XMAP230 is required for the assembly and organization of acetylated microtubules and spindles in Xenopus oocytes and eggs

1998 ◽  
Vol 111 (16) ◽  
pp. 2315-2327 ◽  
Author(s):  
B.J. Cha ◽  
B. Error ◽  
D.L. Gard

We used affinity-purified polyclonal antibodies to characterize the distribution and function of XMAP230, a heat-stable microtubule-associated protein isolated from Xenopus eggs, during oogenesis. Immunoblots revealed that XMAP230 was present throughout oogenesis and early development, but was most abundant in late stage oocytes, eggs, and early embryos. Immunofluorescence microscopy revealed that XMAP230 was associated with microtubules in oogonia, post-mitotic stage 0 oocytes, early stage I oocytes, and during stage IV-VI of oogenesis. However, staining of microtubules by anti-XMAP230 was not detectable during late stage I through stage III. In stage VI oocytes, anti-XMAP230 stained a large subset of microtubules that were also stained with monoclonal antibodies specific for acetylated (α)-tubulin. During oocyte maturation, XMAP230 was associated with the transient microtubule array that serves as the precursor of the first meiotic spindle, as well as both first and second meiotic spindles. The extensive array of cytoplasmic microtubules present throughout maturation was not detectably stained by anti-XMAP230. Microinjection of anti-XMAP230 locally disrupted the organization and acetylation of microtubules in stage VI oocytes, and reduced the re-acetylation of microtubules during recovery from cold-induced microtubule disassembly. Subsequent maturation of oocytes injected with anti-XMAP230 resulted in defects in the assembly of the transient microtubules array and first meiotic spindle. These observations suggest that XMAP230 is required for the stabilization and organization of cytoplasmic and spindle microtubules in Xenopus oocytes and eggs.

2018 ◽  
Vol 36 (28) ◽  
pp. 2887-2894 ◽  
Author(s):  
Linda D. Mellby ◽  
Andreas P. Nyberg ◽  
Julia S. Johansen ◽  
Christer Wingren ◽  
Børge G. Nordestgaard ◽  
...  

Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of < 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort. Patients and Methods The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC. Results Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96. Conclusion This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6501-6501
Author(s):  
Jade Zhou ◽  
Shelly Kane ◽  
Celia Ramsey ◽  
Melody Ann Akhondzadeh ◽  
Ananya Banerjee ◽  
...  

6501 Background: Effective cancer screening leads to a substantial increase in the detection of earlier stages of cancer, while decreasing the incidence of later stage cancer diagnoses. Timely screening programs are critical in reducing cancer-related mortality in both breast and colorectal cancer by detecting tumors at an early, curable stage. The COVID-19 pandemic resulted in the postponement or cancellation of many screening procedures, due to both patient fears of exposures within the healthcare system as well as the cancellation of some elective procedures. We sought to identify how the COVID-19 pandemic has impacted the incidence of early and late stage breast and colorectal cancer diagnoses at our institution. Methods: We examined staging for all patients presenting to UCSD at first presentation for a new diagnosis of malignancy or second opinion in 2019 and 2020. Treating clinicians determined the stage at presentation for all patients using an AJCC staging module (8th edition) in the electronic medical record (Epic). We compared stage distribution at presentation in 2019 vs 2020, both for cancers overall and for colorectal and breast cancer, because these cancers are frequently detected by screening. Results: Total numbers of new patient visits for malignancy were similar in 2019 and 2020 (1894 vs 1915 pts), and stage distribution for all cancer patients was similar (stage I 32% in 2019 vs 29% in 2020; stage IV 26% in both 2019 and 2020). For patients with breast cancer, we saw a lower number of patients presenting with stage I disease (64% in 2019 vs 51% in 2020) and a higher number presenting with stage IV (2% vs 6%). Similar findings were seen in colorectal cancer (stage I: 22% vs 16%; stage IV: 6% vs 18%). Conclusions: Since the COVID-19 pandemic, there has been an increase in incidence of late stage presentation of colorectal and breast cancer, corresponding with a decrease in early stage presentation of these cancers at our institution. Cancer screening is integral to cancer prevention and control, specifically in colorectal and breast cancers which are often detected by screening, and the disruption of screening services has had a significant impact on our patients. We plan to continue following these numbers closely, and will present data from the first half of 2021 as it becomes available.


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 145-145
Author(s):  
Catherine R. Fedorenko ◽  
Karma L. Kreizenbeck ◽  
Li Li ◽  
Laura Elizabeth Panattoni ◽  
Veena Shankaran ◽  
...  

145 Background: The COVID-19 pandemic disrupted medical care, including routine cancer screening for breast, colorectal, lung and cervical cancers. We aimed to investigate the impact of the pandemic on stage at diagnosis for cancer patients. Methods: Using data from the Washington State SEER records we compared AJCC stage for patients diagnosed with cancer in 2017-2019 to 2020 for two time periods, March to June (initial pandemic months) and July to December (later pandemic months). Patients were included if they were age 18+, diagnosed with a solid tumor, and not diagnosed at autopsy. Results: In the early phase of the pandemic, March – June 2020, there was a shift to cancers being diagnosed at a later stage compared to the same time period in 2017-2019 (Stage III: 13.5% to 14.9%, Stage IV: 16.2% to 19.7%). There was also a decrease in cancer diagnoses for cancers that are often detected through routine screening. As a percentage of all cancer diagnoses, both melanoma (13.2% to 9.8%) and colon cancer diagnoses (7.2% to. 6.7%) decreased during the early pandemic. In the later phase of the pandemic, July to December 2020, the stage at diagnosis showed an indication of returning to pre-pandemic levels with an increase in the proportion of early stage cancers (In situ: 16.6% to 19.3%, Stage I: 38.8% to 41.1%). Stage at diagnosis trends varied by tumor type. For colorectal cancer, the overall number of diagnoses decreased during the initial pandemic months. Stage I diagnoses decreased and Stage IV cancer diagnoses increased in both early and late stages of the pandemic. Conclusions: In Washington State, the COVID-19 pandemic had an impact on stage at diagnosis potentially caused by delays or interruptions in medical care. Additional studies are needed to understand how this shift in stage at diagnosis impacted treatment and outcomes for patients.


2013 ◽  
Vol 23 (9) ◽  
pp. 1635-1641 ◽  
Author(s):  
Vicky Makker ◽  
Sara J. Kravetz ◽  
Jacqueline Gallagher ◽  
Oana-Paula Orodel ◽  
Qin Zhou ◽  
...  

ObjectiveTo evaluate overall survival (OS) and progression-free survival (PFS) after adjuvant therapy in stage I to stage IV uterine carcinosarcoma with rhabdomyosarcoma differentiation.MethodsMemorial Sloan-Kettering Cancer Center medical records from 1990 to 2012 were reviewed. Patients who received chemotherapy with or without radiation therapy (RT), or RT alone, for completely resected stage I to stage IV uterine carcinosarcoma with rhabdomyosarcoma differentiation were included.ResultsOf 53 patients, International Federation of Gynecology and Obstetrics stage distribution was as follows: I, 13 (24.5%); II, 8 (15.1%); III, 13 (24.5%); and IV, 19 (35.9%). Forty-one (77.4%) of 53 patients received adjuvant chemotherapy, and 34% of the patients who received chemotherapy also received pelvic RT or intravaginal brachytherapy (IVRT). Twelve (22.6%) of the 53 patients received only pelvic RT with/without IVRT. Paclitaxel-carboplatin was the most commonly used adjuvant chemotherapy treatment. The median PFS for the entire cohort was 13.4 months (95% confidence interval [CI], 10.5–17.0). The median OS for the entire cohort was 23.0 months (95% CI, 16.9–34.3). The median PFS periods by stage were 15.9 months for stages I/II versus 11.2 months for stages III/IV (P= 0.012). Median OS was not reached in the early-stage cohort. The median OS for the late-stage cohort was 20.9 months (P= 0.004). The median PFS periods by treatment were 10.4 months for pelvic RT with/without IVRT group versus 13.1 months for chemotherapy with/without pelvic RT with/without IVRT group (P= 0.498). The median OS periods by treatment were 23.6 months for chemotherapy with/without pelvic RT with/without IVRT group versus 16.9 months for pelvic RT with/without IVRT group (P= 0.501).ConclusionThe results suggest that chemotherapy alone or in combination with RT is associated with longer PFS and OS compared to RT alone. Only the stage of disease significantly affected PFS and OS.


2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21154-e21154
Author(s):  
Margaret Pruitt ◽  
Rajesh Naidu Janapala ◽  
Faysal Haroun

e21154 Background: Lung cancer is the leading cause of cancer death and the most common non-acquired immune deficiency syndrome defining malignancy in people living with HIV (PLWH). Disparities in outcomes have been observed despite lung cancer mortality reportedly decreasing in the general population over the last decade due to lower rates of smoking and the advent of novel therapies. To better understand the current trend in lung cancer in PLWH, we explored demographic characteristics, comorbidities, and lung cancer pathology and molecular data in this population. Methods: A retrospective search of patient charts was conducted from 2004 to January 2021 using billing codes for HIV and primary lung cancer. Patients who had incorrect HIV or primary lung cancer diagnoses were excluded. Results: The search yielded 45 patients, of which 11 were excluded as described above: 66% were males, 82% African American, and 18% Caucasian. About two-thirds of patients were living in zip codes with predominantly low to medium household incomes. The median pack years of patients diagnosed with Stage I or II non-small cell lung cancer (NSCLC) was 40, Stage III or IV NSCLC was 20, early stage small cell lung cancer (SCLC) was 30, and late stage SCLC was 60. The median time between HIV and lung cancer diagnoses was 21.7 years for Stage I or II NSCLC, 17.1 years for Stage III or IV NSCLC, 15.2 for early stage SCLC, and 13.3 for late stage SCLC. Of 26 patients with viral load (VL) data, 21 (80.7%) had VL less than 500 when lung cancer was diagnosed. Of the 33 charts with available pathology data, there were 16 adenocarcinomas, 6 squamous carcinomas, 3 adenosquamous carcinomas, 1 large cell neuroendocrine cancer, 4 SCLCs, 1 mesothelioma, and 2 unspecified NSCLCs. Of 19 patients with a histologic grade, 11 had a high-grade tumor (57.9%). For the NSCLCs, 8 were Stage I (28.5%), 2 Stage II (7.1%), 8 Stage III (28.5%), 9 Stage IV (32.1%), and 1 with an unspecified stage. One SCLC was early stage and the remaining 3 were late stage. Five patients had brain metastasis. Molecular data or PDL-1 expression was available for 10 adenocarcinomas (62.5%), 1 adenosquamous (33%), 3 squamous carcinomas (50%), and the large cell neuroendocrine cancer. An EGFR mutation was detected in 2 cancers. ALK rearrangement was found in 1. Other mutations were detected. Two cancers were in each PDL1 expression category: < 1%, 1-50%, and > 50%. Conclusions: Our study suggests that PLWH with lung cancer continue to have high rates of smoking. Viral load was well controlled. A range in stages of lung cancer was observed including earlier stages. Although molecular data was limited, available EGFR and ALK gene alterations, and PD-L1 expression prevalence were on par with that of the general population. With advancements in lung cancer treatment, additional research is needed in the PLWH population to better understand and mitigate disparities.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 596 ◽  
Author(s):  
Jing Guo ◽  
Wei-Lei Yang ◽  
Daewoo Pak ◽  
Joseph Celestino ◽  
Karen H. Lu ◽  
...  

Early detection of ovarian cancer promises to reduce mortality. While serum CA125 can detect more than 60% of patients with early stage (I–II) disease, greater sensitivity might be observed with a panel of biomarkers. Ten protein antigens and 12 autoantibody biomarkers were measured in sera from 76 patients with early stage (I–II), 44 patients with late stage (III–IV) ovarian cancer and 200 healthy participants in the normal risk ovarian cancer screening study. A four-biomarker panel (CA125, osteopontin (OPN), macrophage inhibitory factor (MIF), and anti-IL-8 autoantibodies) detected 82% of early stage cancers compared to 65% with CA125 alone. In early stage subjects the area under the receiver operating characteristic curve (AUC) for the panel (0.985) was significantly greater (p < 0.001) than the AUC for CA125 alone (0.885). Assaying an independent validation set of sera from 71 early stage ovarian cancer patients, 45 late stage patients and 131 healthy women, AUC in early stage disease was improved from 0.947 with CA125 alone to 0.974 with the four-biomarker panel (p = 0.015). Consequently, OPN, MIF and IL-8 autoantibodies can be used in combination with CA125 to distinguish ovarian cancer patients from healthy controls with high sensitivity. Osteopontin appears to be a robust biomarker that deserves further evaluation in combination with CA125.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15056-15056
Author(s):  
S. Kilickap ◽  
O. Dizdar ◽  
H. Harputluoglu ◽  
S. Aksoy ◽  
S. Yalcin

