Identification of the novel allele, HLA-B*15:388, in a Chinese bone marrow donor.

The novel allele, HLA-B*15:388, was identified in a Chinese bone marrow donor by sequence-based typing.

Effects of individual and partner factors on anxiety and depression in Taiwanese prostate cancer patients: A longitudinal study.

Studies exploring the mediating and predictive factors of anxiety and depression for prostate cancer patients in Eastern countries are scant. Guided by the transactional model of stress and coping, this study determined the predictors and mediators of anxiety and depression in prostate cancer patients. The participants comprised 115 prostate cancer patients and 91 partners. The patients and partners completed questionnaires regarding physical symptoms, disease appraisals, coping behaviours, anxiety and depression in the period before confirmation of treatment decisions and 1, 3, 6 and 12 months after treatment. The results revealed that partner anxiety engendered a stressful situation and aggravated patient anxiety. Patients' threat appraisals and affective-oriented coping behaviours mediated the relationships between their anxiety levels and those of their partners. The patients' most recent prostate-specific antigen (PSA) levels and hormonal symptoms were key predictors of their anxiety and depression levels. The patients' harm appraisals mediated the relationships between their most recent PSA levels and hormonal symptoms and depression. Their threat appraisals and affective-oriented coping behaviours mediated the relationships between their hormonal symptoms and anxiety and depression. To manage those key factors, reframing, appraising disease and improving coping behaviours may reduce anxiety and depression levels in prostate cancer patients.

A novel HLA-B allele, HLA-B*35:348, was identified by sequencing-based typing.

HLA-B*35:348 has 1 nucleotide substitution, c.817G > C (GTG→CTG at codon 248) compared with B*35:01:01:01.

The novel allele, HLA-A*24:383, was identified in a Chinese individual by sequence-based typing.

HLA-A*24:383 differs HLA-A*24:02:01:01 by one nucleotide substitution from C to G in exon 4, position 755.

A novel HLA class II allele, HLA-DRB1*04:01:17, identified in a Chinese volunteer donor for China Marrow Donor Program.

One nucleotide replacement at nucleotide 144 of HLA-DRB1*04:01:01 results in a new allele, HLA-DRB1*04:01:17.

A novel HLA-B allele, HLA-B*13:91, was identified by sequencing-based typing in the CMDP.

The new allele HLA-B*13:91 was initially identified in a Chinese individual by sequence-based typing.

Identification of the novel HLA-B*15:02:11 allele in a Chinese individual.

The novel allele B*15:02:11, was identified in a Chinese individual by sequence-based typing.

CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence.

Transforming growth factor-α (TGF-α)-induced proliferation and transforming growth factor-ß (TGF-ß)-mediated quiescence are intricately balanced in normal lung-tissue homeostasis but are deregulated during neoplastic progression of lung cancer. Here, we show that Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a novel MYC-interacting transcriptional modulator, responds to TGF-α induction and TGF-ß suppression to orchestrate cellular proliferation and quiescence, respectively. Upon TGF-α induction, CITED2 was induced by MYC and further modulated MYC-mediated transcription in a feed-forward manner. CITED2 recruited p300 to promote MYC-p300-mediated transactivation of E2F3, leading to increased G1/S cell cycle progression. Moreover, CITED2 inhibited cellular quiescence by enhancing MYC-mediated suppression of p21(CIP1). CITED2 interacted with histone deacetylase 1 (HDAC1) and potentiated MYC-HDAC1 complex formation. TGF-ß stimulation provoked downregulation of CITED2, which abrogated MYC-HDAC1-mediated p21(CIP1) suppression, causing cellular quiescence. Ectopic CITED2 expression enhanced tumor growth in nude mice; furthermore, CITED2 knockdown caused tumor shrinkage and increased overall host mouse survival rates. Expression of CITED2/MYC/E2F3/p21(CIP1) signaling molecules was associated with poor prognosis of lung cancer patients. Thus, CITED2 functions as a molecular switch of TGF-α and TGF-ß-induced growth control, and MYC-CITED2 signaling axis provides a new index for predicting clinical outcome.

A simple renal cyst invaded by infiltrating urothelial carcinoma mimicking a Bosniak Class IV renal cyst.

We report a 79-year-old woman with a left side simple renal cyst invaded by infiltrating urothelial carcinoma mimicking a Bosniak Class IV renal cyst. Computerized tomography has high accuracy for the diagnosis of renal cysts and urothelail carcinoma. But, in this case it was still difficult to distinguish a simple renal cyst with infiltrating urothelial carcinoma invasion from a Bosniak Class IV renal cyst on CT scan. The management of a Bosniak Class IV renal cyst and urothelail carcinoma is totally different. Therefore, we performed a left side nephroureterectomy. This patient will have regular follow-up with cystoscopy every 3 months for the first 2 y, every 6 months for the next 2 y, and then annually thereafter.

Expression of parvin-beta is a prognostic factor for patients with urothelial cell carcinoma of the upper urinary tract.

