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1.
Objective: This study was conducted to evaluate a computer program named Help with Adjustment to Alopecia by Image Recovery (HAAIR) that was developed to provide educational support and reduce distress in women with hair loss following chemotherapy. Methods: Forty‐five women who had been diagnosed with cancer and anticipated alopecia following treatment were randomly assigned to either the Imagining group (IG) or Standardized Care group (SCG). Patients in the IG used a computer‐imaging program that created the patient's image on a screen to simulate baldness and use of wigs whereas patients in the SCG were directed to a resource room at the Cancer Center established for women with chemotherapy‐related alopecia. Assessment data using the Brief Symptom Inventory, Importance of Hair Questionnaire, and the Brief Cope were completed at baseline (T1), before chemotherapy and hair loss, following hair loss (T2), and 3 months follow‐up (T3). Results: All women were able to successfully use the touch screen computerized‐imaging program and reported that using the computer was a positive, helpful experience, thus establishing acceptability and usability. Women in both the IG and the SCG group showed significantly lower hair loss distress scores at T2 after hair loss than at T1 with T3 distress scores increasing in the SCG and decreasing in the IG. Those with avoidance coping reported more distress. Conclusions: This evaluation demonstrates that the HAAIR program is a patient‐endorsed educational and supportive complement to care for women facing chemotherapy‐related alopecia. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

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Objective: Total or partial nasal amputation following tumour resection is one of the more severe facial disfigurements. Successful nasal reconstruction can therefore be regarded as restoring a patient's psychosocial health. The objective of this study, therefore, was to evaluate different determinants of patient's psychosocial functioning and their effect on patient satisfaction after nasal reconstruction. Methods: A cross‐sectional study with a case–control study design was conducted. Level of satisfaction with nasal appearance and psychosocial functioning were assessed with validated questionnaires. Results: A total of 30 consecutive patients were recruited. They were treated between November 2001 and May 2005 for (sub)total nasal defects following radical tumour resection. For the control group 99 consented to participate. Social anxiety and avoidance were scored significantly higher within the patient group (p=0.01). Patients cope significantly more passive than controls (p=0.04). Self‐esteem levels did not differ significantly between patients and controls (p=0.22). Determinants of satisfaction with nasal reconstruction were self‐esteem (p=0.0001), active coping strategy (p=0.001), and passive coping strategy (p=0.0001). Conclusion: Nasal reconstruction has an impact on psychosocial functioning of nasal reconstruction patients. In addition, self‐esteem and coping strategy are important determinants of satisfaction with nasal reconstruction, and should be held in mind when treating a patient. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   

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Receptor tyrosine kinase MET (c‐MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c‐MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET‐related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty‐nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET‐related molecules. Four c‐MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c‐MET and p‐MET. The variants of MET were not associated with c‐MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c‐MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET‐negative subgroups. Except tivantinib, the c‐MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c‐MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well‐characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET‐related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c‐MET inhibitors.  相似文献   

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Veliparib (ABT‐888) is a potent, orally bioavailable poly(ADP‐ribose) polymerase‐1 and ‐2 inhibitor. This phase 1 study evaluated the tolerability, pharmacokinetic profile, safety, and preliminary antitumor activity of single‐agent veliparib in Japanese patients with advanced solid tumors. Eligible patients were assigned to treatment with veliparib at 200 or 400 mg dose; veliparib was self‐administered orally twice daily on days 1–28 of 28‐day cycles. Dose escalation, following a 3 + 3 design, defined dose‐limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose. Sixteen patients were enrolled (median age, 59 years). Fourteen patients had high‐grade serous ovarian cancer, one had primary peritoneal cancer, and one had BRCA‐mutated breast cancer. The most frequent treatment‐emergent adverse events were nausea and vomiting (93.8% each), decreased appetite (62.5%), abdominal pain, diarrhea, and malaise (31.3% each). A grade ≥3 toxicity was observed in 50% of patients; one patient each in the 200 mg (n = 4) and 400 mg (n = 12) cohorts experienced serious adverse events. Dose‐limiting toxicities were observed for one patient at the 400 mg dose. No toxicities leading to death were reported. The recommended phase 2 dose was defined as 400 mg twice daily. The veliparib pharmacokinetic profile was consistent with that reported for the Western population. Two patients, both with ovarian cancer, had a RECIST partial response. Veliparib monotherapy showed manageable tolerability and safety profiles and a predictable pharmacokinetic profile at a 400 mg twice‐daily dose, and supports the inclusion of Japanese patients in the multinational phase 3 study (NCT02470585).  相似文献   

