Distinct promotor methylation at tumor suppressive genes in ovarian cancer stromal progenitor cells and ovarian cancer and its clinical implication.

Aberrant CpG-island methylation affects ovarian cancer progression. The promotor methylation changes at tumor suppressive genes in ovarian cancer stromal progenitor cells (OCSPCs) and epithelial ovarian cancer (EOC) tissues and their clinical implication remains unexplored. We systemically analyzed the promoter methylation status of 40 tumor suppressor genes (TSGs) associated with cancer in paired epithelial-like and mesenchymal-like OCSPCs and ovarian cancer cells by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The effect of DNA methylation on gene expression was confirmed using qRT-PCR. The differential frequencies of TSGs' promoter methylation among matched epithelial-like or mesenchymal-like OCSPCs from tissues and ascites and ovarian cancer tissues were further validated in cancer tissues and correlated with clinicopathological features and survival outcomes of patients. According to the promoter methylation frequencies of the 40 TSGs, promoters of RASSF1A were the only significantly hypomethylated in epithelial-like OCSPCs from tissues than those from ascites and bulk tumor cells (0% vs 38% vs 45%, P=0.039 by Fisher's exact test). The most frequencies at promotor hypermethylation of TSGs in mesenchymal-like OCSPCs from ascites which processed aggressiveness were CDKN2B (73%) followed by CCND2 (45%) and RASSF1A (45%). Forty-three percent (47/110) of RASSF1A and 45% of CCND2 were validated as a frequently hypermethylated gene in an independent set of 110 EOC tissues in contrast to none (0/60) and 12% (10/60) of benign ovarian cysts (both P<0.001). Functional experiments revealed overexpression of CCND2 or CDKN2B in MSc-OCSPCs decreases EMT, invasion, and spheroid formation in EOC, and abolishes DNMT1 and COL6A3 expression. However, for the expected 5-year overall survival (OS) for patients with methylated RASSF1A, CCND2, and CDKN2B, only RASSF1A was significantly worse than those without methylated RASSF1A (56% vs 80%, p=0.022). Taken together, overexpression of CCND2 and CDKN2B decreased the aggressiveness of mesenchymal-like OCSPCs from ascites which may represent a potential therapeutic target for EOC. Promotor hypomethylation at RASSF1A in OCSPCs from EOC tissues and changes to hypermethylation of EOC and OCSPCs from ascites could predict poor survival outcomes for EOC patients compared to without those changes of CCND2 and CDKN2B.

Syndiotactic Poly(4-methyl-1-pentene)-Based Stereoregular Diblock Copolymers: Synthesis and Self-Assembly Studies.

Syndiotactic poly(4-methyl-1-pentene) (sP4M1P)-based stereoregular diblock copolymers, namely sP4M1P-b-polystyrene and sP4M1P-b-polymethylmethacrylate, were prepared from an α-bromoester-capped sP4M1P macroinitiator, which was chain extended with styrene and methyl methacrylate, respectively, via the atom transfer radical polymerization reaction. The α-bromoester-capped sP4M1P was generated by the esterification of hydroxyl-capped sP4M1P with α-bromoisobutyryl bromide. The hydroxyl-capped sP4M1P was synthesized by inducing a selective chain transfer reaction to aluminum during the syndiospecific polymerization of 4-methyl-1-pentene in the presence of a syndiospecific metallocene catalyst. As stereoregular diblock copolymers are difficult to prepare using existing methods, the current study offers an effective process for the preparation of sP4M1P-based stereoregular diblock copolymers. These copolymers were found to have well-defined architectures and they can undergo molecular self-assembly into ordered nanostructures, as evidenced by small-angle X-ray scattering analyses.

A solitary fibrous tumor of the ovary.

