Successful Treatment of Metastatic Gallbladder Carcinoma with a High Tumor Mutational Burden Using Pembrolizumab.

A woman in her 70s presented with gallbladder carcinoma with liver metastases and peritoneal dissemination. After standard chemotherapy failed, a liver biopsy was performed. A FoundationOne CDx analysis showed that the tumor mutational burden (TMB) was high (34 mutations/megabase). Treatment with pembrolizumab, which is an immune checkpoint inhibitor (ICI), resulted in a partial response, and there were no significant immune-related adverse events. According to recently published reports, the frequency of TMB-high biliary tract cancer (BTC) is 3.4-4%, which makes it extremely rare. In conclusion, ICIs may be effective in patients with TMB-high BTC.

Dosimetric Comparison of 3D Conformal Radiotherapy (3D-CRT), Intensity-Modulated Radiotherapy (IMRT), and Volumetric-Modulated Arc Therapy (VMAT) in Cardiac-Sparing Whole Lung Irradiation.

Introduction Whole lung irradiation (WLI) is used for the treatment of lung metastasis in Wilms tumor and Ewing sarcoma; however, cardiac complications are one of the concerns. We report the dosimetric advantages of WLI using volumetric-modulated arc therapy (VMAT) and present a dosimetric comparison of VMAT with anteroposterior-posteroanterior (AP-PA) and static-field intensity-modulated radiation therapy (IMRT). Additionally, we evaluated the dosimetric impact of respiratory motion and intra-fractional motion during VMAT treatment. Methods Seven patients were recruited in this study. AP-PA, IMRT, one-isocenter (1-IC) VMAT, and 2-IC VMAT were planned on the maximum inspiration and expiration CT, respectively. The prescribed dose was 15 Gy in 10 fractions. To determine the effects of respiratory motion, the CT series was replaced and the dose was evaluated while maintaining the beam information. To determine the effect of patient motion, perturbed dose calculations were performed using a two-IC VMAT. The perturbation doses were calculated by shifting only the IC of the one side beam by 3 mm or 5 mm in the right-to-left (RL) direction. Results The mean heart dose was 1467.0 cGy, 790.0 cGy, 764.2 cGy, and 738.4 cGy for AP-PA, IMRT, 1-IC VMAT, and 2-IC VMAT, respectively. When the expiration CT plan was recalculated with inspiration CT, Dmax increased approximately by 8%. In the 2-IC VMAT plan, the D50%, D98%, and D2% dose differences were within ±2%, even with a 5 mm IC shift. Conclusion We confirmed a significant dosimetric advantage of VMAT over other techniques. 2-IC VMAT should be considered an effective treatment option during irradiation for large target volumes.

Residual image registration error by fiducial markers in accelerated partial breast irradiation using C-arm linac: a phantom study.

External beam accelerated partial breast irradiation (APBI) is an alternative treatment for patients with early-stage breast cancer. The efficacy of image-guided radiotherapy (IGRT) using fiducial markers, such as gold markers or surgical clips, has been demonstrated. However, the effects of respiratory motion during a single fraction have not been reported. This study aimed to evaluate the residual image registration error of fiducial marker-based IGRT by respiratory motion and propose a suitable treatment strategy. We developed an acrylic phantom embedded with surgical clips to verify the registration error under moving conditions. The frequency of the phase difference in the respiratory cycle due to sequential acquisition was verified in a preliminary study. Fiducial marker-based IGRT was then performed in ten scenarios. The residual registration error (RRE) was calculated on the basis of the differences in the coordinates of clips between the true position if not moved and the last position. The frequencies of the phase differences in 0.0-0.99, 1.0-1.99, 2.0-2.99, 3.0-3.99, and 4.0-5.0 mm were 23%, 24%, 22%, 20%, and 11%, respectively. When assuming a clinical case, the mean RREs for all directions were within 1.0 mm, even if respiratory motion of 5 mm existed in two axes. For APBI with fiducial marker-based IGRT, the introduction of an image registration strategy that employs stepwise couch correction using at least three orthogonal images should be considered.

VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury.

BACKGROUND: Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury. METHODS: LPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells. RESULTS: The early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosis via upregulation of integrin αv in the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages. CONCLUSIONS: VEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.

TAFRO syndrome complicated by porto-sinusoidal vascular liver disease with portal hypertension: a case report.

Porto-sinusoidal vascular liver disease (PSVD) is a disorder that can cause portal hypertension without liver cirrhosis. TAFRO syndrome is a systemic inflammatory disorder with a background of immunological abnormalities. We report a case of TAFRO syndrome complicated by PSVD with portal hypertension. A 39-year-old man developed refractory ascites and esophageal varices. Lymph node histology revealed multicentric Castleman disease-like features. Intravenous methylprednisolone and tocilizumab therapy improved ascites and renal dysfunction, but the patient developed severe infections. The diagnosis of TAFRO syndrome in patients complicated by PSVD with portal hypertension encourages the consideration of appropriate treatment for these patients.

Assessment of visual feedback system for reproducibility of voluntary deep inspiration breath hold in left-sided breast radiotherapy.

INTRODUCTION: Deep inspiration breath-hold (DIBH) for left-sided breast cancer radiotherapy reduces the dose exposure of the heart and left anterior descending coronary artery. DIBH requires the patient to maintain an adequate breath-hold position during their daily radiotherapy fraction. This study aimed to assess the reproducibility of the breath-hold position by implementing DIBH with visual feedback (VF) system. METHODS: Forty-three patients who underwent left-sided radiotherapy with DIBH were reviewed. Data from 35 patients who underwent DIBH with VF (VF-DIBH) were compared with data from 8 patients who underwent DIBH with audio coaching (AC-DIBH). Reproducibility during radiotherapy was evaluated using the portal images obtained. Images were acquired daily during the tangential field treatment with DIBH. The distances between the field edge and chest wall at the central beam axis were manually measured on the portal image and digital reconstruction radiograph (DRR). The displacements of the chest wall during radiotherapy were assessed by subtracting the measurement made on the portal image from the DRR measurement. The overall average distances for the VF-DIBH and AC-DIBH cohorts were compared to assess reproducibility. The statistical analysis was performed using Mann-Whitney U tests (p < 0.05). RESULTS: The mean chest wall displacement (±2 SD) was 0.59 ± 3.64 mm for VF-DIBH and 2.09 ± 4.96 mm for AC-DIBH, respectively. This value differed significantly between the VF-DIBH and AC-DIBH cohorts (p < 0.001). CONCLUSION: In DIBH radiotherapy, the implementation of VF was confirmed to improve breath-hold position reproducibility, and the utility of VF for DIBH was demonstrated.

A 55-Year-Old Japanese Man with Multiple Sclerosis Diagnosed with Disseminated Tuberculosis Identified by Liver Function Abnormalities: A Case Report.

BACKGROUND Reactivation of latent tuberculosis infection (LTBI) is a recognized complication of immunosuppressive treatment. However, immunosuppressed patients are also at risk of hematogenous disseminated spread from a primary infection with Mycobacterium tuberculosis. This report presents the case of a 55-year-old Japanese man with a 12-year history of multiple sclerosis who was hospitalized with worsening neurological symptoms and was diagnosed with disseminated tuberculosis identified by abnormalities on liver function test results. CASE REPORT A 55-year-old Japanese man was admitted to our hospital for the treatment of multiple sclerosis with worsening symptoms. He showed mild liver dysfunction at the time of admission. A laparoscopy and biopsy were performed to identify the cause of the liver dysfunction, which was the only positive finding. The liver surface was studded with yellowish-white nodular lesions. Histological examination of a liver biopsy specimen revealed a granuloma without caseous necrosis. The patient was suspected of having tuberculosis. Although the results of an interferon-γ-releasing assay were indeterminate, asymptomatic disseminated tuberculosis was diagnosed from the serum adenosine deaminase levels, a caseating granuloma in the cervical lymph node, detection of acid-fast bacilli DNA in the cervical lymph nodes on polymerase chain reaction, and tuberculin skin test findings. Anti-tuberculosis treatment led to improvement in the liver function test findings. CONCLUSIONS This case has highlighted that tuberculosis may have an atypical presentation in the immunosuppressed patient. In addition to the reactivation of LTBI, hematogenous spread of primary tuberculosis may result in disseminated disease involving multiple organs and requiring emergency treatment.

