PSCA and Oct-4 Expression in the Benign and Malignant Lesions of Gallbladder: Implication for Carcinogenesis, Progression, and Prognosis of Gallbladder Adenocarcinoma

PSCA and Oct-4 have been thought as markers of cancer stem cells. Although overexpression of PSCA and Oct-4 in cancer has been reported, little is known about the clinical and pathological significance with PSCA and Oct-4 expression in gallbladder adenocarcinoma. In this study, overexpression of PSCA and Oct-4 was detected in gallbladder adenocarcinoma (54.6% and 55.6%). Less expression of PSCA and Oct-4 was detected in the pericancerous tissues (19.6% and 21.7%), gallbladder polyps (13.3% and 13.3%), and gallbladder epithelium with chronic cholecystitis (14.3% and 14.3%). The overexpression of PSCA and Oct-4 was significantly associated with differentiation, tumor mass, lymph node metastasis, invasion of gallbladder adenocarcinoma, and decreased overall survival. Our study suggested that overexpression of PSCA and Oct-4 might be closely related to the carcinogenesis, progression, metastasis, or invasive potential and prognosis of gallbladder carcinoma.

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SINGLE PORT LAPAROSCOPIC CHOLECYSTECTOMY IN HUE CENTRAL HOSPITAL

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2012.2.4 ◽

2012 ◽

pp. 25-30

Author(s):

Xuan Dong Pham ◽

Nhu Hiep Pham ◽

Huu Thien Ho ◽

Anh Vu Pham ◽

Hai Thanh Nguyen ◽

...

Keyword(s):

Laparoscopic Cholecystectomy ◽

Single Port ◽

Operating Time ◽

Chronic Cholecystitis ◽

Central Hospital ◽

Gallbladder Polyp ◽

Gallbladder Polyps ◽

Hospital Patients ◽

Wound Pain ◽

Initial Results

Purpose: Evaluating the initial results in applying single port laparoscopic cholecystectomy at Hue Central Hospital. Patients and methods: 29 gallbladder polyps, gallstones with symptoms of acute or chronic cholecystitis and surgeried by single port laparoscopic cholecystectomy at Hue Central Hospital from March 2011 to December 2011. Results: Male/female was 0.45/1. Age: 49.24 ± 16.43 (21-81), 40 to 60 years 54.6%. Cholecystitis: 75.9%, 17.3% gallbladder polyp, gallbladder adenomyomatosis 3.4%. Added 1 trocart because difficult dissection surgery 10.2%, bleeding 6.8% difficult to handle, added 2 trocart 3.4%. Bleeding intraoperative 10.3%. Operating time: 76.2 ± 33.5 minutes, hospital stay: 4 - 6 days 51.7%. Wound pain after 2 weeks of hospital discharge 6.9%, with no wound seromas and no wound infection. Conclusions: Single port laparoscopic cholecystestomy is safe, has fewer complications, can be done with experienced surgeons laparoscopic surgery. Keywords: Single port laparoscopic cholecystectomy, gallbladder ston Key words: Single port laparoscopic cholecystectomy, gallbladder stone

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Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽

10.3390/cancers13071674 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1674

Author(s):

Sara Tomei ◽

Ola Ibnaof ◽

Shilpa Ravindran ◽

Soldano Ferrone ◽

Cristina Maccalli

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Immune Responses ◽

Antigen Processing ◽

Aberrant Expression ◽

Immunological Profile ◽

Malignant Lesions ◽

Novel Therapeutic Strategies ◽

Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

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Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽

10.1038/s41388-021-01722-8 ◽

2021 ◽

Vol 40 (12) ◽

pp. 2296-2308

Author(s):

Mei Wang ◽

Xinxin Zhao ◽

Rong Qiu ◽

Zheng Gong ◽

Feng Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Cells ◽

Node Metastasis ◽

Signaling Activation

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

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Circulating Tumor Cells and Cancer Stem Cells: Clinical Implications in Nonmetastatic Breast Cancer

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s40856 ◽

2016 ◽

Vol 10 ◽

pp. BCBCR.S40856 ◽

Cited By ~ 2

Author(s):

M. Sayed ◽

A.M. Zahran ◽

M.S.F. Hassan ◽

D.O. Mohamed

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Overall Survival ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Disease Free Survival ◽

