsin in complex with azide.

Halorhodopsin from Natronomonas pharaonis (pHR), a retinylidene protein that functions as a light-driven chloride ion pump, is converted into a proton pump in the presence of azide ion. To clarify this conversion, we investigated light-induced structural changes in pHR using a C2 crystal that was prepared in the presence of Cl(-) and subsequently soaked in a solution containing azide ion. When the pHR-azide complex was illuminated at pH 9, a profound outward movement (∼4 Å) of the cytoplasmic half of helix F was observed in a subunit with the EF loop facing an open space. This movement created a long water channel between the retinal Schiff base and the cytoplasmic surface, along which a proton could be transported. Meanwhile, the middle moiety of helix C moved inward, leading to shrinkage of the primary anion-binding site (site I), and the azide molecule in site I was expelled out to the extracellular medium. The results suggest that the cytoplasmic half of helix F and the middle moiety of helix C act as different types of valves for active proton transport.

Crystal structure of deltarhodopsin-3 from Haloterrigena thermotolerans.

Deltarhodopsin, a new member of the microbial rhodopsin family, functions as a light-driven proton pump. Here, we report the three-dimensional structure of deltarhodopsin (dR3) from Haloterrigena thermotolerans at 2.7 Å resolution. A crystal belonging to space group R32 (a, b = 111.71 Å, c = 198.25 Å) was obtained by the membrane fusion method. In this crystal, dR3 forms a trimeric structure as observed for bacteriorhodopsin (bR). Structural comparison of dR with bR showed that the inner part (the proton release and uptake pathways) is highly conserved. Meanwhile, residues in the protein-protein contact region are largely altered so that the diameter of the trimeric structure at the cytoplasmic side is noticeably larger in dR3. Unlike bR, dR3 possesses a helical segment at the C-terminal region that fills the space between the AB and EF loops. A significant difference is also seen in the FG loop, which is one residue longer in dR3. Another peculiar property of dR3 is a highly crowded distribution of positively charged residues on the cytoplasmic surface, which may be relevant to a specific interaction with some cytoplasmic component.

Association of UBE2L6 and ABCB6 Expression With Platinum Resistance in Serous Ovarian Carcinoma.

BACKGROUND/AIM: Platinum-based drugs are the standard treatment for ovarian cancer, and platinum resistance is a major problem. A previous study has reported that the UBE2L6 expression is elevated in cisplatin-resistant cells, which in turn leads to cisplatin resistance by modulating the transcriptional expression of ABCB6. The present study aimed to investigate the expression of UBE2L6 and ABCB6 in ovarian carcinoma and to evaluate the association between these markers and platinum resistance. PATIENTS AND METHODS: Ninety-two patients diagnosed with serous ovarian carcinoma (SOC) were enrolled in this study. Tissue samples were collected from these patients and analysed using immunohistochemistry to assess the expression of UBE2L6 and ABCB6. RESULTS: UBE2L6 and ABCB6 staining was positive in 41 (44.6%) and 46 (50.0%) cases, respectively. UBE2L6 expression was statistically significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.008). Both UBE2L6 and ABCB6 were significantly associated with platinum sensitivity (p<0.001 and p<0.001). A positive correlation was observed between the expression levels of UBE2L6 and ABCB6 (r=0.673, p<0.001). Progression-free survival (PFS) was significantly longer in the UBE2L6 negative group than that in the positive group (median PFS, 31.4 vs. 11.1 months, p<0.01) and in the ABCB6 negative group than that in the positive group (median PFS, 29.6 vs. 12.2 months, p<0.01). CONCLUSION: UBE2L6 and ABCB6 expression is associated with the prognosis of SOC. UBE2L6 and ABCB6 may be potential biomarkers of platinum-resistant ovarian cancer.

Crystal structure of the O intermediate of the Leu93→Ala mutant of bacteriorhodopsin.

The lifetime of the O intermediate of bacteriorhodopsin (BR) is extended by a factor of ∼250 in the Leu93-to-Ala mutant (BR_L93A). To clarify the structural changes occurring in the last stage of the proton pumping cycle of BR, we crystallized BR_L93A into a hexagonal P622 crystal. Diffraction data from the unphotolyzed state showed that the deletion of three carbon atoms from Leu93 is compensated by the insertion of four water molecules in the cytoplasmic vicinity of retinal. This insertion of water is suggested to be responsible for the blue-shifted λ(max) (540 nm) of the mutant. A long-lived substate of O with a red-shifted λ(max) (~565 nm) was trapped when the crystal of BR_L93A was flash-cooled after illumination with green light. This substate (O(slow)) bears considerable similarity to the M intermediate of native BR; that is, it commonly shows deformation of helix C and the FG loop, downward orientation of the side chain of Arg82, and disruption of the Glu194/Glu204 pair. In O(slow), however, the main chain of Lys216 is less distorted and retinal takes on the 13-cis/15-syn configuration. Another significant difference is seen in the pH dependence of the structure of the proton release group, the pK(a) value of which is suggested to be much lower in O(slow) than in M.

