A role for condensin-mediator interaction in mitotic chromosomal organization.

Eukaryotic genomes are organized by condensin into 3D chromosomal architectures suitable for chromosomal segregation during mitosis. However, molecular mechanisms underlying the condensin-mediated chromosomal organization remain largely unclear. Here, we investigate the role of newly identified interaction between the Cnd1 condensin and Pmc4 mediator subunits in fission yeast, Schizosaccharomyces pombe. We develop a condensin mutation, cnd1-K658E, that impairs the condensin-mediator interaction and find that this mutation diminishes condensinmediated chromatin domains during mitosis and causes chromosomal segregation defects. The condensin-mediator interaction is involved in recruiting condensin to highly transcribed genes and mitotically activated genes, the latter of which demarcate condensin-mediated domains. Furthermore, this study predicts that mediator-driven transcription of mitotically activated genes contributes to forming domain boundaries via phase separation. This study provides a novel insight into how genome-wide gene expression during mitosis is transformed into the functional chromosomal architecture suitable for chromosomal segregation.

Non-contrast-enhanced breast MRI for evaluation of tumor volume change after neoadjuvant chemotherapy.

PURPOSE: Three-dimensional contrast-enhanced magnetic resonance imaging (3D-Ce-MRI) is a most powerful tool for evaluation of neoadjuvant chemotherapy (NAC). However, the use of contrast agent is invasive, expensive, and time consuming, Thus, contrast agent-free imaging is preferable. We aimed to investigate the tumor volume change after NAC using maximum intensity projection diffusion-weighted image (MIP-DWI) and 3D-Ce-MRI. METHOD: We finally enrolled 55 breast cancer patients who underwent NAC in 2018. All MRI analyses were performed using SYNAPSE VINCENT® medical imaging system (Fujifilm Medical, Tokyo, Japan). We evaluated the tumor volumes before, during, and after NAC. Tumor volume before NAC on 3D-Ce-MRI was termed Pre-CE and those during and after NAC were termed Post-CE. The observer raised the lower end of the window width until the tumor was clearly visible and then manually deleted the non-tumor tissues. A month thereafter, the same observer who was blinded to the 3D-Ce-MRI results randomly evaluated the tumor volumes (Pre-DWI and Post-DWI) using MIP-DWI with the same method. Tumor volume change between ΔCE (Pre-CE - Post-CE/Pre-CE) and ΔDWI (Pre-DWI - Post-DWI/Pre-DWI) and the processing time for both methods (Time-DWI and Time-CE) were compared. RESULTS: We enrolled 55 patients. Spearman's rho between ΔDWI and ΔCE for pure mass lesions, and non-mass enhancement (NME) was 0.89 (p < 0.01), 0.63(p < 0.01) respectively. Time-DWI was significantly shorter than Time-CE (41.3 ± 21.2 and 199.5 ± 98.3 respectively, p < 0.01). CONCLUSIONS: Non-contrast-enhanced Breast MRI enables appropriate and faster evaluation of tumor volume change after NAC than 3D-Ce-MRI especially for mass lesions.

Large Plaque-type Blue Nevus with GNAQ Q209P Mutation, Involving Mammary Gland Tissue: Under-Recognized Mammary Condition as an Origin of Primary Mammary Melanocytic Tumors.

ABSTRACT: Plaque-type blue nevus is a rare variant of blue nevi that was first described in 1954. This article presents clinical, macroscopic, histopathological, and genetic findings for a case of large plaque-type blue nevus expanding into the mammary gland tissue as well as the skin of the right breast. A 63-year-old woman presented with a congenital, large, blue-colored macule limited to the hypochondriac area of the right breast. A nodule 8 mm in diameter was also present in the mammary gland tissue. Magnetic resonance imaging was unable to detect diffuse melanin deposition in the mammary gland tissue, but pigmentation in the whole mammary parenchyma was observed in the cut surfaces of the mastectomy specimen. Histopathology revealed a sparse distribution of dendritic melanocytes in whole sections of the mammary fibrous tissue and partial sections of the dermis. The histopathological criteria for atypical cellular blue nevus were fulfilled for the mammary tumor. Nodal blue nevus was diagnosed in the sentinel lymph node. Sanger sequencing confirmed the GNAQ Q209P mutation, which was also identified in all 4 literature cases of plaque-type blue nevus, but rarely in conventional blue nevi and uveal melanoma. It should be noted that plaque-type blue nevus can expand into the mammary gland tissue, even if the pigmented lesion does not exist on the overlying breast skin. The mammary condition can be the origin of primary mammary melanocytic tumors. Mosaicism of the GNAQ Q209P mutation can be a characteristic genetic alteration to extensive blue nevi, including plaque-type blue nevus.