Free Survival ◽

The Third ◽

Disease Free

Purpose Despite the therapeutic advances, disease recurrence remains an ever-present threat to the health and well-being of breast cancer survivors. Assessment of circulating tumor cells (CTCs) and cancer stem cells (CSCs) during and after treatment may be of value in refining treatment. Methods Three 5 mL blood samples were taken from each patient: the first, at diagnosis; the second, after completion of neoadjuvant anthracyclin-based chemotherapy; and the third, a month after surgery and completion of adjuvant radiotherapy. The absolute numbers of CTCs were identified as CD45-cytokeratin+ cells. CTCs per 5 mL of blood were determined by recording all events in the whole suspension. CSCs were identified as cytokeratin+CD44+CD24-/CD45- cells. The CSCs were expressed as a percentage of CTCs. Results Univariate analysis identified the measurements of baseline CTCs and CSCs, taken after chemotherapy and one month after the cessation of radiotherapy, as prognostic factors for both four-year disease-free survival and four-year overall survival. Multivariable analysis identified the third measurement of CSCs, taken one month after the completion of radiotherapy, as the only independent prognostic factor for the four-year disease-free survival (P < 0.002, hazard ratio [HR] = 1.231, 95% CI 1.077–1.407). The initial CTC measurement was the one factor that reached significance on multivariate analysis (P < 0.03, HR 1.969, 95% CI 1.092–3.551) for the four-year overall survival. Correlation was higher between CTC and CSC counts at diagnosis ( r = 0.654, P < 0.001) than after chemotherapy ( r = 0.317, P < 0.03), because of the more rapid decrease in the mean CTC count with chemotherapy. Conclusion The CTC count could be suitable as one of the measures for monitoring response to chemotherapy, while persistence of CSC after cessation of the treatment of nonmetastatic breast cancer, except hormonal therapy when indicated, may be a reason to consider additional therapy in the future. These findings need confirmation in larger randomized trials.

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The evolving concept of cancer and metastasis stem cells

The Journal of Cell Biology ◽

10.1083/jcb.201202014 ◽

2012 ◽

Vol 198 (3) ◽

pp. 281-293 ◽

Cited By ~ 246

Author(s):

Irène Baccelli ◽

Andreas Trumpp

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cell ◽

Tumor Cell ◽

Dynamic Processes ◽

Cellular Composition ◽

Tumor Mass ◽

Tumor Relapse ◽

Cancerous Cells ◽

Heterogeneous Tumor

The cancer stem cell (CSC) concept, which arose more than a decade ago, proposed that tumor growth is sustained by a subpopulation of highly malignant cancerous cells. These cells, termed CSCs, comprise the top of the tumor cell hierarchy and have been isolated from many leukemias and solid tumors. Recent work has discovered that this hierarchy is embedded within a genetically heterogeneous tumor, in which various related but distinct subclones compete within the tumor mass. Thus, genetically distinct CSCs exist on top of each subclone, revealing a highly complex cellular composition of tumors. The CSC concept has therefore evolved to better model the complex and highly dynamic processes of tumorigenesis, tumor relapse, and metastasis.

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Long-Term Survival in Patients With Para-Aortic Lymph Node Metastasis With Systematic Retroperitoneal Lymphadenectomy Followed by Adjuvant Chemotherapy in Endometrial Carcinoma

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181d80aff ◽

2010 ◽

Vol 20 (6) ◽

pp. 1000-1005 ◽

Cited By ~ 11

Author(s):

Masamichi Hiura ◽

Takayoshi Nogawa ◽

Takashi Matsumoto ◽

Takashi Yokoyama ◽

Yuko Shiroyama ◽

...

Keyword(s):

Overall Survival ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Lymph Node Metastasis ◽

Endometrial Carcinoma ◽

Peritoneal Cytology ◽

Term Survival ◽

Long Term Survival ◽

Node Metastasis

Objective:The purposes of this study were to assess modified radical hysterectomy including systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node (PAN) metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for long-term survival during the past 10 years.Methods:Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy and peritoneal cytology in 284 endometrial carcinoma patients according to the classification of the International Federation of Gynecology and Obstetrics (stage IA, n = 66; stage IB, n = 96; stage IC, n = 33; stage IIA, n = 5; stage IIB, n = 20; stage IIIA, n = 28; stage IIIC, n = 28; and stage IV, n = 8) who gave informed consents at our institute. Patients with tumor confined to the uterus (stages IC and II) were treated by 3 courses of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, and cisplatin 75 mg/m2 regimen 3 to 4 weeks apart, and patients with extrauterine lesions involving adnexa and/or pelvic lymph node (PLN) were treated by 5 courses. In addition, 10 courses were given to patients with PAN metastasis. Patients with PLN metastasis received adjuvant chemotherapy, and adjuvant radiation was not part of our institutional protocol. For multivariate regression modeling with proportional hazards, the regression model of Cox was used. Survival curves were analyzed by the Kaplan-Meier method, and analysis of the differences was performed by the log-rank test.Results:The overall incidence of retroperitoneal lymph node metastasis assessed by systematic pelvic and para-aortic lymphadenectomy was 12.0% (34/284) in stages I to IV endometrial carcinoma, and incidences of PLN and PAN metastases were 9.2% (26/284) and 7.4% (21/284), respectively. However, PAN metastasis rate is 50% (13/26) in patients with PLN metastasis. Univariate analysis of prognostic factors revealed that International Federation of Gynecology and Obstetrics clinical stage (P < 0.0001), histological finding (P = 0.0292), myometrial invasion (P < 0.0001), adnexal metastasis (P < 0.0001), lymphovascular space invasion (P < 0.0001), tumor diameter (P = 0.0108), peritoneal cytology (P = 0.0001), and retroperitoneal lymph node metastasis (P < 0.0001) were significantly associated with 10-year overall survival. Survival was not associated with age (P = 0.1558) or cervical involvement (P = 0.1828). A multivariate analysis showed that adnexal metastasis (P = 0.0418) and lymphovascular space invasion (P = 0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year overall survival rates in patients with negative PAN were 96% and 93% versus 72% and 62% in patients with positive PAN (P = 0.006).Conclusions:It is suggested that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy could improve long-term survival in patients with PAN metastasis, although there are only 21 patients with PAN metastasis.

