CCL26 is upregulated by nab-paclitaxel in pancreatic cancer-associated fibroblasts and promotes PDAC invasiveness through activation of the PI3K/AKT/mTOR pathway.

Recently, the combined use of FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel has significantly improved the prognosis of patients with pancreatic cancer. However, there is still a high proportion of patients who develop metastatic pancreatic cancer in the course of chemotherapy or within a short period after chemotherapy. Previous reports have shown that chemotherapy-driven cytokine storms or the direct effects of certain chemotherapeutics on stromal and/or immune cells collectively change the microenvironment of the primary tumor, thus indirectly promoting metastasis. However, the mechanism underlying chemotherapy-induced metastasis in the course of chemotherapy, and afterwards, remains elusive in pancreatic cancer. In the present study, we aimed to determine the expression of CCL26 in the pancreatic cancer-associated fibroblasts (CAFs) after nab-paclitaxel treatment and to explore the role of CCL26 in the pancreatic adenocarcinoma (PDAC) invasion. Our results showed that nab-paclitaxel increased CCL26 mRNA and protein expression levels in a dose- and time-dependent manner. Subsequently, PDAC cell lines were treated with recombinant CCL26 for 48 h. The transwell migration assay showed that recombinant CCL26 enhanced the invasion of PDAC cells. Western blot analysis showed that the protein expression levels of phospho-(p-)PI3K, p-AKT, and p-mTOR were increased by CCL26 in PDAC cells. CCL26 expressions in 95 PDAC tissues and adjacent normal tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. CCL26 was found to be overexpressed in PDAC samples, and upregulated CCL26 expression was significantly associated with advanced perineural invasion, lymph node metastasis, and poor differentiation. In summary, our results showed that nab-paclitaxel increased the expression of CCL26 in CAFs, and CCL26 enhanced the invasive potential of pancreatic cancer cells by activating the PI3K/AKT/mTOR axis. Thus, CCL26 may be a potential prognostic biomarker for pancreatic cancer.

Prediction of nuclear grade of clear cell renal cell carcinoma with MRI: intratumoral susceptibility signal intensity versus necrosis.

BACKGROUND: End-stage renal disease and dialysis patients have a higher incidence of renal cell carcinoma (RCC) than the general population. Preoperatively evaluating the biological behavior of RCC plays an important role in treatment decision-making. Susceptibility-weighted imaging (SWI) can visualize the distribution of microvenous structures and hemorrhage without contrast materials. PURPOSE: To evaluate the feasibility of SWI in grading clear cell RCCs (CRCC) and compare the ability of SWI and necrosis for grading CRCCs. MATERIAL AND METHODS: Retrospective reviews of 35 patients with pathologically-proven CRCCs were performed. All patients underwent both conventional magnetic resonance imaging (MRI) and SWI examinations. The morphology of the intratumoral susceptibility signal intensities (ITSS) was classified into hemorrhage and microvessels. The differences of ITSSs on SWI and necrosis between low- and high-grade CRCCs were assessed. The diagnostic values of ITSSs and necrosis in differentiating low- from high-grade CRCCs were compared by receiver-operating characteristics. RESULTS: ITSSs were seen in 31 of 35 patients. No ITSSs were seen in four patients with low-grade CRCCs. Mean scores of ITSSs on SWI were significantly lower for low-grade CRCCs (1.24 ± 0.72) than that for the high-grade CRCCs (2.70 ± 0.48). No significant necrosis was seen in 10 patients with low-grade CRCCs. There was a significant difference of the presence of intratumoral necrosis between low- and high-grade CRCCs. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were for ITSSs: 70%, 100%, 100%, and 89.3%, respectively; for necrosis: 100%, 40%, 40%, and 100%. CONCLUSION: SWI can evaluate ITSSs without contrast materials and can be an alternative to grading CRCCs preoperatively for some special patients.

Low-grade oncocytic tumour (LOT) of the kidney is characterised by GATA3 positivity, FOXI1 negativity and mTOR pathway mutations.

