Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase.

Animal cells undergo rapid rounding during mitosis, ensuring proper chromosome segregation, during which an outward rounding force abruptly increases upon prometaphase entry and is maintained at a constant level during metaphase. Initial cortical tension is generated by the actomyosin system to which both myosin motors and actin network architecture contribute. However, how cortical tension is maintained and its physiological significance remain unknown.

Enrichment of CLDN18-ARHGAP fusion gene in gastric cancers in young adults.

Gastric cancer in young adults has been pointed out to comprise a subgroup associated with distinctive clinicopathological features, including an equal gender distribution, advanced disease, and diffuse-type histology. Comprehensive molecular analyses of gastric cancers have led to molecular-based classifications and to specific and effective treatment options. The molecular traits of gastric cancers in young adults await investigations, which should provide a clue to explore therapeutic strategies.

Mitotic phosphorylation of HP1α regulates its cell cycle-dependent chromatin binding.

Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that plays a crucial role in heterochromatin-mediated gene silencing. We previously showed that mammalian HP1α is constitutively phosphorylated at its N-terminal serine residues by casein kinase II (CK2), and that this phosphorylation enhances HP1α's binding specificity for nucleosomes containing lysine 9-methylated histone H3 (H3K9me). Although the presence of additional HP1α phosphorylation during mitosis was reported more than a decade ago, its biological significance remains largely elusive.

A diagnostic strategy for breast calcifications based on a long-term follow-up of 615 lesions.

Purpose: To clarify the long-term outcomes of breast calcifications after stereotactic vacuum-assisted breast biopsy (SVAB) and to develop strategy after SVAB.

Methods: Subject comprised 594 patients with 615 calcifications who underwent SVAB. 371 (60.

Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situ of the breast.

Purpose: Ductal carcinoma in situ (DCIS)-preinvasive breast cancer-with lymph node metastasis can clinically be treated as different stages: occult invasive cancer with true metastasis (T1N1) or pure DCIS with iatrogenic dissemination (TisN0). In this retrospective cohort study, we aimed to elucidate the prognostic impact and possible pathogenesis of nodal metastasis in DCIS to improve clinical management.

Methods: Subjects were comprised of 427 patients with routine postoperative diagnosis of DCIS who underwent sentinel node (SN) biopsy using molecular whole-lymph-node analysis.

Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer.

The agonistic/antagonistic biocharacter of selective estrogen receptor modulators (SERMs) can have therapeutic advantages, particularly in the case of premenopausal breast cancers. Although the contradictory effects of these modulators have been studied in terms of crosstalk between the estrogen receptor α (ER) and coactivator dynamics and growth factor signaling, the molecular basis of these mechanisms is still obscure. We identify a series of regulatory mechanisms controlling cofactor dynamics on ER and SERM function, whose activities require F-box protein 22 (Fbxo22).

Cytological Findings of Gastrointestinal Stromal Tumor-Derived Bone Metastasis.

Objective: Procedures for diagnosing bone tumors should be rapid and minimally invasive. Thus, cytological examinations are more useful for such purposes than histological examinations. In order to identify cytomorphological findings that could be used to diagnose bone metastasis from gastrointestinal stromal tumors (GIST), previous cases were reviewed.

Spinal Metastasis of Well-Differentiated Liposarcoma Component in Retroperitoneal Dedifferentiated Liposarcoma Treated by Minimally Invasive Surgery.

Case: Generally, well-differentiated liposarcoma (WDL) has recurrence potential but lacks metastatic potential. We present a rare case of spinal metastasis of WDL component in retroperitoneal dedifferentiated liposarcoma (DDL) treated by tumor curettage and L1 laminectomy followed by percutaneous pedicle screw fixation. Histological examination showed metastasis of the WDL component of DDL.

α-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10.

Synovial sarcoma (SS) is a rare yet refractory soft-tissue sarcoma that predominantly affects young adults. We show in a mouse model that radioimmunotherapy (RIT) with an α-particle emitting anti-Frizzled homolog 10 (FZD10) antibody, synthesized using the α-emitter radionuclide astatine-211 ( At-OTSA101), suppresses the growth of SS xenografts more efficiently than the corresponding β-particle emitting anti-FZD10 antibody conjugated with the β-emitter yettrium-90 ( Y-OTSA101). In biodistribution analysis, At was increased in the SS xenografts but decreased in other tissues up to 1 day after injection as time proceeded, albeit with a relatively higher uptake in the stomach.

Nucleolar integrity during interphase supports faithful Cdk1 activation and mitotic entry.

The nucleolus is a dynamic nuclear body that has been demonstrated to disassemble at the onset of mitosis; the relationship between cell cycle progression and nucleolar integrity, however, remains poorly understood. We studied the role of nucleolar proteins in mitosis by performing a global analysis using small interfering RNAs specific to nucleolar proteins; we focused on nucleolar protein 11 (NOL11), with currently unknown mitotic functions. Depletion of NOL11 delayed entry into the mitotic phase owing to increased inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1) and aberrant accumulation of Wee1, a kinase that phosphorylates and inhibits Cdk1.

Dynamics of sister chromatids through the cell cycle: Together and apart.