BACKGROUND: Parvin-beta (ParvB), a potential tumour suppressor gene, is a focal adhesion protein. We evaluated the role of ParvB in the upper urinary tract urothelial cell carcinoma (UUT-UC). METHODS: ParvB mRNA and proteins levels in UUT-UC tissue were investigated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. In addition, the expression of ParvB in tissues from patients with UUT-UC at different stages was evaluated by immunohistochemistry. Furthermore, biological functions of ParvB in urothelial cancer cells were investigated using a doxycycline-inducible overexpression system and siRNA. RESULTS: Western blot and mRNA analysis showed downregulation of ParvB expression in frozen UUT-UC tissue. Immunohistochemistry revealed high staining intensity of ParvB in normal urothelium, which decreased markedly at advanced stages of UUT-UC (P=0.0000). Moreover, ParvB was an independent prognostic indicator for disease-specific survival of patients with UUT-UC. Functional assays indicated that overexpression of ParvB in an urothelial cancer cell line resulted in decreased cell growth rate and ability to migrate. In contrast, knockdown of ParvB expression increased cell migration ability. CONCLUSIONS: Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration. Downexpression of ParvB level in UUT-UC correlated with tumour stage, and was an independent unfavourable prognostic factor for disease-specific survival of patients with UUT-UC.

Ezrin mediates c-Myc actions in prostate cancer cell invasion.

The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals involve the modulation of Akt and GSK-3beta activity resulting in increased c-Myc protein synthesis and inhibition of its degradation. In summary, we have shown a key role for ezrin as a mediator of c-Myc-induced tumorigenesis in prostate cancer cells.

Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy.

BACKGROUND: Hand-foot skin reaction is a distinctive cutaneous side-effect of antineoplastic kinase inhibitor-targeted therapy. Severe hand-foot skin reaction requires postponement of treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable. OBJECTIVES: To report the clinical and histopathological findings of hand-foot skin reaction produced by the multikinase inhibitor sorafenib. METHODS: Nine patients with metastatic carcinoma-seven with renal cell carcinoma (RCC), one with melanoma and one with hepatocellular carcinoma (HCC)-received continuous, oral sorafenib 400 mg twice daily. Hand-foot skin reaction was defined and graded according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies from lesions of erythematous scaly or blistering skin were obtained from five cases (four RCC and one HCC). RESULTS: Seven of the nine (78%) patients developed hand-foot skin reaction characterized by well-demarcated, tender, erythematous papules and plaques with greyish blisters or hyperkeratotic, callus-like formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand-foot skin reaction lesions revealed epidermal acanthosis, papillomatosis, parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar degeneration. Other skin toxicities included angular cheilitis, seborrhoeic dermatitis and perianal dermatitis. CONCLUSIONS: The clinical manifestations and histopathological features of sorafenib-induced skin reactions are unique. The most relevant histopathological findings of hand-foot skin reaction include keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic bodies, and intraepidermal blisters in the stratum malpighii. Further studies are warranted to elucidate the mechanisms of this novel multitargeted kinase inhibitor-associated skin reaction.

Androgens induce CD-9 in human prostate tissue.

Based on microarray analyses of LNCaP and LNCaP-r prostatic cell-lines we tentatively identified CD-9 as an androgen sensitive protein. This prompted us to characterize the androgen sensitivity and the correlation to malignancy of CD-9 at the protein level. Using Western blot, RT-PCR and immunohistochemistry the expression of CD-9 was analysed in LNCaP cells stimulated during increasing time by the synthetic androgen R1881 and also in 88 specimens of human prostate cancer tissues. Expression of CD-9 was induced by R1881 in LNCaP. CD-9 was immunolocalized in human prostate tissue sections representing non-malignant tissue as well as tumour areas. In non-malignant glands CD-9 immunoreactivity was observed at the apical and lateral cell borders of luminal epithelial cells. Basal epithelial cells were largely unstained. In tumour areas CD-9 staining intensity was variable and apparently not related to primary Gleason grade. In prostate tissue from a patient under androgen ablation therapy no staining was observed in luminal epithelial cells or in the tumour areas, but some staining was observed in basal epithelial cells. CD-9 is regulated by androgens in LNCaP and present in human prostate specimens. The expression is variable and changes in expression levels. These and earlier studies using other tissues indicate that CD-9 and its cellular localization could have an important role in prostate cancer cell development.

Gain of 17q in malignant fibrous histiocytoma is associated with a longer disease-free survival and a low risk of developing distant metastasis.

In this study, a panel of 39 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterised for chromosomal alterations. The results were then evaluated in relation to the survival and the occurrence of recurrent disease during follow-up for an average period of 63 months. Chromosomal alterations detected by comparative genomic hybridisation (CGH) were recorded in 37 of the 39 cases analysed. The most frequent CGH abnormalities were gains of 17p, 20q, 16p, 17q, 1p31, 7q21, and 9cen-q22, and losses of 9p21-pter and 13q21-22. However, the patterns of CGH imbalances did not allow the identification of a single common event, suggesting that the key initiating event(s) is not a numerical imbalance. Patients with tumours harbouring a gain of 17q showed significantly longer overall and disease-free survival (P=0.001 and 0.008) as well as lower frequency of metastasis (P=0.018) during follow-up. Taken together, the findings suggest that the clinical outcome of MFH is associated with the genetic profiles of the primary tumours. Importantly, a subgroup of MFHs characterised by a low risk of developing metastasis and local recurrence is recognised based on their frequent gains of 17q by CGH.