OBJECTIVE: We report a case of an ovarian solitary fibrous tumor (SFT), which rarely occurs in the female genital system. CASE REPORT: A 63-year-old postmenopausal woman resorted to the tertiary center seeking management for an intra-abdominal mass. Physical examination disclosed a local abdominal distention. Ultrasound revealed an 18-cm complex mass with inner neovascularization. A whole abdominal computed scan (CT) demonstrated an 18-cm abdominal tumor. The woman then underwent a left salpingo-oophorectomy. Histological examination and immunohistochemical stains of the tumor confirmed the diagnosis of SFT. The patient recovered uneventfully and remained free of recurrence 6 months postoperatively. CONCLUSION: SFTs in the female genital system are extremely rare and not fully understood. The metastatic risk of the patient was intermediate, according to the modified four-variable risk models based on the World Health Organization (WHO) classification of soft tissue tumors. Close monitoring with clinical evaluation and imaging studies will be conducted.

Cultivar-specific markers, mutations, and chimerisim of Cavendish banana somaclonal variants resistant to Fusarium oxysporum f. sp. cubense tropical race 4.

BACKGROUND: The selection of tissue culture-derived somaclonal variants of Giant Cavendish banana (Musa spp., Cavendish sub-group AAA) by the Taiwan Banana Research Institute (TBRI) has resulted in several cultivars resistant to Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), a destructive fungus threatening global banana production. However, the mutations in these somaclonal variants have not yet been determined. We performed an RNA-sequencing (RNA-seq) analysis of three TBRI Foc TR4-resistant cultivars: 'Tai-Chiao No. 5' (TC5), 'Tai-Chiao No. 7' (TC7), and 'Formosana' (FM), as well as their susceptible progenitor 'Pei-Chiao' (PC), to investigate the sequence variations among them and develop cultivar-specific markers. RESULTS: A group of single-nucleotide variants (SNVs) specific to one cultivar were identified from the analysis of RNA-seq data and validated using Sanger sequencing from genomic DNA. Several SNVs were further converted into cleaved amplified polymorphic sequence (CAPS) markers or derived CAPS markers that could identify the three Foc TR4-resistant cultivars among 6 local and 5 international Cavendish cultivars. Compared with PC, the three resistant cultivars showed a loss or alteration of heterozygosity in some chromosomal regions, which appears to be a consequence of single-copy chromosomal deletions. Notably, TC7 and FM shared a common deletion region on chromosome 5; however, different TC7 tissues displayed varying degrees of allele ratios in this region, suggesting the presence of chimerism in TC7. CONCLUSIONS: This work demonstrates that reliable SNV markers of tissue culture-derived and propagated banana cultivars with a triploid genome can be developed through RNA-seq data analysis. Moreover, the analysis of sequence heterozygosity can uncover chromosomal deletions and chimerism in banana somaclonal variants. The markers obtained from this study will assist with the identification of TBRI Cavendish somaclonal variants for the quality control of tissue culture propagation, and the protection of breeders' rights.

Everolimus combined with 5-aza-2-deoxycytidine generated potent anti-tumor effects on ovarian clear cell cancer stem-like/spheroid cells by inhibiting the COL6A3-AKT-mTOR pathway.

Ovarian clear cell cancer stem-like/spheroid cells (OCCCSCs) were associated with recurrence, metastasis, and chemoresistance in ovarian clear cell carcinoma (OCCC). We evaluated the anti-tumor effects of 5-aza-2-deoxycytidine (5-aza-dC) combined with everolimus (RAD001) on human OCCC. We investigated parental OCCCSCs and paclitaxel-resistant cell lines derived from OCCCSCs in vitro and in vivo. A Western blot analysis showed that the 5-aza-dC and RAD001 combination therapy was associated with the COL6A3-AKT-mTOR pathway. The OCCCSCs expressed high levels of stemness markers: CD117, ALDH1, NANOG, OCT4, and CD133. The 5-aza-dC and RAD001 combination inhibited proliferation and survival with up to 100-fold more potency in OCCCSCs compared to OCCC cells. This combination showed significant anti-tumor activity; it preferentially diminished OCCCSC stemness levels and spheroid numbers in vitro. Limiting dilution assays showed that OCCCSCs possessed tumor-initiating capacity. The 5-aza-dC and RAD001 combination significantly enhanced the inhibition of tumor growth compared to the 5-aza-dC or RAD001 alone. OCCCSCs showed higher expression levels of COL6A3, phospho-AKT, phospho-mTOR, and phospho-Rictor compared to OCCCs. Silencing COL6A3 or abolishing the phospho-AKT-mTOR-Rictor pathway with 5-aza-dC and RAD001 treatment further enhanced OCCCSC apoptosis and reduced OCCCSC stemness. In conclusion, 5-aza-dC combined with RAD001 effectively controlled OCCC and OCCCSC growth by inhibiting the COL6A3-AKT-mTOR pathway.