When and how sister chromatid resolution occurs after DNA replication is a fundamental question. Stanyte et al. (2018.

Quantitative analyses of the metaphase-to-anaphase transition reveal differential kinetic regulation for securin and cyclin B1.

Separation of sister chromatids is a drastic and irreversible step in the cell cycle. The key biochemistry behind this event is the proteolysis mediated by the ubiquitin ligase called the anaphase promoting complex, or APC/C. Securin and cyclin B1 are the two established substrates for APC/C whose degradation releases separase and inactivates cyclin B1-dependent kinase 1 (cdk1), respectively, at the metaphase-to-anaphase transition.

Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A.

Bone metastatic lesions are classified as osteoblastic or osteolytic lesions. Prostate and breast cancer patients frequently exhibit osteoblastic-type and osteolytic-type bone metastasis, respectively. In metastatic lesions, tumor cells interact with many different cell types, including osteoblasts, osteoclasts, and mesenchymal stem cells, resulting in an osteoblastic or osteolytic phenotype.

Author Correction: Sister chromatid resolution is an intrinsic part of chromosome organization in prophase.

In the version of this Letter originally published, the authors omitted a citation of an early study demonstrating topoisomerase-II-dependent sister chromatid resolution. This reference has now been added to the reference list as reference number 28, and the relevant text has been amended as follows to include its citation: 'Resolution must reflect the removal of sister-sister contacts, and we show here that Topo-IIα-mediated release of DNA catenation plays a major role (Fig. 4), in agreement with previous findings, whereas, surprisingly, cohesin dissociation is not strictly required (Fig.

The early onset of peripheral neuropathy might be a robust predictor for time to treatment failure in patients with metastatic breast cancer receiving chemotherapy containing paclitaxel.

Background: Paclitaxel plays a central role in chemotherapy for breast cancer. Peripheral neuropathy, a well-known toxicity with paclitaxel, may be of interest in predicting the efficacy of paclitaxel therapy for patients with metastatic breast cancer. We performed a retrospective analysis assessing whether the early occurrence of peripheral neuropathy (EPN) was a predictive marker for better efficacy in patients with metastatic breast cancer receiving chemotherapy containing paclitaxel.

Inter-observer agreement among pathologists in grading the pathological response to neoadjuvant chemotherapy in breast cancer.

Background: The degree of pathological response to neoadjuvant chemotherapy (NAC) was correlated with the prognosis in breast cancer. There are few studies published on inter-observer variability in the assessment of pathological responses among pathologists.

Methods: We collected 64 surgically resected specimens from patients who had received NAC.

The 4D nucleome in Kraków - Prospects for an emerging field.

asbtract It may seem obvious that the structural complexity of the cell nucleus should be investigated by microscopy methods. However, the researchers' toolbox has been enriched enormously in recent years by ideas arriving from a number of fields unrelated to microscopy. The recent conference 4D Nucleome: The Cell Nucleus in Space and Time, which was held in Kraków in May 2017, was an opportunity to appreciate the growing number of conceptual approaches and newly emerging analytical techniques that are revolutionizing our understanding of the structure of chromatin and the nucleus.

First report of eribulin in combination with pertuzumab and trastuzumab for advanced HER2-positive breast cancer.

Background: The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients.

Methods: In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab.

Surgical excision without whole breast irradiation for complete resection of ductal carcinoma in situ identified using strict, unified criteria.

Background: The definition of complete resection of ductal carcinoma in situ (DCIS) is difficult to standardize because of the high variety of surgical breast conserving procedures, specimen handling, and pathological examinations. Using strictly controlled criteria in a single institute, the present study aimed to determine the ipsilateral breast cancer rate when radiotherapy is omitted following complete resection of DCIS.

Methods: We retrospectively examined 363 consecutive DCIS patients who underwent breast-conserving surgery, and of these, 125 (34.

Clinicopathological factors predicting early and late distant recurrence in estrogen receptor-positive, HER2-negative breast cancer.

Background: Most studies analyzing prognostic factors for late relapse have been performed in postmenopausal women who received tamoxifen or aromatase inhibitors as adjuvant endocrine therapy for estrogen receptor (ER)-positive breast cancer.

Methods: A total of 223 patients (108 premenopausal and 115 postmenopausal) with early distant recurrence and 149 patients (62 premenopausal and 87 postmenopausal) with late distant recurrence of ER-positive, HER2-negative breast cancer who were given their initial treatment between 2000 and 2004 were registered from nine institutions. For each late recurrence patient, approximately two matched control patients without relapse for more than 10 years were selected.

Risk factors for pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment: a single-institute analysis.

Background: After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet.

Methods: We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment.

Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A.

The chromokinesin KIF4A has been implicated in shaping mitotic chromosomes, but its functional relationship to condensin complexes remains controversial. Here, we found that, in mitosis, KIF4A associates with condensin I but not with condensin II. Mutational analyses indicated that the enrichment of condensin I to chromosomal axes depends on its association with KIF4A in a way that likely involves its motor activity.

Predictive Factors and Value of ypN+ after Neoadjuvant Chemotherapy in Clinically Lymph Node-Negative Breast Cancer.

Background: Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone.