Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2947-2953 ◽  
Author(s):  
Y. Zhou ◽  
M.L. King

The mitochondrial cloud is a unique cell structure found in stage I Xenopus oocytes that plays a role in mitochondriogenesis and in the distribution of germ plasm to the vegetal pole. Xcat-2 RNA specifically localizes to the mitochondrial cloud and moves with it to the vegetal subcortex in stage II oocytes. Later, in the 4-cell embryo, it is found in a pattern identical to the germ plasm. Following microinjection into stage I oocytes, synthetic Xcat-2 RNAs localize to the mitochondrial cloud within 22 hours. Transcripts are stable over this time period with very little evidence of degradation. The Xcat-2 3′untranslated region was found to be both required and sufficient for mitochondrial cloud localization. Further deletion analysis narrowed this localization signal to a 250 nucleotide region at the proximal end of the 3′untranslated region. This region is different from, but overlaps with, a domain previously shown to be sufficient to direct Xcat-2 to the vegetal cortex in stage IV oocytes. Examination of early stage I oocytes reveals a time when Xcat-2 is uniformly distributed, arguing against vectorial nuclear export into the mitochondrial cloud. Analysis of localization at different time points does not suggest active transport to the mitochondrial cloud. We postulate that localization occurs by selective entrapment of Xcat-2 within the cloud by localized binding sites.

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.


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.


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.


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.


Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 201-208 ◽  
Author(s):  
C. Forristall ◽  
M. Pondel ◽  
L. Chen ◽  
M.L. King

In Xenopus, localization of a rare class of mRNAs during oogenesis is believed to initiate pattern formation in the early embryo. We have determined the pattern of RNA localization for one of these RNAs, Xcat-2, which encodes a putative RNA-binding protein related to Drosophila nanos (Mosquera, L., Forristall, C., Zhou, Y. and King, M. L. (1993) Development 117, 377–386). Xcat-2 is exclusively localized to the mitochondrial cloud in stage I oocytes, moves with this body into the vegetal cortex during stage II and, later, partitions into islands consistent with it being a component of the germ plasm. As previously shown, Vg1 is not localized to the vegetal cortex until stage IV and distributes to all vegetal blastomeres during development. We found a direct correlation between the localized condition of these RNAs and their recovery in a detergent-insoluble fraction. We present evidence suggesting that differential RNA binding to a cytoskeletal component(s) in the vegetal cortex determines the pattern of inheritance for that RNA in the embryo.


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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9068-9068
Author(s):  
L. Goyal ◽  
S. Banavali ◽  
R. Bhagwat ◽  
B. Arora ◽  
M. Muckaden ◽  
...  

9068 Background: One the main reasons for delayed presentation of children with RB in India is non acceptance of enucleation. CT is being increasingly utilized as primary treatment of RB to reduce the tumor volume and thus avoid enucleation and/or external beam radiation (EBRT) in early stage disease and reduce the risk of relapse in advanced stage disease. Methods: This retrospective (from 1996 to 2001) study involved 62 Patients (pts) (30 were bilateral) who received CT consisting of monthly cycles of carboplatin, etoposide, vincristine and cyclophosphomide. Pts with stage I disease, were started on CT alone, whereas most of the other pts were also started on concurrent EBRT (50Gy). Where indicated, pts also received local therapy, usually cryotherapy & EBRT. Eyes which did not show response or had stable disease, were advised enucleation. Results: Majority of pts had Reese-Ellsworth groups IV-V (74.1%). 17 pts had Stg I, 22 Stg II, 17 Stg III & 6 Stg IV disease (St Jude’s). All pts received CT (median 12 cycles). Out of 92 eyes only 79 were evaluable (13 were already enucleated).The response rate was 73.2% (51.8% CR or near CR); 12.9% had progressive disease. 47 Pts (74%) received RT. Only 23 pts received focal treatment (Cryotherapy 15, laser 3, combination 5). Vision was present in 38 eyes (48.1%) at presentation. 26 eyes (68.4%) were finally saved with useful vision. 20 pts had recurrence. 18 have died (17 died of disease, 1 treatment related sepsis). In those following up in the clinic, survival is 77% for stage I; 78.5% for stage II; 41.6% for stage III. All stage IV pts have died except 1 with nodal disease. Conclusions: CT has a role in the management of RB, however unless it is coupled with good focal therapy the results are poor as shown here. Also longer follow-ups are required because of late recurrences. This data highlights that in developing countries the social reasons complicate patient treatment & compliance. Further efforts are needed to spread awareness of this disease so that patients are diagnosed and treated in earlier stages so as to improve the outcomes. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16523-e16523
Author(s):  
Hamid R. Mirshahidi ◽  
Elvin Hernandez ◽  
Matthew Ta ◽  
Sheley M Baylon ◽  
Minh Thy Pham ◽  
...  

e16523 Background: Multidisciplinary focused-care teams have shown beneficial outcomes in diagnosis and treatment in cancer patients as well as assist in providing accessible, cohesive and continuous care. The multidisciplinary team specializing in thoracic cancer at our institution includes thoracic surgeons, pulmonologists, medical oncologists, radiation oncologists, pathologists, radiologists and a weekly tumor board with the inclusion of a dietician, a pharmacist, and a psych/social worker. This study examined the effectiveness of a multidisciplinary focused program in improving overall care in lung cancer patients. Methods: Lung cancer patient data between January 2000-December 2009 were abstracted from the institutional cancer registry. Patient demographics, treatment received, and survival (1-year and 2-year) were compared between Group A (January 2000-July 2005) and Group B (August 2005-December 2009) using Fisher’s exact test. Results: 1202 patients (Group A = 760; Group B = 442) were evaluated. Majority of patients were > 60 years old, male, and has stage IV adenocarcinoma. Missing stage was less in Group B (13.8% vs 17.4%). Early stage patients in Group B received more surgeries and less inappropriate treatments. More palliative chemotherapy/radiation treatments were given in Group B late stage disease. More stage II (21.1% vs 2.3%) and IIIA (12% vs 1.5%) patients in Group B were treated with wedge resection and chemotherapy. One-year survival differences were seen between 2 groups in stage I, IIIA, and IV (P <0.05). 2-year survival difference was seen in stage IV disease (P<0.05). Conclusions: Introduction of multidisciplinary lung care team between 2005-2009 was associated with an increased patients being staged and more appropriate treatments. One year survival almost doubled in stage I patients where stage IV pts experienced up to 4 times improvement in 1- and 2-year survival. The results of the present evaluation appear to confirm the value of a multidisciplinary approach to the management of patients with lung cancer.


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