Aims: We present a 5-case series of low-grade oncocytic tumour of the kidney to further discuss their clinicopathological characteristics. Methods and results: Five patients were included in this study. There were three females and two males aged 45-66 years, with a median age of 65 years. Four tumours were located in the right kidney, and one was located in the left kidney. Most of the tumour sections were yellow-brown in colour. Tumour sizes ranged from 2.5 to 4.5 cm, with a median size of 3 cm. Microscopically, the tumours were well-circumscribed but lacked a fibrous capsule; the tumours consisted of monomorphous oncocytic cells arranged mainly in solid and nested architectural patterns. The tumour cells had uniformly round to oval nuclei and often had perinuclear halos but lacked significant irregularities. Immunohistochemically, the tumour cells showed a diffuse and strong positivity for CK7 and were negative for CD117. The tumour cells were also positive for GATA3, E-cadherin, Pax-8, Succinate dehydrogenase B (SDHB) and Fumarate hydratase (FH), and negative for vimentin, Carbonic anhydrase 9 (CA9), CD10, P504s, CK20, TFE3, TFEB, HMB45, ALK and Forkhead box protein I1 (FOXI1). Next-generation sequencing identified genetic variations in these tumours, including MTOR gene mutations (4/5) and PIK3CA gene mutation (1/5). All patients were alive without disease progression at a median follow-up of 32 months (range 10-57 months). Conclusion: LOT is an emerging renal entity of indolent behaviour that has morphologic overlap with some renal tumours with eosinophilic cytoplasm, primarily with oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma. Familiarity with the distinctive morphological features, immunophenotype and molecular genetics of LOT helps avoid misdiagnosis.

The genomic profile of double primary secretory breast carcinoma in one patient provides evidence for the treatment of such carcinoma: A case report.

Secretory breast carcinoma (SBC) is one of the rarest breast carcinomas and currently lacks a standard treatment regimen. To date, few reports on double primary SBCs have been published, especially regarding the tumors' genomic features. A 51-year-old woman with early SBC who developed a secondary SBC in the contralateral mammary tissue 140 months later was evaluated. Here, we describe for the first time the sequencing results of a Chinese patient with nonsimultaneous double-primary SBC. In addition to the ETV6-NTRK3 fusion, variants in polymorphisms of enzymes related to drug metabolism variant genes, including BCL2L11, CYP2B6, CYP2C19, ERCC1, GSTM1, GSTP1, MTHFR, NQO1, TYMS, and XRCC, were present according to 425-gene DNA sequencing. The ETV6-NTRK3 fusion site was different between the tumors; furthermore, whole-gene exon sequencing revealed that genetic variation spectrum of the two tumors was different. A POLDIP2 mutation was found in the first tumor, and HDLBP, MMP2, PLEKHA6 and ZNF285 variants were detected in the second tumor. Our findings further our understanding of the molecular pathogenesis of SBCs, especially regarding tumors occurring at different times in one patient. Further molecular analyses of such cases are warranted to improve targeted therapies for SBC.

Primary Sclerosing Epithelioid Fibrosarcoma of the Kidney: A Case Report and Review of the Literature.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of fibrosarcoma. We report one case of primary kidney SEF occurring in a 38-year-old man. Microscopically, epithelioid neoplastic cells are mainly arranged in cords and nests embedded in the dense sclerosing stroma. Diffuse immunohistochemical staining for MUC4 in neoplastic cells and the presence of the EWSR1 gene split by fluorescence in situ hybridization (FISH) analysis confirmed the histological diagnosis. Primary kidney SEF is extremely rare, the differential diagnosis strategy broadly includes a series of tumors with epithelioid morphology and sclerosing matrix, mainly including sclerosing variants of clear cell sarcoma of the kidney (CCSK), renal synovial sarcoma (SS), renal solitary fibrous tumor (SFT), metanephric stromal tumor (MST), sclerosing perivascular epithelioid cell tumor (PEComa), and carcinomas, and immunohistochemical expression of MUC4 and evidence of the EWSR1 gene split are helpful in making a definite diagnosis.

Clinicopathological features and genomic profiles of a group of secretory breast carcinomas in which progressive cases have more complex genomic features.