Can breast MRI and adjunctive Doppler ultrasound improve the accuracy of predicting pathological complete response after neoadjuvant chemotherapy?

BACKGROUND: To examine the accuracy of MRI and Doppler ultrasound (US) for detecting residual tumor after neoadjuvant chemotherapy (NAC) for breast cancer and evaluate whether adjunctive Doppler US improves the MRI accuracy. METHODS: We reviewed 276 invasive breast cancer cases treated with NAC. Tumors were classified into four subtypes based on estrogen receptor and HER2 status. Response to NAC was evaluated using contrast-enhanced MRI and Doppler US. Residual Doppler flow was assumed to indicate a residual tumor. MRI and Doppler findings were compared with the histopathological findings of resected specimens. Pathological complete response (pCR) was defined as neither in situ nor invasive cancer left. RESULTS: Of the 276 tumors, imaging complete responses were observed using MRI and Doppler US in 62 (22%) and 111 (40%), respectively, whereas pCR was achieved in 44 (16%). MRI and Doppler US predicted residual tumor with 88% and 69% sensitivity, 80% and 91% specificity, 87% and 73% accuracy, 96% and 98% PPV, and 56% and 36% NPV, respectively. The accuracies of MRI and Doppler US were significantly higher for HER2-negative than HER2-positive tumors (p < 0.001 and p = 0.043, respectively). Seven (26%) of 27 false-negative cases identified by MRI were correctly diagnosed as positives with adjunctive Doppler US. CONCLUSIONS: Although MRI accurately detected residual tumor with 87% accuracy, this was still not sufficient to meet clinical demands and differed with tumor subtype. Adjunctive Doppler US in cases that appear to show a complete response on MRI might reduce chances of false negatives and increase the NPV of MRI for predicting residual tumor.

Evaluation of Breast Edema Findings at T2-weighted Breast MRI Is Useful for Diagnosing Occult Inflammatory Breast Cancer and Can Predict Prognosis after Neoadjuvant Chemotherapy.

Background Prediction of occult inflammatory breast cancer (IBC) and breast cancer prognosis based on breast edema findings on T2-weighted MRI scans, even for patients without clinical signs of IBC, would be useful in both pretreatment planning and prognosis and may elucidate the underlying biologic mechanisms. Purpose To evaluate whether classification of breast edema on T2-weighted MRI scans is useful for predicting the prognosis of patients with breast cancer treated with neoadjuvant chemotherapy (NAC). Materials and Methods A retrospective evaluation was performed of women with breast cancer who underwent breast MRI and were treated with NAC between January 2011 and December 2018. Breast edema on T2-weighted images was scored on a scale of 1 to 4, as follows: (a) breast edema score (BES) 1, no edema; (b) BES 2, peritumoral edema; (c) BES 3, prepectoral edema; and (d) BES 4, subcutaneous edema (suspicious for occult IBC). Clinically evident IBC was classified as BES 5 (without MRI). The log-rank test was performed, and hazard ratios were calculated using the Cox hazard model to evaluate associations between BES and progression-free survival (PFS) and overall survival (OS). PFS rate at 100 months after initiation of therapy was also evaluated. Results Of 408 patients (median age, 53 years; range, 28-80 years), 65 (16%) had a recurrence and 27 (7%) died. The log-rank test revealed differences in PFS for BES 4 versus 1, BES 5 versus 1, BES 5 versus 2, and BES 5 versus 3 (adjusted P < .05 for all). PFS rates for BES 1-5 were 0.92, 0.85, 0.80, 0.62, and 0.58, respectively, and the corresponding OS rates at 100 months were 0.98, 0.91, 0.92, 0.77, 0.86, respectively. Conclusion Classification of breast edema findings on T2-weighted MRI scans using a breast edema score was related to the prognosis of patients after neoadjuvant chemotherapy. © RSNA, 2021 Online supplemental material is available for this article.

Is the presence of edema and necrosis on T2WI pretreatment breast MRI the key to predict pCR of triple negative breast cancer?