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Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient‐derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient‐specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high‐risk neuroblastoma in patients. PDX‐derived cells were cultured in serum‐free medium where they formed free‐floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour‐initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK‐N‐BE(2)c cell line‐derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high‐risk metastatic neuroblastoma.  相似文献   

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Adoptive transfer of donor‐derived cytolytic T‐lymphocytes (CTL) has evolved as a promising strategy to improve graft‐versus‐leukemia (GvL) effects in allogeneic hematopoietic stem‐cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)‐reactive CD8+ CTL with central and effector memory phenotype in a new allogeneic donor‐patient specific humanized mouse model. CTL lines and clones obtained upon stimulation of naive CD45RA+ donor CD8+ T cells with either single HLA antigen‐mismatched or HLA‐matched primary AML blasts, respectively, elicited strong leukemia reactivity during cytokine‐optimized short to intermediate (i.e., 2–8 weeks) culture periods. Single doses of CTL were intravenously infused into NOD/scidIL2Rcgnull mice when engraftment with patient AML reached bone marrow infiltration of 1–5%, clinically defining minimal residual disease status. This treatment resulted in complete regression of HLA‐mismatched and strong reduction of HLA‐matched AML infiltration, respectively. Most importantly, mice receiving AML‐reactive CTL showed significantly prolonged survival. Transferred CTL were detectable in murine bone marrow and spleen and demonstrated sustained AML‐reactivity ex vivo. Moreover, injections with human IL‐15 clearly promoted CTL persistence. In summary, we show that naive donor‐derived CD8+ CTL effectively combat patient AML blasts in immunodeficient mice. The donor‐patient specific humanized mouse model appears suitable to evaluate therapeutic efficacy of AML‐reactive CTL before adoptive transfer into patients. It may further help to identify powerful leukemia rejection antigens and T‐cell receptors for redirecting immunity to leukemias even in a patient‐individualized manner.  相似文献   

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Improved treatment outcomes for the endometrial cancer patient requires precision methods to investigate the biology of this disease and clinically relevant models to test treatment drugs. Hence, we applied a personalized platform to investigate whether in vitro and in vivo models could accurately predict effective treatment regimens. We successfully expanded ascites‐derived tumor cells from an endometrial cancer patient with malignant ascites using ascites collected prior to chemotherapy treatment. Hematoxylin–eosin and immunohistochemistry staining of ascites‐derived tumor cells confirmed the source of endometrial cancer cells. Ascites‐derived tumor cells were sensitive to cisplatin and doxorubicin single‐agent treatments in CCK‐8 assay and 3‐D culture, a condition that more closely mimics the in vivo environment. We further showed that ascites‐derived tumor cells from this patient could form tumors in NOD/SCID mice with preserved morphological characteristics. A remarkable concordance between the clinical response of cisplatin and the results of in vitro and in vivo drug tests reflected the reliability of our personalized approach in this case. Together, our results indicated that an effective platform for ex vivo and in vivo culture of ascites‐derived tumor cells from our endometrial cancer patient could be applied to identify treatment options, and may be commonly used in treating cancer patients with malignant ascites in the future.  相似文献   