BACKGROUND: Secretory breast carcinoma (SBC) is a rare malignant breast neoplasm with distinct histological features, including solid, microcystic, tubular, and rarely papillary structures, traditionally characterized by a t (12;15) (p13:q25) translocation, which usually leads to ETV6-NTRK3 fusion, suggesting an early event in tumorigenesis. Due to the rarity of this disease, very few genome sequencing studies have been performed on a series of cases, especially progressive cases. METHODS: Seven lesions from 5 patients diagnosed at the Third Affiliated Hospital of Soochow University from 2007 to 2021 were included. Clinicopathological features and prognosis/survival data were collected. Next-generation DNA sequencing was performed on six of the seven lesions. RESULTS: In total, 3/7 (42.9%) lesions demonstrated estrogen receptor (ER) expression, including weak, moderate to strong staining, and no lesion demonstrated progesterone receptor (PR) expression. There were no cases of human epidermal growth factor (HER2) overexpression, and the Ki-67 index was low. S-100 and pan-TRK protein were diffusely positively expressed in all cases. All lesions were characterized by a t(12;15) (p13:q25) translocation, leading to ETV6-NTRK3 fusion confirmed by fluorescence in situ hybridization (FISH). The sequencing results showed that ETV6-NTRK3 fusion was the main driver of early tumorigenesis, while SBC with invasive biological behavior had more complex genomic variation in which TERT promoter mutation was detected. CONCLUSIONS: Immunohistochemical staining of a biomarker panel, including ER, PR, HER2, Ki-67, S-100 and pan-TRK, can be used as an auxiliary diagnostic tool, and FISH detection can be used as a diagnostic tool. ETV6-NTRK3 gene fusion involving multiple sites may drive tumorigenesis, while mutations in the TERT promoter region may be a factor driving tumor progression.

Genomic characteristics of two breast malignant phyllodes tumors during pregnancy and lactation identified through whole-exome sequencing.

BACKGROUND: The genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations. METHODS: DNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes. RESULTS: In total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1. CONCLUSION: Our study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.

Novel myeloma patient-derived xenograft models unveil the potency of anlotinib to overcome bortezomib resistance.

Multiple myeloma (MM) remains a common hematologic malignancy with a 10-year survival rate below 50%, which is largely due to disease relapse and resistance. The lack of a simple and practical approach to establish myeloma patient-derived xenograft (PDX) hampers translational myeloma research. Here, we successfully developed myeloma PDXs by subcutaneous inoculation of primary mononuclear cells from MM patients following series tumor tissue transplantations. Newly established myeloma PDXs retained essential cellular features of MM and recapitulated their original drug sensitivities as seen in the clinic. Notably, anlotinib therapy significantly suppressed the growth of myeloma PDXs even in bortezomib-resistant model. Anlotinib treatments polarized tumor-associated macrophages from an M2- to an M1-like phenotype, decreased tumor vascular function, and accelerated cell apoptosis in myeloma PDXs. Our preclinical work not only unveiled the potency of anlotinib to overcome bortezomib resistance, but also provided a more practical way to establish MM PDX to facilitate myeloma research.

Evaluating the Histopathology of Pancreatic Ductal Adenocarcinoma by Intravoxel Incoherent Motion-Diffusion Weighted Imaging Comparing With Diffusion-Weighted Imaging.

OBJECTIVES: To explore the differences between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion-weighted imaging (DWI) in evaluating the histopathological characters of pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study enrolled 50 patients with PDAC confirmed by pathology from December 2018 to May 2020. All patients underwent DWI and IVIM-DWI before surgeries. Patients were classified into low- and high-fibrosis groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), false diffusion coefficient (D*), and perfusion fraction (f) were measured by two radiologists, respectively in GE AW 4.7 post-processing station, wherein ADC values were derived by mono-exponential fits and f, D, D* values were derived by biexponential fits. The tumor tissue was stained with Sirius red, CD34, and CK19 to evaluate fibrosis, microvascular density (MVD), and tumor cell density. Furthermore, the correlation between ADC, D, D*, and f values and histopathological results was analyzed. RESULTS: The D values were lower in the high-fibrosis group than in the low-fibrosis group, while the f values were opposite. Further, no statistically significant differences were detected in ADC and D* values between the high- and low-fibrosis groups. The AUC of D and f values had higher evaluation efficacy in the high- and low-fibrosis groups than ADC values. A significant negative correlation was established between D values, and fibrosis and a significant positive correlation were observed between f values and fibrosis. No statistical difference was detected between DWI/IVIM parameters values and MVD or tumor cell density except for the positive correlation between D* values and tumor cell density. CONCLUSIONS: D and f values derived from the IVIM model had higher sensitivity and diagnostic performance for grading fibrosis in PDAC compared to the conventional DWI model. IVIM-DWI may have the potential as an imaging biomarker for predicting the fibrosis grade of PDAC.

