scholarly journals Rapamycin inhibits cell proliferation in type I and type II endometrial carcinomas: A search for biomarkers of sensitivity to treatment

2010 ◽  
Vol 119 (3) ◽  
pp. 579-585 ◽  
Author(s):  
Victoria L. Bae-Jump ◽  
Chunxiao Zhou ◽  
John F. Boggess ◽  
Young E. Whang ◽  
Lisa Barroilhet ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Type I ◽  
Type Ii ◽  
Endometrial Carcinomas

scholarly journals Type II endometrial cancers: original research on a series

2017 ◽  
Vol 6 (6) ◽  
pp. 2306
Author(s):  
B. L. Nayak ◽  
Sujata Misra ◽  
Suryakant Jaysingh ◽  
S. K. Giri
Keyword(s):  
Clear Cell ◽  
Myometrial Invasion ◽  
Serous Carcinoma ◽  
Original Research ◽  
Clear Cell Adenocarcinoma ◽  
Type I ◽  
Type Ii ◽  
Clinicopathological Analysis ◽  
Hematoxylin And Eosin ◽  
Endometrial Carcinomas

Background: Endometrial carcinoma, which ranks 3rd in India amongst the gynecological malignancies, is of two histological types: I and II. These differ in molecular as well as in clinical and histopathological profiles. Type II is estrogen independent, nonendometrioid, with higher grade histologies, more aggressive and carries an adverse prognosis.Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens in the Dept of Gynaec-oncology, AHRCC, Cuttack from November 2009 to January 2015 were included in the study. All specimens were fixed in 10% neutral buffered formalin and paraffin embedded for histological examination with hematoxylin and eosin staining. The clinicopathological analysis of the cases of EC was done with an emphasis on morphology.Results: Of a total of 150 cases of EC reported, 20 cases were classified as type II EC (13.33%) as per histology. The age of the patients ranged from 36 to 73 years, with mean age is 61 years. In 11 cases (55%), the myometrial invasion was more than half. the histological type was a clear cell adenocarcinoma in 50% of the cases. All were treated with hysterectomy and chemotherapy.Conclusions: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal.

Methionine aminopeptidases type I and type II are essential to control cell proliferation

2005 ◽  
Vol 95 (6) ◽  
pp. 1191-1203 ◽  
Author(s):  
Sylvie G. Bernier ◽  
Nazbeh Taghizadeh ◽  
Charles D. Thompson ◽  
William F. Westlin ◽  
Gerhard Hannig
Keyword(s):  
Cell Proliferation ◽  
Control Cell ◽  
Type I ◽  
Type Ii ◽  
Methionine Aminopeptidases

scholarly journals IFNγ suppresses the expression of GFI1 and thereby inhibits Th2 cell proliferation

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260204
Author(s):  
Murshed H. Sarkar ◽  
Ryoji Yagi ◽  
Yukihiro Endo ◽  
Ryo Koyama-Nasu ◽  
Yangsong Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Immune Response ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Th2 Cells ◽  
Type I ◽  
Type Ii ◽  
Cycle Progression ◽  
Th2 Cell ◽  
Differentiation And Proliferation

While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully understood. We found that IFNγ decreases the expression of growth factor independent-1 transcriptional repressor (GFI1) in Th2 cells, resulting in the inhibition of Th2 cell proliferation. The deletion of the Gfi1 gene in Th2 cells results in the failure of their proliferation, accompanied by an impaired cell cycle progression. In contrast, the enforced expression of GFI1 restores the defective Th2 cell proliferation, even in the presence of IFNγ. These results demonstrate that GFI1 is a key molecule in the IFNγ-mediated inhibition of Th2 cell proliferation.

scholarly journals Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation in the immature mouse

2004 ◽  
pp. 511-520 ◽  
Author(s):  
R Puglisi ◽  
M Montanari ◽  
P Chiarella ◽  
M Stefanini ◽  
C Boitani
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Receptor Expression ◽  
Postnatal Life ◽  
Type I ◽  
Type Ii ◽  
Testicular Cell ◽  
Stimulatory Action ◽  
Paracrine Signalling ◽  
Receptor Complexes

AIM: The aim of this study was to determine the action of bone morphogenetic proteins (BMPs) on testicular cell proliferation during early postnatal life, a definite developmental time at which crucial changes in germ cell and Sertoli cell maturation occur. METHODS: We investigated the effect of BMP2 and BMP7, two factors which belong to the relatively distant decapentaplegic (DPP) and 60 A classes of the large BMP family, upon spermatogonial and Sertoli cell proliferation, and we examined the expression of activin/BMP type II and type I receptors. We used in vitro cultured testis fragments from 7-day-old mice, highly purified populations of somatic and germ cells and total testes from mice of different ages. Cell proliferation was assessed by BrdU labelling and [3H]-thymidine incorporation. Ribonuclease protection assays and Northern blotting were performed to analyse receptor expression. RESULTS AND CONCLUSIONS: We have demonstrated a stimulatory action of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation respectively. ActRIIB is the type II receptor expressed most in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in addition to ActRIIB. By contrast, the presence of ActRIIA was undetectable in either germ or somatic cells. The type I receptors ActRIA, ActRIB and BMPRIA were all found in both cell types, indicating that the observed effect of BMP2 and BMP7 on testicular cell proliferation may be mediated by a number of combinatorial interactions in the receptor complexes. These findings suggest that BMPs are involved in physiological paracrine signalling during the first wave of spermatogenesis.

Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development

2006 ◽  
Vol 291 (5) ◽  
pp. L1101-L1111 ◽  
Author(s):  
Min Yee ◽  
Peter F. Vitiello ◽  
Jason M. Roper ◽  
Rhonda J. Staversky ◽  
Terry W. Wright ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Lung Development ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Newborn Mice ◽  
Type I Cells ◽  
Type Ii Cell ◽  
I Cells

Type II epithelial cells are essential for lung development and remodeling, as they are precursors for type I cells and can produce vascular mitogens. Although type II cell proliferation takes place after hyperoxia, it is unclear why alveolar remodeling occurs normally in adults whereas it is permanently disrupted in newborns. Using a line of transgenic mice whose type II cells could be identified by their expression of enhanced green fluorescent protein and endogenous expression of surfactant proteins, we investigated the age-dependent effects of hyperoxia on type II cell proliferation and alveolar repair. In adult mice, type II cell proliferation was low during room air and hyperoxia exposure but increased during recovery in room air and then declined to control levels by day 7. Eight weeks later, type II cell number and alveolar compliance were indistinguishable from those in room air controls. In newborn mice, type II cell proliferation markedly increased between birth and postnatal day 7 before declining by postnatal day 14. Exposure to hyperoxia between postnatal days 1 and 4 inhibited type II cell proliferation, which resumed during recovery and was aberrantly elevated on postnatal day 14. Eight weeks later, recovered mice had 70% fewer type II cells and 30% increased lung compliance compared with control animals. Recovered mice also had higher levels of T1α, a protein expressed by type I cells, with minimal changes detected in genes expressed by vascular cells. These data suggest that perinatal hyperoxia adversely affects alveolar development by disrupting the proper timing of type II cell proliferation and differentiation into type I cells.

scholarly journals The NSD2 p.E1099K Mutation in Relapse Pediatric Acute Lymphoblastic Leukemia Is Linked to Mercaptopurine Resistance

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3962-3962
Author(s):  
Jason Saliba ◽  
Joanna Pierro ◽  
Nikki Ann Evensen ◽  
Anita Qualls ◽  
Natasha Belsky ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Cell Counting ◽  
Type I ◽  
Type Ii ◽  
Set Domain

Abstract Introduction: While the outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically, the prognosis for those who relapse remains poor. One of the most common alterations found at relapse is the p.E1099K missense change within the SET domain of NSD2, a histone methyltransferase that di-methylates histone 3 lysine 36 (H3K36). NSD2 has 3 isoforms, two of which, Type II (canonical) and REIIBP (C-terminal), contain the SET domain, and another, Type I (N-terminal), that does not. The p.E1099K mutation leads to increased enzymatic activity, but pathways leading to a clonal advantage are unknown in ALL. Methods: We used short hairpin RNAs (shRNAs) to target knockdown of two combinations of NSD2 isoforms: shI/II targets Types I and II, shII/RE targets Type II and REIIBP. Three different B-cell lines (Reh, 697, and KOPN-8) with 2 wildtype (WT) copies of NSD2 were stably transduced with shII/RE. Two B-Cell lines, RS4;11 and RCH-ACV, heterozygous for the NSD2 p.E1099K mutation, were transduced with shI/II and shII/RE. As a control, each B-cell line was stably transduced with a scrambled non-targeting (NT) shRNA. NSD2 knockdown was confirmed by Western Blots. Cell lines were treated for 5 days with chemotherapy agents commonly used in pediatric ALL treatments (mercaptopurine (MP), cytarabine, methotrexate, prednisone, and doxorubicin). Cytotoxicity was assessed by CellTiter- Glo® and significance between IC50s was determined by ANOVA and post hoc Tukey test. Cell proliferation was measured by cell counting with trypan blue. Cell cycle progression in RS4;11 lines was monitored with Edu staining and flow cytometry with and without exposure to MP. Results: Similar to previously reported results, knockdown of NSD2 in the 3 WT B-cell lines had no effect on cell proliferation. However, shI/II reduced growth by 40% in RS4;11 and 20% in RCH-ACV, while shII/RE decreased proliferation by 45% in RS4;11 and 55% in RCH-ACV when compared to their NT control. In RS4;11, both shI/II and shII/RE led to a similar 10% decrease in cells progressing through S phase compared to NT, which could be due to either a slower progression through cell cycle or less cells entering the cell cycle. Knockdown of NSD2 resulted in sensitivity to 6MP compared to NT in both RS4;11 and RCH-ACV lines. RS4;11 shII/RE had an IC50 3.2-fold more sensitive ( p<.01) and the RS4;11 shI/II IC50 was 1.25-fold more sensitive (NS) versus the NT control. Similarly, RCH-ACV shII/RE had an IC50 3.4-fold more sensitive (p<.01) and the RCH-ACV shI/II IC50 was 2.6-fold more sensitive (p<.01) compared to the NT control. No significant changes in drug sensitivity were noted for the 3 WT NSD2 knockdown B-cell lines compared to their NT controls. During a 120 hour exposure to MP, 34% more RS4;11 shII/RE cells were arrested in the G phase than NT controls, while 26% more RS4;11 shI/II cells were arrested in G phase relative to NT controls. This result indicates MP exposure leads to a reduced percentage of knockdown cells able to progress through the cell cycle. Overall, simultaneously reduced expression of Type II and REIIBP had a greater effect of on cell proliferation and MP response compared to the co-reduction of Types I and II NSD2 in the p.E1099K heterozygous cell lines. Conclusion: The p.E1099K mutation confers a growth advantage and resistance to MP, a cornerstone of ALL therapy. Concurrent reduction of Type II and REIIBP expression by shII/RE resulted in the largest impact on proliferation and MP sensitivity. Both of these isoforms include the SET domain containing the p.E1099K mutation, which indicates one or both isoforms could be responsible for changes in the chromatin state and other possible alterations that lead to a clonal advantage. Based on our findings, determining the mechanism of resistance to MP imparted by NSD2 p.E1099K is now a top priority. Disclosures No relevant conflicts of interest to declare.

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