Correction: Weng et al. New International Association for the Study of Lung Cancer (IASLC) Pathology Committee Grading System for the Prognostic Outcome of Advanced Lung Adenocarcinoma. Cancers 2020, 12, 3426.

The authors would like to make a correction to their published paper [...].

Collagen type VI regulates the CDK4/6-p-Rb signaling pathway and promotes ovarian cancer invasiveness, stemness, and metastasis.

The expression of collagen VI in primary ovarian tumors may correlate with tumor grade and response to chemotherapy. We have sought to elucidate the role of collagen VI in promoting ovarian cancer tumor growth and metastasis. Here we examined the effects of collagen VI on ovarian carcinoma stromal progenitor cells (OCSPCs). Epithelial-like OCSPCs (epi-OCSPCs) and mesenchymal-like OCSPCs (msc-OCSPCs) were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Differentially expressed genes were integrated with survival-related genes using The Cancer Genome Atlas (TCGA) data and confirmed in our samples. The roles of candidate genes and signaling pathways were further explored. We found that SKOV3/msc-OCSPCs possessed greater migration, invasion, and spheroid formation than SKOV3/epi-OCSPCs (P < 0.001). Expression of collagen alpha-3 (VI; COL6A3), which encodes collagen VI, was 90-fold higher in msc-OCSPCs than in epi-OCSPCs. Analysis of TCGA data and our samples indicated that high expression of COL6A3 was correlated with advanced-stage carcinoma (P < 0.01) and shorter overall survival (P < 0.01). In vitro, adding collagen VI, msc-OCSPCs, or knockdown collagen VI in msc-OCSPCs to epithelial ovarian carcinoma (EOC) cells augmented or decreased invasion and spheroid formation. Tumor dissemination to the peritoneal cavity and lung in mice following intraperitoneal coinjection with msc-OCSPCs and SKOV3-Luc cells and intravenous injection with COL6A3 and ES2 cells derived spheroids was significantly greater compare to coinjection with SKOV3-Luc cells alone or in combination with msc-OCSPCs/shCOL6A3 cells and msc-OCSPCs and ES2 derived spheroids. Knockdown of COL6A3 abolished the expression of DNMT1, CDK4, CDK6, and p-Rb in msc-OCSPCs and EOC spheroids. In contrast, overexpression of COL6A3 enhanced the expression of CDK4, CDK6, and p-Rb in SKOV3 cells. EOC spheroid formation, invasion, tumor growth, and metastasis were inhibited when COL6A3 downstream signaling pathway was blocked using CDK4/6 inhibitor LEE011. Our results suggested that collagen VI regulates the CDK4/6-p-Rb signaling pathway and promotes EOC invasiveness, stemness, and metastasis.

New International Association for the Study of Lung Cancer (IASLC) Pathology Committee Grading System for the Prognostic Outcome of Advanced Lung Adenocarcinoma.