15056 Background: Determination of patients (pts) with early stage disease who have a high risk for developing metastatic disease is crucial. We investigated the risk factors associated with metastases development in pts with operable gastric cancer. Patients and Methods: In this retrospective study, pts with stage I-III and non-metastatic stage IV gastric cancer diagnosed between 1990 and 2006 were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, were reviewed. Logistic regression methods were used to determine the risk factors for developing metastasis and to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: 184 pts (70% male, 30% female) were analyzed. The mean age ± standard deviation was 56.5±11.9. The mean age of female were higher than male (p=0.014). At the time of diagnosis, 13.6% of the pts had stage I, 19.0% had stage II, 53.3% had stage III, and 14.1% had non-metastatic stage IV disease. The tumors were distally localized in 80% of the cases. Median follow-up period was 35 months. During follow up, 51 pts developed metastases. Median time to metastases development was 14 months. Overall survival was shorter in pts who developed metastasis than those who did not. (20 months vs. not reached, respectively, p=0.002). In univariate analyses, stage (p=0.020), tumor localization (p=0.006), extracapsular lymphatic extension (ELE) (p<0.001), the number of metastatic lymph nodes (p=0.001), CEA level (p<0.001), lymphovascular invasion (LVI) (p=0.001), and perineural invasion (p=0.007) were associated with metastasis development. In multivariate analysis, elevated CEA levels (p=0.009; OR: 2.8; CI 95%: 1.29–6.19), LVI (p=0.041; OR: 2.2; CI 95%: 1.03–4.64) and ELE (p=0.029; OR: 2.3; CI 95%: 1.09–4.78) were associated with increased risk of metastasis development while distal localization (p=0.038; OR: 0.42; CI%: 0.18–0.95) was associated with decreased risk in pts with gastric cancer. Discussion: In pts with early stage or locally advanced gastric cancer, elevated CEA levels, LVI, proximal localization and ELE were associated with increased risk of developing metastasis. Aggressive treatment options and closer follow up should be considered for pts with these risk factors. No significant financial relationships to disclose.


2005 ◽  
Vol 15 (3) ◽  
pp. 432-437
Author(s):  
S. Pather ◽  
M. A. Quinn

The records of all patients with clear-cell ovarian cancer (CCC) who underwent complete surgical staging and chemotherapy between 1984 and 2001 were reviewed and 39 patients identified as suitable for study. The mean patient age was 56 years, and the stage distribution was as follows: stage I, 53%; stage II, 13%; stage III, 32%; and stage IV, 2%. One in three patients with stage I disease developed recurrent disease despite adjuvant chemotherapy. Seventy percent of tumors demonstrated a response to combination carboplatin and paclitaxel. Tumors which had either a partial response or failed to respond to first-line chemotherapy demonstrated no response to second-line nonplatinum chemotherapy. Endometriosis was identified in 31% of tumors, and 18% of patients developed deep venous thrombosis (DVT); however, neither endometriosis nor DVT was associated with a poorer outcome. CCC has a high recurrence rate in early-stage disease despite adjuvant treatment with cytotoxic chemotherapy. Advanced disease does respond to carboplatin and paclitaxel, which should be the chemotherapeutic regimen of choice. New second-line agents are urgently required.


1987 ◽  
Vol 18 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Judith L. Page ◽  
Donna Horn

The purpose of this study was to determine if developmentally delayed children demonstrate superior comprehension for restricted, syntactically incomplete as compared to reduced, syntactically complete forms. Ten developmentally delayed children at linguistic stage I (MLU 1.00–1.99) participated in this study. Five children were functioning within early stage I (MLU 1.00–1.49) and five children were within late stage I (MLU 1.50–1.99). Children were asked to manipulate objects in response to declarative telegraphic and adult utterances, some of which included nonsense or inverted forms. Results revealed that late stage I children demonstrated better comprehension than early stage I children for all utterance types. Additionally, late stage I children responded equally well to all noninverted utterance types, whereas early stage I children exhibited differential performance according to utterance type. Both groups of children exhibited significantly poorer performance on inverted forms. Results were interpreted with regard to several variables that may affect comprehension performance.


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