Ikaros is heterogeneously expressed in lung adenocarcinoma and is involved in its progression.

OBJECTIVE: The aim of the present study was to assess the expression of the Ikaros transcription factor (IKZF1) in lung adenocarcinoma and investigate whether expression levels of Ikaros are correlated with lung adenocarcinoma progression. METHODS: We conducted a retrospective study of 325 cases of resected stage I pulmonary adenocarcinoma, in which histological subtyping was performed according to the 2015 World Health Organization classification. We performed immunohistochemical examinations to assess expression of Ikaros in pulmonary adenocarcinomas and evaluated the correlation between Ikaros expression and cancer progression. RESULTS: Immunohistochemical staining was heterogeneous, with the majority of well-differentiated and moderately differentiated lung adenocarcinomas being weakly positive and the majority of the poorly differentiated lung adenocarcinomas exhibiting strong positive staining. Higher expression of Ikaros was associated with tumor recurrence or metastasis. CONCLUSIONS: Ikaros is heterogeneously expressed in different subtypes of lung adenocarcinoma; higher expression of Ikaros was found to be associated with cancer progression.

Apolipoprotein M inhibits proliferation and migration of larynx carcinoma cells.

Prior studies have shown that apolipoprotein M (APOM) is involved in the development of some cancers. Here we investigated the effects of APOM on larynx cancer (LC). 20 patients with vocal cord polyps and 18 patients with LC were included in this study. The protein and mRNA levels of the samples were analysed using the Wes-ProteinSimple system (or traditional Western blot) and PCR technology, respectively. APOM protein level in cancer tissues was lower than that in paracarcinomatous (P = 0.0003) and polyp tissues (P < 0.0001). APOM overexpression significantly inhibited TU686 cell proliferation (P < 0.0001) and migration (P < 0.01), and increased expression of vitamin D receptor (VDR, P < 0.0001) as well as nuclear factor erythroid 2-like 3 (NFE2L3, P = 0.0215). In addition, matrix metalloproteinase-10 (MMP-10) mRNA level was significantly reduced in the APOM overexpression group (P = 0.0077). However, Western blot analysis showed that APOM overexpression did not change VDR, NFE2L3 and MMP-10 protein levels (P > 0.05). In summary, APOM inhibits the proliferation and migration of LC cells, but may not be related to VDR, NFE2L3 and MMP-10, which needs further study.

The High Level of Tertiary Lymphoid Structure Is Correlated With Superior Survival in Patients With Advanced Gastric Cancer.

Background: A tertiary lymphoid structure (TLS) is a crucial component of the tumor microenvironment, which reflects the anti-tumor immune response in the host. The aim of the present study was to carry out a histopathological evaluation for TLS and assess its prognostic value in gastric cancer (GC). Methods: A total of 1,033 cases that have received a gastrectomy were reviewed, including 914 in the primary cohort and 119 in the validation cohort. TLS was assessed by optical microscopy and verified by immunohistochemistry. A total of five histopathological evaluation methods were compared in the primary cohort and validated in the validation cohort. In addition, MECA-79 and CD21 were used to verify the accuracy of the histopathological scoring system for TLS. The association among TLS, clinicopathological parameters, and patient prognosis was analyzed. Results: TLS as assessed by morphology and immunohistochemistry were significantly correlated and consistent. The morphological evaluation of TLS was accurate. Typically, the high level of TLS was significantly correlated with tumor size (P = 0.047), histological grade (P = 0.039), pTN stage (P = 0.044), and WHO subtype (P < 0.001). In addition, TLShi was a positive indicator of overall survival, as determined by Kaplan-Meier survival (P = 0.038) and multivariate Cox regression analyses (hazard ratio = 0.794, 95% CI: 0.668-0.942, P = 0.008). According to the results, TLShi had a positive effect on the primary cohort patients with pTN stages II and III (P = 0.027, P = 0.042). Conclusions: The histopathological evaluation of TLS was accurate. Diagnosis based solely on hematoxylin and eosin staining of the sections did not easily distinguish tumor-associated TLS. The density of TLS in the center of the tumor was found to be more indicative of patient prognosis than TLS in the invasive margin, with the levels of total TLS shown to best correlate with overall survival in patients with advanced-stage GC.