PURPOSE: Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. METHOD: We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. RESULTS: Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. CONCLUSIONS: In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. KEY POINTS: • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

Probabilistic exposure assessment of aggregate rates of dermal exposure of Japanese women and children to parabens in personal care products.

Parabens (p-hydroxybenzoic acids) are commonly used as preservatives in personal care products. Although the rate of exposure to a single product may be small, it is possible for an individual to have marked exposure to parabens through the use of multiple personal care products (aggregate exposure). To assess the risks associated with aggregate exposure to parabens, we estimated the dermal exposure rate distributions of four major parabens (methylparaben, MP; ethylparaben, EP; propylparaben, PP; butylparaben, BP) in various products for women (>20 years old) and children (1-3 years old) by using the probabilistic exposure assessment tool ConsExpo. Integrated exposure rates were then calculated as the sum of exposure rates for individual products. Aggregate exposure rates for women were 1.2 (median) (0.13 [5%ile], 6.9 [95%ile]), 0.43 (0.029, 3.0), 0.35 (0.032, 1.9), and 0.25 (0.027, 1.2) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Those for children were 0.47 (0.054, 2.2), 0.11 (0.012, 0.60), 0.13 (0.012, 0.78), and 0.13 (0.0065, 0.85) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Integrated exposure rates for women were several times those for children. In both cases, personal care products that were applied to larger areas of skin and were used more frequently were more likely to be associated with higher exposure rates. According to the results of a risk assessment using a margin of exposure approach, aggregate rates of exposure to PP and BP, but not MP or EP, were high enough to warrant concern about disruption of the reproductive system.

Imaging features of breast cancer with marked hemosiderin deposition: A case report.

A 63-year-old woman was referred to our hospital for breast cancer treatment. She had a large HER2-positive breast tumor on her left breast, and received neoadjuvant chemotherapy. After treatment, a shrunk spiculated mass with calcification-like high density was detected on mammography, and MRI revealed a large strong susceptibility artifact. Surgical specimen analysis attributed these imaging features to a large marked hemosiderin deposition. This case is herein reported due to its rarity and to the importance of acknowledging that this large marked hemosiderin depositions can present as a calcification-like high density on mammography and shows large susceptibility artifact on MRI imaging.

MRI-detected breast lesions: clinical implications and evaluation based on MRI/ultrasonography fusion technology.

Magnetic resonance imaging (MRI) is a highly sensitive imaging modality that frequently reveals additional breast lesions that are occult on mammography and ultrasonography (US) and are thus difficult to diagnose. It is important to investigate these MRI-detected suspicious lesions, which are associated with a fairly high rate of malignancy. In this review, we have discussed MRI/US fusion technology, a magnetic position tracking system that synchronizes real-time US and MRI to improve lesion detection and enables comparisons of MRI and US findings of the detected lesions. This combination increases the precision of second-look US. We hope that our review underscores the importance of understanding the US findings and histopathology of MRI-detected breast lesions, as this will enable radiologists to perform appropriate assessments.

Does breast cancer growth rate really depend on tumor subtype? Measurement of tumor doubling time using serial ultrasonography between diagnosis and surgery.

BACKGROUND: Breast cancer growth is generally expected to differ between tumor subtypes. We aimed to evaluate tumor doubling time (DT) using ultrasonography and verify whether each tumor subtype has a unique DT. METHODS: This retrospective study included 265 patients with invasive breast cancer who received serial ultrasonography between diagnosis and surgery. Tumor diameters were measured in three directions and DTs were calculated according to an exponential growth model using the volume change during serial ultrasonography. We investigated the relationships between DT, tumor subtype, and histopathological factors. RESULTS: Volumes did not change in 95 (36%) of 265 tumors and increased in 170 (64%) tumors during serial ultrasonography (mean interval, 56.9 days). The mean volume increases of all tumors and volume-increased tumors were 22.1% and 34.5%, respectively. Triple-negative tumors had greater volume increases (40% vs. 20%, p = 0.001) and shorter DT (124 vs. 185 days, p = 0.027) than estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- tumors. Volume-increased tumors had higher Ki-67 indices than those of volume-stable tumors in ER+/HER2- (p = 0.002) and ER+/HER2+ tumors (p = 0.011) and higher histological grades in all tumors except triple-negative tumors (p < 0.001). Triple-negative tumors with DTs < 90 days (short-DT) showed higher Ki-67 indices than those with DTs > 90 days (long-DT) (p = 0.008). In ER+/HER2- tumors, histological grades were higher for short-DT than for long-DT tumors (p = 0.022). CONCLUSION: Differences in tumor DT depending on breast cancer subtype, Ki-67 index, and histological grade were confirmed using serial ultrasonography even during preoperative short interval.

