Testicular germ cell tumors (TGCTs) frequently affect adolescent and young adult males. Although TGCT is more responsive to cisplatin-based chemotherapy than other solid tumors, some patients are nonresponders, and following treatment, many patients continue to experience acute and long-term cytotoxic effects from cisplatin-based chemotherapy. Consequently, it is imperative to develop new therapeutic modalities for treatment-resistant TGCTs. Peptidyl-prolyl isomerase (Pin1) regulates the activity and stability of many cancer-associated target proteins. Prior findings suggest that Pin1 contributes to the pathogenesis of multiple human cancers. However, the specific function of Pin1 in TGCTs has not yet been elucidated. TGCT cell proliferation and viability were examined using cell cycle analysis and apoptosis assays following treatment with KPT6566, a potent, selective Pin1 inhibitor that covalently binds to the catalytic domain of Pin1. A xenograft mouse model was used to assess the effect of KPT6566 on tumor growth in vivo. KPT6566 effectively suppressed cell proliferation, colony formation, and ATP production in P19 and NCCIT cells. Further, KPT6566 induced apoptotic cell death by generating cellular reactive oxygen species and downregulating the embryonic transcription factors Oct-4 and Sox2. Finally, KPT6566 treatment significantly reduced tumor volume and mass in P19 cell xenografts. The Pin1 inhibitor KPT6566 has significant antiproliferative and antitumor effects in TGCT cells. These findings suggest that Pin1 inhibitors could be considered as a potential therapeutic approach for TGCTs.

UNASSIGNED: Despite the follow-up protocols developed in non-muscle-invasive bladder cancer patients, progression and recurrence could not be prevented.
UNASSIGNED: We aimed to investigate whether proteins such as OCT-4, CD47, p53, Ki-67, and Survivin, which increase in bladder cancer cells, can be used as prognostic markers for patients with non-muscle-invasive bladder cancer.
UNASSIGNED: The study included a total of 89 patients with newly diagnosed non-muscle-invasive bladder cancer between January 2015 and December 2020.
UNASSIGNED: Levels of OCT-4, CD47, p53, Kİ-67, and Survivin proteins in cancer cells were determined with a semi-quantitative immunohistochemical experiment. Pathological data and survival rates were compared according to the staining rates.
UNASSIGNED: Data obtained in the study were analyzed statistically with SPSS 22.0 (SPSS, Chicago, IL, USA).
UNASSIGNED: The mean age of the patients was 64.25 ± 9.91 years, and the median follow-up period was 55 months. Recurrence rate was determined to be 36% (n = 32), and the rate of progression at 40.4% (n = 36). The staining rates were stronger for each marker in the progression group and advanced-stage tumors (p < 0.001). The findings of the multivariate analysis carried out as part of the study showed that older age and higher tumor stage were independent risk factors for recurrence-free survival (HR = 1.048 and 7.074, respectively; P = 0.02). Also, higher tumor stages, diameters, and grades were associated with reduced progression-free survival (HR = 0.105, 0.395, 0.225, respectively; P < 0.05).
UNASSIGNED: Although immunohistochemical staining rates are promising, it is more appropriate to use tumor characteristics when assessing survival rate in patients with non-muscle-invasive bladder cancer.

The endometrium is the inner mucosal lining of the uterus that undergoes extensive cyclic growth, regeneration, differentiation, and shedding throughout the menstrual cycle in response to steroid hormones. It repeatedly undergoes approximately 450 cycles of degeneration and regeneration in a woman\'s lifetime. Endometrial abnormalities can be associated with repeated embryo implantation failure, recurrent spontaneous abortion, and other physiological features responsible for female infertility. This significant regenerative capacity may occur as a result of tissue-resident stem cell populations within the endometrium. Indeed, the existence of endometrial stem cells was only observed in humans and rodents through several isolation and characterization methods in the last few years. Although endometrial stem cells share various biological characteristics with other types of mesenchymal stem cells, they also show some differences in phenotype, self-renewal, and multilineage differentiation potential. Extensive studies over many years on endometrial stem cells will provide new insights into the physiology and mechanisms underlying various gynaecological diseases related to endometrial abnormalities such as female infertility, endometriosis, and endometrial cancer. Here we summarized recent studies about cellular origins and biological characteristics of endometrial stem cells. We also reviewed various recent studies to improve our understanding of their physiological roles. Many preclinical studies on their potential therapeutic applications to various endometrial diseases that could lead to reproductive dysfunction were also reviewed.