CD8+ T cells located in tertiary lymphoid structures are associated with improved prognosis in patients with gastric cancer.

The presence of tumor infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissues are of great prognostic significance in several types of human cancer. The present study investigated the density of TILs and TLSs in gastric cancer (GC) tissues and their association with pathological parameters. Moreover, the clinical significance of follicular CD8+ cytotoxic T cells present within the germinal centers of the tumor-associated TLSs was investigated. Immunohistochemistry and H&E staining were used to examine the infiltration and distribution patterns of TILs, TLSs and germinal center (gc) CD8+ TILs in tumor tissues obtained from 63 patients with GC. The number of TILs, TLSs, combination of TILs and TLSs (TILs-TLSs) and gcCD8+ TILs were used to define tumoral immune parameters, and the prognostic value of these parameters was assessed. The analysis revealed that patients with GC with increased levels of TILs, TLSs, or gcCD8+ TILs exhibited improved overall survival. In addition, gcCD8+ TILs levels were significantly associated with patient age, histological grade and pTN stage. Increased levels of TILs-TLSs were positively associated with nerve invasion, tumor thrombus, nodal metastasis and histological grade. Multivariate Cox regression analysis revealed that TILs-TLSs and gcCD8+ TILs were independent prognostic factors. The data obtained in the present study demonstrated that high levels of tumoral immune parameters are important independent prognostic predictors for human GC. The results also suggested a possible role of gcCD8+ TILs in tumor immune surveillance.

Intratumoral Macroscopic Fat and Hemorrhage Combination Useful in the Differentiation of Benign and Malignant Solid Renal Masses.

To evaluate the value of combining the detection of intratumoral macroscopic fat and hemorrhage in the differentiation of the benign from malignant solid renal masses.Conventional magnetic resonance imaging (MRI), chemical shift (CS)-MRI, and susceptibility-weighted imaging were performed in 152 patients with 152 solid renal masses, including 48 benign and 104 malignant masses all pathologically confirmed. The presence of macroscopic fat detected by CS-MRI and hemorrhage detected by susceptibility-weighted imaging were evaluated in all masses. The rates of macroscopic fat and hemorrhage observed between benign and malignant masses were compared by a χ test. All masses found to contain macroscopic fat with or without hemorrhage were considered to be benign. The remaining masses (without macroscopic fat) found not to contain hemorrhage were considered to be benign. Only those found to contain hemorrhage alone were considered to be malignant. The evaluation indexes for differentiating and forecasting the benign and malignant masses were calculated.Significant differences in the rate of macroscopic fat (observed in 85.42% of benign masses vs. 0% of malignant masses) and hemorrhage (observed in 4.17% of benign masses vs. 95.19% of malignant masses) were measured in the benign and malignant groups (P < 0.005, for both). The 41 masses containing macroscopic fat with or without hemorrhage and 11 masses containing neither macroscopic fat nor hemorrhage were considered to be benign. The 100 masses containing no macroscopic fat and only hemorrhage were considered to be malignant. By combining the results for the macroscopic fat and hemorrhage, the accuracy, sensitivity, and specificity in the differential diagnosis of the benign and malignant masses were 96.05%, 95.19%, and 97.92%, respectively, and the accuracy and error rate of forecasting the benign and malignant masses were 95.39% and 4.61%, respectively.Combining the detection intratumoral macroscopic fat and hemorrhage can be used to differentiate the benign from malignant solid renal masses.