The impact of the new International Association for the Study of Lung Cancer pathology committee grading system for advanced lung adenocarcinoma (LADC) on survival is unclear, especially in Asian populations. In this study, we reviewed the prognostic outcomes of patients with late-stage disease according to the new grading system. We reviewed 136 LADC cases who underwent a small biopsy from 2007 to 2018. Tumors were classified according to the new grading system for LADC. Baseline characteristics (age, sex, smoking status, body mass index, and driver gene mutations) were analyzed. Kaplan-Meier and Cox regression analyses were used to determine correlations with the new grading system and prognosis. Patients with poorly differentiated adenocarcinoma were significantly correlated with a poor progression-free survival (PFS) (p = 0.013) but not overall survival (OS) (p = 0.154). Subgroup analysis showed that wild-type EGFR patients with poorly differentiated adenocarcinoma treated with chemotherapy had significantly worse PFS (p = 0.011). There was no significant difference in survival among the patients with epidermal growth factor receptor mutations who were treated with tyrosine kinase inhibitors. Patients aged >70 years and those with a BMI ≤ 25 kg/m2 and wild-type patients had significantly worse OS in both univariate (HR = 1.822, p = 0.006; HR = 2.250, p = 0.004; HR = 1.537, p = 0.046, respectively) and multivariate analyses (HR = 1.984, p = 0.002; HR = 2.383, p = 0.002; HR = 1.632, p = 0.028, respectively). Despite therapy, patients with poorly differentiated tumors still fared worse than those with better differentiated tumors. No differences were found among the EGFR mutations treated with TKI. Our findings highlight that the therapeutic regimen should be adjusted for EGFR Wild-type patients with poorly differentiated adenocarcinoma treated with chemotherapy to provide better outcomes.

Yolk sac tumor of endometrium: A case report and literature review.

OBJECTIVE: To report a rare case of endometrial yolk sac tumor (YST) and review published cases of YST of the endometrium. CASE REPORT: A 68-year-old female presented with intermittent vaginal spotting for nine months. An endometrial biopsy showed adenocarcinoma. Complete surgical staging operation was performed and the final pathology revealed stage II endometrial yolk sac tumor. The post-operative α-fetoprotein (AFP) level was 133.4 ng/mL. Post-operative adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP) regimen was prescribed for 6 cycles. AFP levels were normal before the fourth cycle of chemotherapy. She is disease free 6 months after completion of therapy. CONCLUSION: Primary YSTs arising in the endometrium is an extremely rare disease especially in postmenopausal women. Complete surgical staging operation with adjuvant chemotherapy will lead to good outcome in this disease.

Unusual synchronous double primary treatment-naïve lung adenocarcinoma harboring T790M and L858R mutations in early-stage lung cancer.

BACKGROUND: Concurrent mutations of synchronous multiple primary non-small cell lung cancer (SMPNSCLC) is rare, and only a few cases have been reported. Herein, we present a case of early-stage SMPNSCLC with T790M and L858R mutations. CASE PRESENTATION: A 68-year-old male patient presented to the Thoracic Surgery Department due to a tumor in the right lower lung. The tumor was detected more than 5 years previously during a health examination; however, the patient ignored the problem because the clinician at that time stated that the lesion was highly likely to be benign. Chest computed topography (CT) was ordered and the images showed a well-defined tumor in the right lower lung and a faint nodular lesion over the left lower lung field. A CT-guided biopsy results showed the presence of atypical cells and positive staining of TTF-1 and CK7. Surgical intervention was performed. The right- and left-sided tumors disclosed micropapillary predominant adenocarcinoma and acinar-predominant adenocarcinoma, respectively. Both tumors were positive for TTF-1 but negative for ALK and p40. Real-time PCR analysis showed that the right-sided tumor had an epidermal growth factor receptor (EGFR) mutation presenting as point mutation T790M in exon 20, while the left-sided tumor had a point mutation L858R in exon 21 of EGFR. CONCLUSIONS: Our patient's case suggests that tumors resembling a benign pattern with central calcification may be misdiagnosed. Thus, early screening for lung cancer is important, and intensive efforts to make a diagnosis through surgical resection or biopsies to allow for tailored optimal treatment may be preferential for the best patient outcomes.

Polypoid endometriosis - A rare entity of endometriosis mimicking ovarian cancer.

OBJECTIVE: To report a rare case of polypoid endometriosis with initial impression of ovarian cancer and review the published literature about this disease. CASE REPORT: A 23-year-old female presented with sudden onset of acute lower abdominal pain. Image studies revealed an irregular shaped, heterogeneous mass at the cul-de-sac, but without ascites or enlargement of pelvic or paraaortic lymph nodes. Blood tests showed an elevated CA-125 value (1317 U/ml). Resection of the mass was performed by laparotomy and the frozen section and final pathology both revealed polypoid endometriosis. Post-operative gonadotropin-releasing hormone agonist was given for 6 months followed by oral contraceptives. She remained disease free 3 years after operation. CONCLUSION: Polypoid endometriosis is an uncommon and distinctive variant of endometriosis. Gynecologists should be aware of this rare form of a commonly benign disease to avoid excessive resection in younger patients of childbearing age.