Subependymal giant cell astrocytoma (SEGA) is a rare, slow-growing tumor with a dual (neuroglial) component that is typically associated with tuberous sclerosis complex (TSC). We present the case of a healthy 19-year-old man with mild occipital trauma followed by two weeks of intense headache, with no response to analgesics. Imaging studies revealed a well-defined tumor in the left paraventricular zone. A biopsy showed a SEGA (GFAP+, NF+, nestin+, CK-EA3/EA4+, and TTF1+). TSC was ruled out. An immunohistochemistry (IHC) panel showed aberrant cytoplasmic expression of octamer-binding transcription factor 4 (OCT-4) in endothelial cells, pericytes, and some astrocyte-type cells; integrase interactor 1 (INI-1) expression was observed in the cytoplasm of neoplastic cells; SEGA was not associated with TSC; the expression of nestin and OCT-4 suggested their origin in neuroepithelial stem cells; thyroid transcription factor 1 (TTF-1) expression supported its origin in diencephalic structures. Tuberin expression was decreased. An aberrant pattern of INI-1 was observed, which, together with OCT-4 findings, has not been previously described.

Very small embryonic like stem cells (VSELs) are a dormant population of stem cells that, as proposed, are deposited during embryogenesis in various tissues, including bone marrow (BM). These cells are released under steady state conditions from their tissue locations and circulate at a low level in peripheral blood (PB). Their number increases in response to stressors as well as tissue/organ damage. This increase is evident during neonatal delivery, as delivery stress prompts enrichment of umbilical cord blood (UCB) with VSELs. These cells could be purified from BM, PB, and UCB by multiparameter sorting as a population of very small CXCR4+ Lin- CD45- cells that express the CD34 or CD133 antigen. In this report, we evaluated a number of CD34+ Lin- CD45- and CD133+ Lin- CD45- UCB-derived VSELs. We also performed initial molecular characterization of both cell populations for expression of selected pluripotency markers and compared these cells at the proteomic level. We noticed that CD133+ Lin- CD45- population is more rare and express, at a higher level, mRNA for pluripotency markers Oct-4 and Nanog as well as the stromal-derived factor-1 (SDF-1) CXCR4 receptor that regulates trafficking of these cells, however both cells population did not significantly differ in the expression of proteins assigned to main biological processes.

The presence of stem cells has been previously described in human precancerous and malignant cervical cultures. Previous studies have shown a direct interplay of the stem cell niche, which is present in practically every tissue with the extracellular matrix. In the present study, we sought to determine the expression of stemness markers in cytological specimens collected from the ectocervix among women with cervical insufficiency during the second trimester of pregnancy and women with normal cervical length. A prospective cohort of 59 women was enrolled of whom 41 were diagnosed with cervical insufficiency. The expression of OCT-4 and NANOG was higher in the cervical insufficiency group compared to the control group (-5.03 (-6.27, -3.72) vs. -5.81 (-7.67, -5.02) p = 0.040 for OCT4) and (-7.47 (-8.78, -6.27) vs. -8.5 (-10.75, -7.14), p = 0.035 for NANOG. Differences in the DAZL gene were not significantly different (5.94 (4.82, 7.14) vs. 6.98 (5.87, 7.43) p = 0.097). Pearson correlation analysis indicated the existence of a moderate correlation of OCT-4 and Nanog with cervical length. Considering this information, the enhanced activity of stemness biomarkers among pregnant women diagnosed with cervical insufficiency may be predisposed to cervical insufficiency, and its predictive accuracy remains to be noted in larger population sizes.

Cancer continues to remain a \"Black Box,\" as there is no consensus on how it initiates, progresses, metastasizes, or recurs. Many imponderables exist about whether somatic mutations initiate cancer, do cancer stem cells (CSCs) exist, and if yes, are they a result of de-differentiation or originate from tissue-resident stem cells; why do cancer cells express embryonic markers, and what leads to metastasis and recurrence. Currently, the detection of multiple solid cancers through liquid biopsy is based on circulating tumor cells (CTCs) or clusters, or circulating tumor DNA (ctDNA). However, quantity of starting material is usually adequate only when the tumor has grown beyond a certain size. We posit that pluripotent, endogenous, tissue-resident, very small embryonic-like stem cells (VSELs) that exist in small numbers in all adult tissues, exit from their quiescent state due to epigenetic changes in response to various insults and transform into CSCs to initiate cancer. VSELs and CSCs share properties like quiescence, pluripotency, self-renewal, immortality, plasticity, enrichment in side-population, mobilization, and resistance to oncotherapy. HrC test, developed by Epigeneres, offers the potential for early detection of cancer using a common set of VSEL/CSC specific bio-markers in peripheral blood. In addition, NGS studies on VSELs/CSCs/tissue-specific progenitors using the All Organ Biopsy (AOB) test provide exomic and transcriptomic information regarding impacted organ(s), cancer type/subtype, germline/somatic mutations, altered gene expressions, and dysregulated pathways. To conclude, HrC and AOB tests can confirm the absence of cancer and categorize the rest of subjects into low/moderate/high risk of cancer, and also monitor response to therapy, remission, and recurrence.