T2-hypointense rim of breast mass lesions on magnetic resonance images: Radiologic-pathologic correlation.

We investigated the radiologic-pathologic correlation of a strong hypointense rim on T2-weighted images (T2-hypo-rim) surrounding breast mass lesions and evaluated its clinical significance. We retrospectively reviewed 3503 consecutive breast magnetic resonance imaging (MRI) examinations. The T2-hypo-rim was defined as a border of strong hypointensity compared with the fat signal on fat-suppressed T2-weighted images. Detected lesions with T2-hypo-rim were classified as a solid or cystic mass with MRI and correlated with histopathologic findings. Sixty-two masses (2%; 34 solid, 28 cystic) with T2-hypo-rim were detected [44 breast cancers, 18 benign lesions, including 15 (24%) papillary tumors]. Patients with cancer were significantly older than those with benign lesions (P = .002). Breast cancers were significantly larger than benign masses (P = .023). In 49 of 62 lesions (24 solid and 16 cystic cancers; three solid and six cystic benign masses), the rims were accurately correlated with the histopathologic findings. All malignant and benign cystic masses exhibited hemosiderin deposits in the cyst walls. However, 22 of 24 solid cancers and no solid benign masses exhibited hemosiderin at the tumor periphery (92% and 0%, respectively, P < .001). In addition, a thick fibrous capsule was present in nine (38%) of 24 solid cancers and none of the solid benign lesions. Strong T2-hypo-rims mostly correlated with hemosiderin deposits and/or sometimes fibrous capsules. Although the rims could not distinguish malignant from benign cystic lesions, they indicated malignancy in solid mass lesions on MRI. Additionally, the rims often indicated papillary tumors.

Comparison of visibility of circumscribed masses on Digital Breast Tomosynthesis (DBT) and 2D mammography: are circumscribed masses better visualized and assured of being benign on DBT?

OBJECTIVE: To compare the visibility of circumscribed masses on digital breast tomosynthesis (DBT) images and 2D mammograms and determine the usefulness of DBT for differentiation between benign and malignant circumscribed masses. METHODS: Seventy-one (19 malignant and 52 benign) mammographic well-circumscribed masses were included. Visibility of the masses and halo signs on DBT images were retrospectively compared with 2D mammograms. The effects of mammographic breast density on mass visibility were also evaluated. RESULTS: For DBT, 83% were superior and 17% were equivalent in visibility of the masses to that of 2D, and superiority of DBT was significantly enhanced in the high breast density group compared with the low breast density group (91% vs 68%, respectively, p = 0.016). Three lesions were only detected on DBT. There was no significant difference in the superiority of DBT for lesion visibility between malignant and benign masses. The halo sign was detected in 58% lesions on DBT and in 4% on 2D (p < 0.001). CONCLUSION: Circumscribed masses were better visualized on DBT than on 2D mammograms, particularly in high-density breasts. The halo sign often appeared on DBT and gave a clearer mass margin. However, circumscribed masses on DBT are not assured of being benign. KEY POINTS: • Circumscribed masses were better visualized on breast tomosynthesis than on 2D mammography. • Tomosynthesis visualized circumscribed masses better than 2D for all breast density categories. • Halo signs often appeared on tomosynthesis and contributed to detect circumscribed margins. • Circumscribed masses on tomosynthesis images are not assured of being benign lesions.

CD133 Modulate HIF-1α Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells.

UNLABELLED: Although CD133 is a known representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia is not fully known. The aim of this study is to demonstrate that CD133 regulates hypoxia inducible factor (HIF)-1α expression with tumor migration. The CD133⁺ pancreatic cancer cell line, Capan1M9, was compared with the CD133(-) cell line, shCD133M9, under hypoxia. HIF-1α expression levels were compared by Western blot, HIF-1α nucleus translocation assay and real-time (RT)-PCR. The hypoxia responsive element (HRE) was observed by luciferase assay. The migration ability was analyzed by migration and wound healing assays. Epithelial mesenchymal transition (EMT) related genes were analyzed by real-time RT-PCR. HIF-1α was highly expressed in Capan1M9 compared to shCD133M9 under hypoxia because of the high activation of HRE. Furthermore, the migration ability of Capan1M9 was higher than that of shCD133M9 under hypoxia, suggesting higher expression of EMT related genes in Capan1M9 compared to shCD133M9. CONCLUSION: HIF-1α expression under hypoxia in CD133⁺ pancreatic cancer cells correlated with tumor cell migration through EMT gene expression. Understanding the function of CD133 in cancer aggressiveness provides a novel therapeutic approach to eradicate pancreatic cancer stem cells.