Long-Term Tocolysis With Magnesium Sulfate as a Risk Factor for Low Bone Mass: A Case Series.

Pregnancy and lactation-associated osteoporosis (PLO) is a disease caused by vertebral compression fracture, and it is characterized by low back pain during pregnancy or the postpartum period. However, it is difficult to predict and prevent PLO prepartum in high-risk groups. Recently, long-term tocolysis with magnesium sulfate (MgSO4) has been reported to be associated with PLO. The purpose of this case series was to assess postpartum bone mass after long-term tocolysis with MgSO4 and accumulated doses of MgSO4. We report the case of a pregnant woman with vertebral compression fractures during pregnancy following long-term tocolysis with MgSO4. We investigated whether long-term tocolysis with MgSO4 was a high risk factor for PLO. Therefore, we retrospectively evaluated bone mineral density after delivery in nine women who had long-term tocolysis with MgSO4 (more than 8 days) for treatment of threatened preterm birth at our hospital from January 2020 to December 2020. The age of the women was between 20 and 41 years (mean age, 30 years). The body mass index of the women was between 18.1 and 25.4 kg/m2 (mean 20.0 kg/m2). Three women had a positive smoking history, and none had a family history of osteoporosis. The average duration of tocolysis with MgSO4 was 11 - 97 days. The accumulated doses of MgSO4 were between 168 and 3,756 g. Four of nine cases were diagnosed with low bone mass of young adult mean (YAM) value ≤ 80%. Of them, one case (accumulated doses of MgSO4: 1,260 g) was diagnosed with PLO of YAM value ≤ 70%, and one case (accumulated doses of MgSO4: 3,756 g) was diagnosed with bone fracture with a YAM value of ≤ 70%. Long-term tocolysis with MgSO4 may be suggested as one of the risk factors of PLO. Nutritional guidance and rehabilitation are important interventions for target patients.

Prognostic significance of intra-tumoral budding in high-grade serous ovarian carcinomas.

Intra-tumoral budding (ITB) has been well demonstrated to be an independent risk factor for adverse outcomes in colorectal carcinoma. This study investigated the prognostic significance of ITB in high-grade serous ovarian carcinomas (HGSOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The histopathologic examination with scoring of p53 expression showed them to be 80 HGSOCs and 4 low-grade serous ovarian carcinomas (LGSOCs). ITB was found in 64 (80.0%) of the 80 HGSOCs and 1 (25.0%) of 4 LGSOCs. The presence of ITB in HGSOC was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, the presence of Lymph node metastasis, and the presence of lymphovascular space invasion (LVSI). The median progression-free survival (PFS) was 18 months in patients with HGSOC with ITB and 36 months in patients with HGSOC without ITB (P = 0.006), and their median overall survival (OS) was 50 months and 60 months (P = 0.060). The multivariate analysis revealed that ITB was not an independent prognostic factor. ITB is a cost-effective prognostic indicator for patients with HGSOC and ITB in ovarian tumor tissue is considered a useful histological biomarker of the progression of HGSOCs.

Difficulties in Differentiating Hypertensive Disorders of Pregnancy With Polyarteritis Nodosa.

Polyarteritis nodosa (PAN) is characterized by medium- or small-sized artery vasculitis with vessel wall inflammation and necrosis of muscular arteries, commonly presenting with fatigue, fever, weight loss, and joint pain. PAN in pregnancy is rare and is associated with worsening of vasculitis after delivery, resulting in myocardial infarction and heart failure which frequently lead to maternal death. We report a case of hypertensive disorders of pregnancy (HDP), which is difficult to differentiate from PAN. A 27-year-old multigravida was diagnosed with PAN 4 years prior after experiencing fever and lower extremity skin rash. During her PAN remission, she conceived her second pregnancy and opted to discontinue PAN medication and declined antihypertensive medications. At 22 weeks of gestation, her blood pressure was elevated to 200/100 mm Hg without proteinuria, for which she was admitted to our hospital. She was diagnosed with HDP-chronic hypertension without PAN recurrence due to the absence of PAN-specific skin or joint symptoms according to the PAN diagnostic criteria. Antihypertensive medication was administered. At 30 weeks of gestation, her blood pressure was poorly controlled and she developed proteinuria, which led to a diagnosis of superimposed preeclampsia that necessitated emergency cesarean section delivery. After delivery, her blood pressure was immediately controlled using antihypertensive medication. Our case report highlights the importance of carefully managing HPD as a serious complication of PAN.