[A Case of Hepatocellular Carcinoma Complicated by Liver Metastasis of Colon Cancer during the Course of Treatment].

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.

Imatinib and nutritional support can make successful treatment for a case of huge liver metastasis of duodenal gastrointestinal stromal tumor that initially showed jaundice and cachexia.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.

A 51-Year-Old Woman with Drug-Induced Hypersensitivity Syndrome Associated with Carbamazepine, Reactivation of Human Herpesvirus 6, and Acute Liver Failure: A Case Report.

BACKGROUND Infection with human herpesvirus 6 (HHV-6) is a recognized risk factor for the development of drug-induced hypersensitivity syndrome (DIHS). DIHS is a systemic autoimmune condition that presents with mucocutaneous lesions of varying severity and comprises 3 subtypes: toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Here, we describe the case of a 51-year-old woman with a diagnosis of DIHS associated with carbamazepine, reactivation of HHV-6, and acute liver failure, which was consistent with DRESS. CASE REPORT We present the case of a 51-year-old Japanese woman who had been taking carbamazepine for epilepsy for the past 3 weeks. She presented with a fever, liver dysfunction, eosinophilia, and the sudden appearance of a skin rash. Steroid therapy was started for suspected drug-induced liver injury. The skin eruption disappeared, and liver dysfunction showed an improving trend. However, after stopping steroid, the pyrexia and eosinophilia reappeared. Therefore, prednisolone was re-administrated. HHV-6 DNA was detected, so HHV-6 reactivation was confirmed. Carbamazepine was stopped, and the clinical manifestations improved. She was ultimately diagnosed with DIHS, consistent with DRESS, associated with carbamazepine and HHV-6 reactivation, and liver dysfunction was assessed histologically. Therefore, the drug-related hepatotoxicity of carbamazepine played a role in causing liver damage rather than HHV-6 infection at that time. CONCLUSIONS We describe a case of DIHS that was also associated with acute liver failure, consistent with DRESS. The case highlights the importance of making the correct diagnosis, as well as the management of mucocutaneous lesions and other systemic conditions (including acute liver failure).

Anomalous atrium associated with persistent left superior vena cava.

Persistent left superior vena cava (PLSVC) is the most common venous anomaly with an incidence of 0.3-0.5% in the general population. Here, we report a rare case of PLSVC with anomalous atrium in a cadaver during the student's dissection session at the University of Tsukuba. In this case, the coronary sinus had merged with the right atrium to form an enlarged sac-like structure and received systemic venous flow including inflow from the PLSVC. The roof of the coronary sinus with the right atrium was thicker than that of the control cases. We further found that the distance between the sinoatrial node and the opening of the coronary sinus was slightly more than half of that in control cases. This variant appears interesting and is worth reporting for developmental and clinical consideration.

Hepatitis B virus reactivation after successful treatment of hepatitis C virus with sofosbuvir and ribavirin: A case report and literature review.

RATIONALE: Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS: In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES: This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS: The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES: Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS: Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.

Use of the Illumina EPIC methylation array for epigenomic research in the crab-eating macaque (Macaca fascicularis).