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Anticancer agent‐incorporating polymeric micelles accumulate effectively in tumors via the enhanced permeability and retention effect to exert potent antitumor effects. However, combined use of such micelles has not been elucidated. We compared the effect of combining the epirubicin‐incorporating micelle NC‐6300 and 1,2‐diaminocyclohexane platinum (II) (oxaliplatin parent complex)‐incorporating micelle NC‐4016 (NCs) with that of epirubicin and oxaliplatin (E/O) in 44As3Luc cells using the combination index method. The in vivo antitumor activities of NCs and E/O were evaluated in mice bearing 44As3Luc xenografts. Pharmacokinetic analysis was performed by high‐performance liquid chromatography and mass spectrometry. Cardiotoxicity of NC‐6300 and epirubicin was assessed by echocardiography. Neurotoxicity of NC‐4016 and oxaliplatin was evaluated by examining the paw withdrawal response to noxious mechanical stimuli. NCs showed a highly synergistic activity equivalent to E/O. In vivo, NCs exhibited higher antitumor activity in the subcutaneous tumor model and longer overall survival in the orthotopic tumor model than E/O (p < 0.001, p = 0.015, respectively). The intratumor concentrations of epirubicin and platinum were significantly higher following NCs than following E/O administration. Moreover, the micelles showed lower cardiotoxicity and neurotoxicity than the corresponding conventional drugs. The combined use of the micelles was associated with remarkable efficacy and favorable toxicities in the human gastric cancer model, and warrants the conduct of clinical trials.  相似文献   

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Candida auris is an emerging multidrug‐resistant yeast associated with invasive infection in healthcare settings. Recently, C auris cases in the United States have been detected in 11 states with the majority of cases in New York, New Jersey and Illinois. Rapid and accurate identification of C auris is critical for patient care and the implementation of public health measures to control the spread of infection. Our aim was to develop and validate a rapid DNA extraction method using the Roche MagNA Pure 96 instrument and a TaqMan real‐time PCR assay for reliable, high‐throughput identification of C auris. We evaluated 247 patient dermal swab samples previously analysed by culture/MALDI‐TOF. The diagnostic sensitivity and specificity were 93.6% and 97.2%, respectively. The assay was highly reproducible with a detection limit of 1 C auris CFU/10 μL. A receiver operating characteristic curve analysis of the real‐time PCR data showed an area of 0.982 under the curve, with a CT cut‐off value of ≤37.0. The turnaround time from DNA extraction to real‐time PCR results was approximately 200 samples/day. In conclusion, we successfully validated a rapid and high‐throughput method for accurate and reproducible identification of C auris with a significantly reduced turnaround time compared to culture/MALDI‐TOF based methods.  相似文献   

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BARTLETT Y.K., SELBY D.L., NEWSHAM A., KEDING A., FORMAN D., BROWN J., VELIKOVA G. & WRIGHT P. (2012) European Journal of Cancer Care Developing a useful, user‐friendly website for cancer patient follow‐up: users' perspectives on ease of access and usefulness UK cancer survival has improved, leading to an increase in review patients and pressure on clinics. Use of the Internet for information exchange between patients and healthcare staff may provide a useful adjunct or alternative to traditional follow‐up. This study aimed to develop and evaluate a website for use in follow‐up cancer care in terms of usability, feasibility and acceptability. A website was developed and underwent iterative amendment following patient usability testing in focus groups. Patients on follow‐up completed a Computer and Internet Usage Questionnaire. Internet users consented to a randomised crossover study to complete paper and online questionnaires, browse the website and participate in a website evaluation interview. Patient website use was tracked. Usability: Website changes were made following patient testing (n= 21). Patients would have liked a ‘personalized’ website with links to their clinical team, out with the scope of this study. Feasibility: The majority of participants (65%) had Internet access. Age remained a differentiating factor. Acceptability: Final evaluation (n= 103) was positive although many would like to maintain face‐to‐face hospital contact. User involvement in website design can ensure patient needs are met. A website model for follow‐up will suit some patients but others will prefer clinical contact.  相似文献   

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We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second‐generation, enhanced‐selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B‐cell non?Hodgkin lymphoma (B‐cell NHL) and chronic lymphocytic leukemia (CLL). This was an open‐label, multicenter, phase I study. Seventeen patients (male N = 8) with a median age of 70 years were enrolled in 4 dose cohorts (160 mg once daily [N = 3], 320 mg once daily [N = 3], 480 mg once daily [N = 4] and 300 mg twice daily [N = 7]); 4 patients had continued tirabrutinib administration as of 4 January 2018. The maximum tolerated dose was not reached. Pneumonitis (N = 1) was the dose‐limiting toxicity for 300 mg twice daily. Common adverse events (AEs) were rash (35.3%) and vomiting (29.4%). Eight patients (47.1%) developed grade ≥3 AEs: neutropenia (23.5%), anemia (11.8%) and leukopenia (11.8%) were frequent. The overall response rate (≥PR) was 76.5% (13/17 patients), including 4 DLBCL patients with no CD79A/B or MYD88 mutations, and 1 CLL patient with a TP53 mutation, providing promising data for future developments. Of 16 patients with measurable lesions during the screening period, 12 showed ≥50% reductions in tumor diameter. In many patients, the tumor size decreased soon after beginning treatment. The maximum serum concentration for tirabrutinib was 611, 1220, 1280 and 886 ng/mL on Day 1 and 484, 971 1940, and 961 ng/mL on Day 28 for Cohorts 1‐4, respectively. Tirabrutinib pharmacokinetics were linear, with little accumulation following multiple doses. Tirabrutinib was well tolerated and showed promising efficacy for B‐cell NHL/CLL.  相似文献   

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It has recently been reported that a large proportion of human malignant pleural mesothelioma (MPM) cell lines and patient tissue samples present high expression of the c‐MYC oncogene. This gene drives several tumorigenic processes and is overexpressed in many cancers. Although c‐MYC is a strategic target to restrain cancer processes, no drugs acting as c‐MYC inhibitors are available. The novel thienotriazolodiazepine small‐molecule bromodomain inhibitor OTX015/MK‐8628 has shown potent antiproliferative activity accompanied by c‐MYC downregulation in several tumor types. This study was designed to evaluate the growth inhibitory effect of OTX015 on patient‐derived MPM473, MPM487 and MPM60 mesothelioma cell lines and its antitumor activity in three patient‐derived xenograft models, MPM473, MPM487 and MPM484, comparing it with cisplatin, gemcitabine and pemetrexed, three agents which are currently used to treat MPM in the clinic. OTX015 caused a significant delay in cell growth both in vitro and in vivo. It was the most effective drug in MPM473 xenografts and showed a similar level of activity as the most efficient treatment in the other two MPM models (gemcitabine in MPM487 and cisplatin in MPM484). In vitro studies showed that OTX015 downregulated c‐MYC protein levels in both MPM473 and MPM487 cell lines. Our findings represent the first evidence of promising therapeutic activity of OTX015 in mesothelioma.  相似文献   

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Glioblastomas (GBMs) are high‐grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor‐specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR‐specific affibody (ZEGFR:03115) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near‐infrared light produces a cytotoxic response. ZEGFR:03115–IR700DX EGFR‐specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter‐Glo® assay, and in vivo using subcutaneous U87‐MGvIII xenografts. In addition, mice were imaged pre‐ and post‐PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor‐dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115–IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof‐of‐concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts.  相似文献   

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Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life‐threatening opportunistic infection in HIV‐infected patients. However, non‐HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co‐infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non‐HIV patients. Two cases of pulmonary co‐infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non‐HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non‐Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co‐infection by P. jirovecii and other fungi in non‐HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.  相似文献   

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Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin‐depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store‐bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme‐induced promotion, can suppress promotion by processed meat. A 14‐day study was done to test the effect of nine purchased cured meats on fecal and urinary biomarkers associated with heme‐induced carcinogenesis promotion. Fecal water from rats given hot dog or fermented raw dry sausage was particularly cytotoxic. These two cured meats were thus given to rats pretreated with 1,2‐dimethylhydrazine, to evaluate their effect on colorectal carcinogenesis. After a 100‐days feeding period, fecal apparent total N‐nitroso compounds (ATNC) were assayed and colons were scored for MDF. Hot dog diet increased fecal ATNC and the number of MDF per colon compared with the no‐meat control diet (3.0 ± 1.7 vs. 1.2 ± 1.4, p < 0.05). In a third study, addition of calcium carbonate (150 µmol/g) to the hot dog diet decreased the number of MDF/colon and fecal ATNC compared with the hot dog diet without calcium carbonate (1.2 ± 1.1 vs. 2.3 ± 1.4, respectively, p < 0.05). This is the first experimental evidence that a widely consumed processed meat promotes colon carcinogenesis in rats. It also shows that dietary prevention of this detrimental effect is possible.  相似文献   

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