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P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

Neuro-Oncology ◽

10.1093/neuonc/noab180.170 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii49-ii49

Author(s):

T Kazda ◽

R Lakomy ◽

I Selingerova ◽

P Pospisil ◽

L Hynkova ◽

...

Keyword(s):

Stem Cells ◽

Overall Survival ◽

Neural Stem Cells ◽

Spatial Relationship ◽

Clinical Biomarkers ◽

Increased Risk ◽

Initial Location ◽

Early Progression ◽

Multifocal Tumor ◽

Relationship Of

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or >25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p<0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.

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Tumor-infiltrating regulatory T cells, CD8/Treg ratio, and cancer stem cells are correlated with lymph node metastasis in patients with early breast cancer

Breast Cancer ◽

10.1007/s12282-020-01079-y ◽

2020 ◽

Vol 27 (5) ◽

pp. 837-849

Author(s):

Luis Alberto Solis-Castillo ◽

Gina Stella Garcia-Romo ◽

Alvaro Diaz-Rodriguez ◽

Diana Reyes-Hernandez ◽

Elizabeth Tellez-Rivera ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

T Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Stem Cells ◽

Regulatory T Cells ◽

Early Breast Cancer ◽

Node Metastasis

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Downregulated Long Noncoding RNA DGCR5 Acts as a New Promising Biomarker for the Diagnosis and Prognosis of Ovarian Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033819896809 ◽

2019 ◽

Vol 18 ◽

pp. 153303381989680

Author(s):

Hongxiao Chen ◽

Xiufang Tian ◽

Yajing Luan ◽

Hui Lu

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Distant Metastasis ◽

Critical Region ◽

Noncoding Rna ◽

Digeorge Syndrome ◽

Region Gene ◽

Node Metastasis

Emerging evidence have indicated that dysregulated long noncoding ribonucleic acids act as a novel diagnostic and therapeutic target in the progression of ovarian cancer. Long noncoding RNA DiGeorge syndrome critical region gene 5 has been reported to participate in some types of human cancer progresses, but its clinical roles in ovarian cancer had been rarely reported. This study aimed to explore the expression, clinicopathological features, diagnostic, and prognostic values of DiGeorge syndrome critical region gene 5 in ovarian cancer. The total levels of DiGeorge syndrome critical region gene 5 transcript variant 1 (NR_002733.2) and 2 (NR_045121.1) in patients with ovarian cancer were determined by quantitative reverse transcription polymerase chain reaction. The correlation of DiGeorge syndrome critical region gene 5 expression with clinicopathological factors was statistically analyzed by χ2 test. Overall survival analysis was carried out with the Kaplan–Meier curves with the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify the prognostic significance of DiGeorge syndrome critical region gene 5 expression. Receiver operating characteristic curves were constructed to estimate the diagnostic and prognostic usefulness of DiGeorge syndrome critical region gene 5 in ovarian cancer. Results showed that relative DiGeorge syndrome critical region gene 5 expression was reduced by 36.81% and 65.79% in ovarian cancer tissues of patients and Gene Expression Omnibus DataSets (GSE119056) in contrast to normal tissues, respectively. Patients with lymph node metastasis and distant metastasis exhibited lower levels of DiGeorge syndrome critical region gene 5 in contrast to those patients with non-lymph node metastasis and non-distant metastasis, respectively. Low expression of DiGeorge syndrome critical region gene 5 was significantly associated with large tumor size, more lymph node metastasis, present distant metastasis, advanced clinical stage, and short overall survival in patients with ovarian cancer. Low expression of DiGeorge syndrome critical region gene 5 was an independent unfavorable prognostic factor for overall survival in patients with ovarian cancer. Receiver operating characteristics curves for prognosis yielded significant area under curves for lymph node metastasis, clinical stage, and overall survival. In conclusion, our study demonstrated that downregulated DiGeorge syndrome critical region gene 5 may be a new promising biomarker for predicting clinical progression and prognosis in patients with ovarian cancer.

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