BACKGROUND: Commercially available Illumina DNA methylation arrays (HumanMethylation 27K, HumanMethylation450, and MethylationEPIC BeadChip) can be used for comprehensive DNA methylation analyses of not only the human genome but also other mammalian genomes, ranging from those of nonhuman primates to those of rodents. However, practical application of the EPIC array to the crab-eating macaque has not been reported. METHODS: Through bioinformatic analyses involving cross-species comparison and consideration of probe performance, we selected array probes that can be reliably used for the crab-eating macaque genome. A DNA methylation assay using an EPIC array was performed on genomic DNA extracted from the brains of five crab-eating macaques. The obtained DNA methylation data were compared with a publicly available dataset. RESULTS: Among the 865 918 probes in the EPIC array, a total of 183 509 probes (21.2%) were selected as high-confidence array probes in the crab-eating macaque. Subsequent comparisons revealed that the data from these probes showed good concordance with other DNA methylation datasets of the crab-eating macaque. CONCLUSION: The selected high-confidence array probes would be useful for high-throughput DNA methylation assays of the crab-eating macaque.

Asymptomatic colonic intussusception in ulcerative colitis: a case report.

Intussusception in adults is, especially with ulcerative colitis (UC), rare and only described in a few cases. Most adult patients with intussusception develop abdominal pain or other symptoms of bowel obstruction. This case describes an 18-year-old male with UC who treated with 5-aminosalycilicacid and underwent annual screening colonoscopies. Two attempts revealed that it was impossible to achieve total surveillance through the colonoscopy because multiple polyps were preventing the colonoscope from traversing the entire colon. Therefore, CT scan was performed and colonic intussusception was discovered incidentally, and the patient underwent elective laparoscopic total colectomy. To the best of our knowledge, this is the first reported case of asymptomatic intussusception in the adult patient with UC. When total surveillance colonoscopy fails to yield results, a CT may be advisable to pick up such an asymptomatic intussusception.

Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab.

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

Feasibility of IVIM parameters from diffusion-weighted imaging at 11.7T MRI for detecting ischemic changes in common carotid artery occlusion rats.

This study aimed to investigate whether intravoxel incoherent motion (IVIM) parameters can identify ischemic changes in the rat cerebral cortex using a preclinical ultra-high-field 11.7 Tesla magnetic resonance imaging (11.7TMRI) scanner. In nine female Wistar rats (eight weeks old), diffusion-weighted imaging (DWI) for IVIM analysis was successfully performed before (Pre) and after unilateral (UCCAO) and bilateral (BCCAO) common carotid artery occlusion. From the acquired DWI signals averaged in six regions of interest (ROI) placed on the cortex, volume fraction of perfusion compartment (F), pseudo diffusion coefficient (D*), F × D* and apparent diffusion coefficient (ADC) were determined as IVIM parameters in the following three DWI signal models: the bi-exponential, kurtosis, and tri-exponential model. For a subgroup analysis, four rats that survived two weeks after BCCAO were assigned to the long survival (LS) group, whereas the non-LS group consisted of the remaining five animals. Each IVIM parameter change among three phases (Pre, UCCAO and BCCAO) was statistically examined in each ROI. Then, the change in each rat group was also examined for subgroup analysis. All three models were able to identify cerebral ischemic change and damage as IVIM parameter change among three phases. Furthermore, the kurtosis model could identify the parameter changes in more regions than the other two models. In the subgroup analysis with the kurtosis model, ADC in non-LS group significantly decreased between UCCAO and BCCAO but not in LS group. IVIM parameters at 11.7TMRI may help us to detect the subtle ischemic change; in particular, with the kurtosis model.

Expression of mucosal addressin cell adhesion molecule-1 on the reticular framework between white pulp and the marginal zone in the human spleen.