Pilot Study to Establish a Novel Five-Gene Biomarker Panel for Predicting Lymph Node Metastasis in Patients With Early Stage Endometrial Cancer.

Introduction: In the United States and Europe, endometrial endometrioid carcinoma (EEC) is the most prevalent gynecologic malignancy. Lymph node metastasis (LNM) is the key determinant of the prognosis and treatment of EEC. A biomarker that predicts LNM in patients with EEC would be beneficial, enabling individualized treatment. Current preoperative assessment of LNM in EEC is not sufficiently accurate to predict LNM and prevent overtreatment. This pilot study established a biomarker signature for the prediction of LNM in early stage EEC. Methods: We performed RNA sequencing in 24 clinically early stage (T1) EEC tumors (lymph nodes positive and negative in 6 and 18, respectively) from Cathay General Hospital and analyzed the RNA sequencing data of 289 patients with EEC from The Cancer Genome Atlas (lymph node positive and negative in 33 and 256, respectively). We analyzed clinical data including tumor grade, depth of tumor invasion, and age to construct a sequencing-based prediction model using machine learning. For validation, we used another independent cohort of early stage EEC samples (n = 72) and performed quantitative real-time polymerase chain reaction (qRT-PCR). Finally, a PCR-based prediction model and risk score formula were established. Results: Eight genes (ASRGL1, ESR1, EYA2, MSX1, RHEX, SCGB2A1, SOX17, and STX18) plus one clinical parameter (depth of myometrial invasion) were identified for use in a sequencing-based prediction model. After qRT-PCR validation, five genes (ASRGL1, RHEX, SCGB2A1, SOX17, and STX18) were identified as predictive biomarkers. Receiver operating characteristic curve analysis revealed that these five genes can predict LNM. Combined use of these five genes resulted in higher diagnostic accuracy than use of any single gene, with an area under the curve of 0.898, sensitivity of 88.9%, and specificity of 84.1%. The accuracy, negative, and positive predictive values were 84.7, 98.1, and 44.4%, respectively. Conclusion: We developed a five-gene biomarker panel associated with LNM in early stage EEC. These five genes may represent novel targets for further mechanistic study. Our results, after corroboration by a prospective study, may have useful clinical implications and prevent unnecessary elective lymph node dissection while not adversely affecting the outcome of treatment for early stage EEC.

Tacticity effects in side-chain photoluminescent polymers.

Stereoregular side-chain photoluminescent (PL) polymers were synthesized via the stereospecific polymerization of 9,9-dibutyl-2-(4-vinylphenyl)-9H-fluorene. The resulting isotactic, syndiotactic and atactic poly(9,9-dibutyl-2-(4-vinylphenyl)-9H-fluorene) polymers were used as stereoregular polymer samples for examining the configurational tacticity effect on their PL properties. Our results revealed a unique tacticity-dependent effect as observed by an obvious red-shifting of the PL emission by increasing the degree of isotacticity of these stereoregular polymers; despite the ultraviolet spectra of these polymers exhibited similar absorption patterns. This study provides a new structural design for the syntheses of PL polymers.

EBV-associated lymphoepithelioma-like thyroid carcinoma with favorable outcome: case report with cytopathologic and histopathologic study.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare entity among thyroid tumors. Based on the limited number of case reports that exist, the association of Epstein-Barr virus (EBV) with primary thyroid LELCs seems inconsistent. CASE PRESENTATION: We present a confusing cytological case of lymphoepithelioma-like thyroid carcinoma with expression of EBV. The patient presented with a central neck mass and bilateral lymphadenopathy. Fine-needle aspiration cytology revealed three-dimensional and syncytial fragments of epithelioid cells accompanied by small lymphocytes. The surgical specimen of resected thyroid tumor disclosed typical histopathological features of LELC. Metastatic papillary carcinoma was also discovered in the metastatic lymph nodes. In situ hybridization for EBV-encoded RNA (EBER-ISH) was positive in the tumor cells. Negative immunoreactivity for TTF-1, Pax-8, and CD5 was observed. The patient is currently undergoing regular follow-up and is 1 year and 10 months postresection with no evidence of recurrence. CONCLUSIONS: Long-term survival is discussed in relation to this variant of thyroid carcinoma, which might differ in behavior from anaplastic carcinoma. Further investigation is required to elucidate the clinical significance of EBV expression and progression of this unique variant of thyroid carcinoma.