Real-time virtual sonography examination and biopsy for suspicious breast lesions identified on MRI alone.

OBJECTIVES: The purpose of our study was to assess whether there is a potential additional value of real-time virtual sonography (RVS) to second-look ultrasound (US) examination and biopsy for breast lesions identified on MRI alone. METHODS: A retrospective review of the records of 70 consecutive patients (78 lesions) with breast abnormalities identified on MRI alone was performed. All suspicious enhancing lesions were subsequently evaluated with second-look US. Lesions not observed on second-look US underwent RVS. Pathological findings were confirmed by subsequent percutaneous biopsy or excision. RESULTS: Of the 78 MRI-detected lesions, second-look US correlation was made in 50 (64 %), including 22 malignant and 28 benign lesions. The remaining 28 lesions (36 %) were scheduled to undergo RVS. Four lesions were not visible on the second breast MRI. The remaining 24 lesions were RVS correlated and underwent RVS-guided biopsy; these included seven malignant and 17 benign lesions. Overall, 74 of 74 (100 %) true MRI-detected lesions were confirmed by histological results without using MRI-guided breast biopsy. The cancer rate was 29 %. CONCLUSIONS: RVS can increase the sonographic detection and biopsy rate of lesions identified on breast MRI alone. KEY POINTS: • All 74 MRI-detected lesions were confirmed without using MRI-guided biopsy. • Four lesions were not visible on second breast MRI. • RVS can increase sonographic detection of lesions identified on breast MRI alone. • RVS-guided breast biopsy can be an alternative to MRI-guided biopsy.

A plausible mechanism, based upon Short-Root movement, for regulating the number of cortex cell layers in roots.

Formation of specialized cells and tissues at defined times and in specific positions is essential for the development of multicellular organisms. Often this developmental precision is achieved through intercellular signaling networks, which establish patterns of differential gene expression and ultimately the specification of distinct cell fates. Here we address the question of how the Short-root (SHR) proteins from Arabidopsis thaliana (AtSHR), Brachypodium distachyon (BdSHR), and Oryza sativa (OsSHR1 and OsSHR2) function in patterning the root ground tissue. We find that all of the SHR proteins function as mobile signals in A. thaliana and all of the SHR homologs physically interact with the AtSHR binding protein, Scarecow (SCR). Unlike AtSHR, movement of the SHR homologs was not limited to the endodermis. Instead, the SHR proteins moved multiple cell layers and determined the number of cortex, not endodermal, cell layers formed in the root. Our results in A. thaliana are consistent with a mechanism by which the regulated movement of the SHR transcription factor determines the number of cortex cell layers produced in the roots of B. distachyon and O. sativa. These data also provide a new model for ground tissue patterning in A. thaliana in which the ability to form a functional endodermis is spatially limited independently of SHR.

[Successful ventilator weaning by trastuzumab in a HER2-positive breast cancer patient with multiple lung metastases].

We report a case of breast cancer with severe respiratory dysfunction due to multiple lung metastases, which was recovered by treatment with weekly trastuzumab administration. A 47-year-old woman with breast cancer had received a folk remedy from a general practitioner for 4 years. However, she was delivered to a hospital because of severe dyspnea, and intubation was found to be needed and performed. She was diagnosed with left breast cancer with skin and pleural wall invasion, and multiple lung metastases. Pathological examination showed invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive. After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory function improved gradually, and ventilator weaning was successful at 53 days after trastuzumab administration. CT examination also showed a remarkable reduction of lung and lymph node metastases and pleural effusion. She was discharged from our hospital 80 days after treatment, and her treatment with trastuzumab and capecitabine has been ongoing at an outpatient clinic.

Clinical outcomes of laparoscopic surgery for transverse and descending colon cancers in a community setting.