The antigenic heterogeneity of the reticular framework of the white pulp and marginal zone is well documented in the human adult spleen. Immunostaining of α-smooth muscle actin characterizes the heterogeneity of the reticular framework of the white pulp and marginal zone. In the human spleen, the blood cells flow in an open circulation. T and B lymphocytes flow out from the arterial terminal, and migrate in the reticular framework. Homing of lymphocytes to lymphoid tissues is regulated by selective interactions between cell surface homing receptors and tissue vascular addressins at sites of lymphocyte recruitment from the blood. In the present study, mucosal addressin cell adhesion molecule-1 was selectively expressed on α-smooth muscle actin-positive reticular framework. The reticular framework may function in lymphocyte homing and segregation into the periarteriolar lymphoid sheath, lymph follicle and marginal zone.

Fluvastatin exerts an antitumor effect in vemurafenib-resistant melanoma cells.

Although vemurafenib has been shown to improve the overall survival of patients with metastatic melanoma harboring the BRAF V600E mutation, its efficacy is often hampered by drug resistance acquired within a relatively short period through several distinct mechanisms. In the present study, we investigated the effect of fluvastatin as a possible strategy to overcome such acquired resistance using a cultured cell line model. We established vemurafenib-resistant (VR) cells from three BRAF (V600E)-mutated melanoma lines (C32, HMY-1, and SK-MEL-28) and evaluated the mechanism of acquired resistance of VR cells by water-soluble tetrazolium salts assay, western blot, real-time quantitative PCR, and immunofluorescent microscopy. The efficacy of the combination of growth inhibitory effect of vemurafenib and fluvastatin on respective parental and VR cells were assessed by calculating combination index and western blot. IC50 values of three VR cells were ~5-100-fold higher than those for the respective parental cells. The VR cells derived from HMY-1 and SK-MEL-28 showed constitutive activation of AKT kinase, and the specific AKT inhibitor MK-2208 or the PI3K inhibitor wortmannin increased the cellular sensitivity to vemurafenib. Intriguingly, application of a statin-related drug, fluvastatin, also resulted in a synergistic increase of sensitivity to vemurafenib in the VR cells (combination index: 0.73-0.86) probably by alleviating constitutive AKT activation, whereas the same treatment did not notably alter the vemurafenib sensitivity of the parental cells. Our results suggest the possible usefulness of statin-related drugs for overcoming vemurafenib resistance acquired through constitutive activation of the PI3K-AKT axis.

Correction: Involvement of C-terminal truncation mutation of kinesin-5 in resistance to kinesin-5 inhibitor.

[This corrects the article DOI: 10.1371/journal.pone.0209296.].

Involvement of C-terminal truncation mutation of kinesin-5 in resistance to kinesin-5 inhibitor.

Cultured cells easily develop resistance to kinesin-5 inhibitors (K5Is) often by overexpressing a related motor protein, kinesin-12/KIF15, or by acquiring mutations in the N-terminal motor domain of kinesin-5/KIF11 itself. We aimed to identify novel mechanisms responsible for resistance to S-trityl L-cysteine (STLC), one of the K5Is, using human osteosarcoma cell lines. Among six lines examined, U-2OS and HOS survived chronic STLC treatment and gave rise to resistant cells with IC50s at least 10-fold higher than those of the respective parental lines. Depletion of KIF15 largely eliminated the acquired K5I resistance in both cases, consistent with the proposed notion that KIF15 is indispensable for it. In contrast to the KIF11-independent property of the cells derived from HOS, those derived from U-2OS still required KIF11 for their growth and, intriguingly, expressed a C-terminal truncated variant of KIF11 resulting from a frame shift mutation (S1017fs). All of the isolated clones harbored the same mutation, suggesting its clonal expansion in the cell population due to the growth advantage during chronic STLC treatment. Transgenic expression of KIF11S1017fs in the parental U-2OS cells, as well as in HeLa cells, conferred a moderate but reproducible STLC resistance, probably owing to STLC-resistant localization of the mutant KIF11 on mitotic spindle. Our observations indicate that both KIF15 and the C-terminal-truncated KIF11 contributes to the STLC resistance of the U-2OS derived cells.