Everolimus following 5-aza-2-deoxycytidine is a promising therapy in paclitaxel-resistant clear cell carcinoma of the ovary.

Our previous study showed that 5-aza-2-deoxycytidine (5-aza-dC) could inhibit tumor growth by enhancing the susceptibility of ovarian clear cell carcinoma (OCCC) to paclitaxel through decreasing AKT/mTOR expressions. The objective of the study is to evaluate the antitumor efficacy of everolimus (RAD001) and 5-aza-2-deoxycytidine (5-aza-dC) by targeting AKT/mTOR and EZH2 in OCCC. Paclitaxel-sensitive and resistant OCCC cell lines were established. In vitro proliferative and apoptotic assays and flow cytometry were performed. The expressions of EZH2, PIK3IP1, phospho-AKT, phospho-mTOR and phospho-Rictor in the OCCC cell lines were evaluated by Western blotting. In vivo animal experiments with RAD001 and 5-aza-dC were performed. RAD001 alone showed significant in vitro antitumor activity and inhibited in vivo tumor growth in paclitaxel-sensitive and resistant OCCC cells. In addition, 5-aza-dC enhanced the antitumor effects when combined with paclitaxel or RAD001 in both paclitaxel-sensitive and resistant tumors. Activation of phospho-AKT ser473 and PIK3IP1 was observed in RAD001-treated paclitaxel-sensitive and resistant OCCC cells. In contrast, inhibition of phospho-AKT ser473 and EZH2 was observed with RAD001 following 5-aza-dC treatment of paclitaxel-sensitive and resistant OCCC cells. Furthermore, RAD001 following 5-aza-dC enhanced apoptosis of paclitaxel-sensitive and resistant OCCC cells. RAD001 following 5-aza-dC may be a promising treatment strategy for the treatment of both chemo-sensitive and resistant OCCC. Further clinical studies are warranted.

Low-grade fibromyxoid sarcoma of the external anal sphincter: a case report.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor that has a tendency to grow in the deep soft tissue of the trunk and extremities. Despite its benign appearance, the tumor has a high recurrence rate and metastatic potential. LGFMS in the perineal space is rare, and only a few cases have been reported. We present the first case of LGFMS to be located at the external anal sphincter. CASE PRESENTATION: A 27-year-old male patient admitted to our Surgical Department with perianal pain and swollen for a year. The digital rectal examination revealed a perianal mass. Oral metronidazole and analgesia were prescribed on suspicion of perianal abscess failed to alleviate the symptom; hence, the patient was scheduled for surgery. Intraoperative diagnosis revealed an encapsulated tumor in the external anal sphincter that extended from the perianal region orally to the pararectal space. The results of immunohistochemistry (MUC4 staining) and FUS gene rearrangement by fluorescence in situ hybridization confirmed the diagnosis of LGFMS. CONCLUSIONS: This case is unique in terms of the location of the rare soft tissue tumor. Although LGFMS is considered low grade, its unpredictable behavior necessitates a long-term follow-up.

Detection of lower levels of SNAP25 using multiple microarray systems and its functional significance in medulloblastoma.

Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with high-risk or recurrent MB respond poorly to current therapies, and have a higher related mortality. For this reason, potential molecules related to MB need be identified in order to develop targets for the development of novel therapeutics. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function 'vesicle' were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), was found to have significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells as shown by western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 altered the morphology and the chemotherapeutic effects of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. On the whole, our data indicate that the expression of SNAP25 is crucial for dendrite formation and is associated with the effects of targeted chemotherapy. The detection of SNAP25 expression in MB cells may thus be essential for the chemotherapeutic application of Ara-C.