Retrospective analysis of prognosis using the Gynecology Oncology Group score of stage IB-IIA node negative uterine cervical cancer after radical hysterectomy and trachelectomy.

There is currently controversy regarding the criteria for low and intermediate risk of cervical cancer (CC) after surgery. In the present study, the Gynecology Oncology Group (GOG) score was used to detect intermediate risk. Adjuvant radiotherapy was applied in the case of a GOG score >120. The present study aimed to evaluate the validity of the recurrence risk classification using the GOG score for stage IB-IIA node-negative CC. All cases of stage IB-IIA node-negative CC who underwent radical surgery between February 2007 and December 2015 were retrospectively reviewed. The GOG scores were determined from clinical and pathological findings and accordingly, subjects were divided into 4 groups: A, ≤40; B, >40 and ≤70; C, >70 and ≤120; and D, >120. Overall survival (OS) and recurrence-free survival (RFS) curves were generated using the Kaplan-Meier method. The log-rank test produced an estimated P-value by comparing the OS and RFS of group A (low-score group) with those of others. The present study included 61 patients (mean age, 47.82 years; age range, 22-76 years) and the median follow-up was 79 (39-149) months. Of these, 60 patients were observed for at least 60 months. During the follow-up period, the OS and RFS rates of group C were 94.7 and 84.2%, respectively, while those of group D were 100 and 91.7%, respectively; the OS and RFS of groups A and B were 100%. Log-rank tests for all OS and RFS indicated no significant differences compared to group A. It was indicated that a GOG score ≤70 does not require adjuvant therapy; however, a GOG score >70 requires consideration of adjuvant therapy based on the risk factors which constitute the score.

Functionally important structural elements of the cyanobacterial clock-related protein Pex.

Pex, a clock-related protein involved in the input pathway of the cyanobacterial circadian clock system, suppresses the expression of clock gene kaiA and lengthens the circadian period. Here, we determined the crystal structure of Anabaena Pex (AnaPex; Anabaena sp. strain PCC 7120) and Synechococcus Pex (SynPex; Synechococcus sp. strain PCC 7942). Pex is a homodimer that forms a winged-helix structure. Using the DNase I protection and electrophoresis mobility shift assays on a Synechococcus kaiA upstream region, we identified a minimal 25-bp sequence that contained an imperfectly inverted repeat sequence as the Pex-binding sequence. Based on crystal structure, we predicted the amino acid residues essential for Pex's DNA-binding activity and examined the effects of various Ala-substitutions in the alpha3 helix and wing region of Pex on in vitro DNA-binding activity and in vivo rhythm functions. Mutant AnaPex proteins carrying a substitution in the wing region displayed no specific DNA-binding activity, whereas those carrying a substitution in the alpha3 helix did display specific binding activity. But the latter were less thermostable than wild-type AnaPex and their in vitro functions were defective. We concluded that Pex binds a kaiA upstream DNA sequence via its wing region and that its alpha3 helix is probably important to its stability.

Structural divergence and functional versatility of the rhodopsin superfamily.

Seven-transmembrane-helix retinylidene proteins, which constitute the rhodopsin superfamily, have been discovered in diverse species, including Archaea, Eubacteria, fungi, algae and animals. Some members of this super-family were specialized to function as light-driven proton pumps, light-driven chloride pumps, photoisomerases, or light-gated ion channels, where the photochemical reactions are self-completed without interactions with other proteins. Other members evolved to acquire the ability to modulate soluble cytoplasmic or membrane-embedded signal transducers. During the last decade, high-resolution crystal structures were reported for ten members of the rhodopsin superfamily; viz., four proton pumps, two chloride pumps, two microbial photosensors and two visual pigments. Comparison of these structures provides us with a hint to elucidate the common structural motif that is utilized to stabilize their tertiary structures as well as unique architectures that are relevant to specific functions.

UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6.

BACKGROUND: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. OBJECTIVE: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. METHODS: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. RESULTS: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. CONCLUSION: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.