Epigenetic inhibition of miR-663b by long non-coding RNA HOTAIR promotes pancreatic cancer cell proliferation via up-regulation of insulin-like growth factor 2.

Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Although microRNAs are involving in the carcinogenesis and development of pancreatic cancer, little information is known regarding the role of miR-663b in pancreatic cancer. In this study, the expression of miR-663b in pancreatic cancer cells was down-regulated by hypermethylation in its putative promoter region, and overexpression of miR-663b repressed cell proliferation, invasion and migration, and induced apoptosis in pancreatic cancer cells. Bioinformatics analysis, luciferase report assay and rescue experiments showed that insulin-like growth factor 2 (IGF2) was a direct target of miR-663b. Results from clinical samples showed that the expression level of miR-663b correlated with the pathological grading, and the expression of miR-663b was down-regulated and was inversely correlated with IGF2 expression level in pancreatic cancer tissues. More importantly, the long non-coding RNA, HOX transcript antisense RNA (HOTAIR), was up-regulated in both pancreatic cancer cells and tissues, and HOTAIR suppressed the expression of miR-663b in pancreatic cancer by histone modification on H3K4me3 and H3K27me3 on miR-663b promoter. Further in vivo studies demonstrated that the stable overexpression of miR-663b or knock-down of HOTAIR inhibited tumor growth and was associated with IGF2 expression. In summary, our studies demonstrated that miR-663b is epigenetically repressed by HOTAIR and exerts its tumor-suppressive function via targeting IGF2 in pancreatic cancer.

Primary lymphoepithelioma-like carcinoma of salivary glands: a clinicopathological study of 21 cases.

Lymphoepithelioma-like carcinoma (LELC) of salivary glands is a rare kind tumor. In this study, the authors evaluated 21 patients with LELC of salivary glands who had long-term follow-up. Clinical characteristics, Epstein-Barr virus (EBV) infection, immunohistochemical features, oncoprotein expression, treatments, and outcomes were analyzed. All patients were Chinese. Their ages ranged from 20 to 73 years. All tumors showed the typical syncytial growth pattern of undifferentiated epithelial cells with a significant lymphocyte reaction. All of patients were found by in situ hybridization to have the EBV genome. All tumors showed positive immunostaining of AE1/AE3, CK5/6 and p63. Nearly all cases had bcl-2 oncoprotein expression, but the detection rate of p53, and c-erb B-2 expression was extremely low. LELC of salivary glands is a distinct entity of salivary cancer. LELC of salivary glands can receive multimodality treatment and has a better prognosis similar to that of nasopharyngeal carcinoma.

The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells.

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

Preoperatively evaluating the correlation between pathological grades and blood oxygenation level-dependent MRI in clear cell renal cell carcinomas.

RATIONALE AND OBJECTIVES: To assess whether r(2)* values can be used to determine the nuclear grade of clear cell renal cell carcinomas (CRCC). MATERIALS AND METHODS: A total of 26 patients with pathologically proven CRCCs underwent blood oxygen level-dependent magnetic resonance imaging. r(2)* values were determined for the solid components of CRCC lesions. Histological nuclear grade was determined for each lesion. All patients were divided into low- and high-grade groups. r(2)* values were compared between different grades and between low- and high- grade groups. Receiver operating characteristic curve was drawn to establish the cutoff point for r(2)* values. The correlation between r(2)* values and pathological groups was assessed. RESULTS: Low-grade group (grades I + II) contained 17 cases and high-grade group (grades III + IV) contained nine cases. The intraclass correlation coefficient for r(2)* values was 0.89. Significant difference was seen between different grades (P < .005). r(2)* values of the high-grade group were higher than the low-grade group (P < .005). A sensitivity of 78% and a specificity of 100% were achieved with a cutoff of 31.87 seconds(-1). r(2)* values directly correlated with pathological groups (P < .005). CONCLUSION: r(2)* values of CRCCs could be employed as a noninvasive biomarker to help classify the nuclear grade of CRCC.