OBJECTIVE: Research has suggested that tumor-initiating tumor stem cells are derived from normal stem cells and that tumor cells undergo progressive de-differentiation to achieve a stem cell-like state. Tumor stem cells are characterized by high proliferation ability, high plasticity, expression of multi-drug resistance proteins, and the ability to seed new tumors. Octamer-binding transcription factor 4 (Oct-4) and its activation targets are overexpressed in the tumor stem cells of various types of tumors, and this expression is associated with the pathogenesis, development, and poor prognosis of tumors. The primary objective of this study was to test if a stably transfected with Oct-4 gene cell line, RL95-2/Oct-4, has the characteristics of tumor stem cells.
METHODS: Human endometrial carcinoma cells (RL95-2) were transfected with a plasmid carrying genes for Oct-4 and green fluorescent protein (GFP). The stably transfected cells, RL95-2/Oct-4, were selected using G418 and observed to express the GFP reporter gene under the control of the Oct-4 promoter. GFP expression levels of RL95-2/Oct-4 cells were measured using flow cytometry. The proliferation potential of cells was determined according to cumulative population doubling and colony-formation efficiency. Gene expression was analyzed using reverse transcription-polymerase chain reaction.
RESULTS: RL95-2/Oct-4 cells not only exhibited increased expression of the three most important stem cell genes, Oct-4, Nanog, and Sox2, but also had increased expression of the endometrial tumor stem cell genes CD133 and ALDH1. Furthermore, enhanced expression of these genes in the RL95-2/Oct-4 cells was associated with higher colony-forming ability and growth rate than in parental RL95-2 cells. We also observed that cisplatin induced less cell death in RL95-2/Oct-4 cells than in RL95-2 cells, indicating that RL95-2/Oct-4 cells were more resistant to chemotherapeutic agents.
CONCLUSIONS: The study findings contribute to investigate the effects of Oct-4 on tumor stem cell origins.

At present, the treatment of hepatocellular carcinoma (HCC) is disturbed by the treatment failure and recurrence caused by the residual liver cancer stem cells (CSCs). Therefore, drugs targeting HCC CSCs should be able to effectively eliminate HCC and prevent its recurrence. In this study, we demonstrated the effect of Polyphyllin VII (PP7) on HCC CSCs and explored their potential mechanism.
HepG2 and Huh7 cells were used to analyze the antitumor activity of PP7 by quantifying cell growth and metastasis as well as to study the effect on stemness.
Our results demonstrated that PP7 promoted apoptosis and significantly inhibited proliferation and migration of both HepG2 and Huh7 cells. PP7 also inhibited tumor spheroid formation and induced significant changes in the expression of stemness markers (CD133 and OCT-4). These effects of PP7 were mediated by STAT3 signaling.
PP7 can effectively suppress tumor initiation, growth, and metastasis and inhibit stemness through regulation of STAT3 signaling pathway in liver cancer cells. Our data would add more evidence to further clarify the therapeutic effect of PP7 against HCC.

Liver stemness refers to the high regenerative capacity of the organ. This intrinsic regeneration capacity allows the restoration of post-resection liver function in up to 50% of liver donors. Liver cirrhosis is one of the terminal liver diseases with a defect in the intrinsic regeneration capacity. Several attempts to restore intrinsic regeneration capacity by conducting in vivo studies on stem cells in various organs have shown the positive impact of fasting on stemness. An increased capacity for stem cell proliferation and regeneration was reported due to fasting. Prolonged fasting (PF) has been reported to maintain the long-term proliferative ability of hematopoietic stem cells. However, clinical trials on intermittent fasting (IF) have not conclusively given positive results for fasting individuals.
This research aims to investigate the effect of fasting on liver stemness by comparing the expression of octamer-binding transcription factor 4 (Oct-4), cytokeratin 19 (CK-19), and peroxisome proliferator-activated receptor γ co-activator α (PGC-1α) in liver cells of fasted rabbits with rabbits fed ad libitum. This study compares two types of fasting, which are intermittent (16 hours) and prolonged (40 hours) fasting, for liver stemness and intrinsic regenerative capacity.
A total of 18 rabbits were conditioned into 3 different groups. The first group was subjected to an ad libitum diet, the second to intermittent fasting (16-hour fasting), and the third to prolonged fasting (40-hour fasting). Afterward, the RNA was extracted from the liver tissues of each rabbit and analyzed via real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Relative expression was calculated using the Livak method.
Compared to the ad libitum diet, a greater increase was reported in PGC-1α, upregulated Oct4, and steady CK-19 gene expressions in the livers of intermittent fasting rabbits. Prolonged fasting increased PGC1α, reduced liver stemness, and a statistically insignificant decrease in intrinsic liver regenerative capacity.
Intermittent fasting indicates preferable molecular alterations in liver stemness and intrinsic regenerative capacity compared to prolonged fasting.