INTRODUCTION: The feasibility, safety and oncological outcomes of laparoscopic surgery for transverse and descending colon cancers in a community hospital setting were evaluated. METHODS: Twenty-six patients with transverse or descending colon cancers who underwent laparoscopic surgery at our hospital were included in this retrospective analysis (group A). Their outcomes were compared with those of 71 patients who underwent laparoscopic surgery for colon cancer at other tumor sites (group B). RESULTS: There were no significant differences between the two groups in terms of operative time, estimated blood loss, postoperative hospital stay and morbidity rate. Extended lymphadenectomy was performed more frequently and the number of harvested lymph nodes was significantly higher in group B than in group A. However, no recurrence developed in group A, while recurrence occurred in four patients from group B. The 3-year disease-free survival rates were 100% for group A and 93.5% for group B. The 3-year overall survival rates were 100% for group A and 91.6% for group B. CONCLUSIONS: Laparoscopic surgery for transverse and descending colon cancers can be performed safely with oncological validity in a community hospital setting, provided there is careful selection of the patients and adequate lymphadenectomy considering the clinical stage of their disease.

Impact of adjuvant radiation therapy for microscopic residual tumor after resection of extrahepatic bile duct cancer.

OBJECTIVES: The effect of adjuvant radiation therapy (RT) in extrahepatic bile duct (EHBD) cancer patients with microscopic-positive resection margins (R1 resection) is still controversial. METHODS: Between January 2000 and March 2010, 52 patients with EHBD cancer underwent surgery at our institution, of whom 36 were subjected to a retrospective analysis. Eleven patients received adjuvant RT after resection [surgery (S)+RT group], which included 9 patients with R1 resection and 2 with para-aortic lymph node metastasis. Their oncological outcomes were analyzed and compared with those of the 25 patients with R0 resection who did not receive adjuvant RT (S group). RESULTS: Patients in the S+RT group had significantly more advanced disease than those in the S group. However, there was no significant difference in disease-free survival or overall survival between the 2 groups. Median survival times for the S+RT and the S groups were 44 and 47 months, respectively, whereas the 5-year survival rates were 38.9% and 46%, respectively (P=0.707). Locoregional recurrence was less frequent in the S+RT group as compared with the S group, but the incidence of distant metastasis was unaffected by the adjuvant RT. CONCLUSIONS: Our results support the beneficial effect of adjuvant RT in EHBD cancer patients with R1 resection. This effect seems to result from an improved control of the locoregional tumor by adjuvant RT.

SCARECROW reinforces SHORT-ROOT signaling and inhibits periclinal cell divisions in the ground tissue by maintaining SHR at high levels in the endodermis.

In contrast to development in animals, much of the patterning of plants occurs post-embryonically in specialized structures called meristems. The root apical meristem of Arabidopsis thaliana is a readily accessible structure that has been extensively studied to uncover the factors that control root growth and cellular patterning. Recently we showed that one of the key factors in patterning the root, the mobile transcription factor SHORT-ROOT (SHR), acts in a concentration-dependent manner to initiate or suppress asymmetric divisions in the endodermis. The amount of SHR varies dynamically in the endodermis with the age of the root. Here we show that this variation is controlled in part through the activity of the transcription factor, SCARECROW (SCR), which regulates SHR movement and therefore its effective concentration and function in the endodermis.

The SHORT-ROOT protein acts as a mobile, dose-dependent signal in patterning the ground tissue.

A key question in developmental biology is how cellular patterns are created and maintained. During the formation of the Arabidopsis root, the endodermis, middle cortex (MC), and cortex are produced by periclinal cell divisions that occur at different positions and at different times in root development. The endodermis and cortex arise continuously from the periclinal divisions of cells that surround the quiescent center (QC) at the tip of the root. The MC arises between days 7 and 14 from periclinal divisions of the endodermis. The divisions that produce the middle cortex begin in the basal region of the root meristem away from the QC and then spread apically and circumferentially around the root. Although the transcription factor SHORT-ROOT (SHR) is required for both of these divisions, the mechanism that determines where and when SHR acts to promote cell division along the longitudinal axis of the root is unknown; SHR is present along the entire length of the root tip, but only promotes periclinal divisions at specific sites. Here we show that the abundance of the SHR protein changes dynamically as the root develops, and that the pattern of cell division within the endodermis is sensitive to the dose of this protein: high levels of SHR prevent the formation of the MC, whereas intermediate levels of SHR promote MC formation. These results provide a mechanism for the longitudinal patterning of the endodermis, and represent the first example in plants of a mobile transcription factor whose function (activator or repressor) depends upon concentration.