Longer Survival Period Research Articles

Anxiety and depression in women with breast cancer: Social and clinical determinants and influence of the social network and social support (DAMA cohort)

BackgroundAnxiety and depression are the most prevalent mental health pathologies among women with breast cancer. Social, clinical and contextual variables may influence emotional stress among women with breast cancer.The aim of this work is to study anxiety and depression in a cohort of women diagnosed with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and clinical determinants. MethodsWe performed a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were the Hospital Anxiety and Depression questionnaire and hospital medical records. Dependent variables were anxiety and depression; independent variables were social class, age, employment status, tumour stage at diagnosis, time since diagnosis, social network and social support. We performed a descriptive analysis, a bivariate analysis, and a multivariate logistic regression analysis. ResultsA total of 1086 (48.6%) women had some degree of anxiety-related problem. As for depression. In the case of depression, 225 (15%) women had some degree of depression-related problem. Low emotional support and social isolation were clear risk factors for having more anxiety and depression. Low social class was also a risk factor, and age also played a role. DiscussionOur results show that women long period of cancer survival have high prevalences of anxiety than depression, and this prevalence of anxiety is higher than the general population. In addition, we found inequalities between social classes and the isolation and social support are worse too in low social class.

Magnetic resonance imaging evaluation of treatment efficacy and prognosis for brain metastases in lung cancer patients after radiotherapy: A preliminary study.

BackgroundThis study used magnetic resonance imaging (MRI) to monitor changes to brain metastases and investigate the imaging signs used to evaluate treatment efficacy and determine prognosis following radiotherapy for brain metastases from lung cancer.MethodsA total of 60 non‐small cell lung cancer patients with brain oligometastases were selected. MRI scans were conducted before and 3, 6, 9, 12, 18, 24, and 30 months after radiotherapy. The tumor and peritumoral edema diameters, Cho/Cr values, elevation of the Lip peak value, and whether the island (yu‐yuan) sign or high‐signal ring were present on T2 fluid‐attenuated inversion recovery (FLAIR) imaging were recorded for each metastasis.ResultsThe mortality risk was higher the earlier the maximum value of peritumoral edema diameter was reached, when there were fewer island signs, and when brain metastases did not present as tumor progression on imaging. There were significant differences in the average peritumoral edema diameter, apparent diffusion coefficient value, the number of elevated Lip peak values, and the number of T2 FLAIR imaging high‐signal rings in a year after radiotherapy in 14 patients with a survival period < 1 year compared to patients with a survival period > 2 years.ConclusionAfter radiotherapy for brain metastases, patients with the island sign had longer survival periods, high‐signal rings in T2 FLAIR, elevated Lip peaks, and reduced apparent diffusion coefficient values, indicating tumor necrosis. Increased diameter of metastases and Cho/Cr > 2 cannot serve as reliable indicators of brain metastasis progression.

Effect of Resveratrol on Oxidative Stress and Mitochondrial Dysfunction in Immature Brain during Epileptogenesis.

The presence of oxidative stress in immature brain has been demonstrated during the acute phase of status epilepticus (SE). The knowledge regarding the long periods of survival after SE is not unequivocal, lacking direct evidence. To examine the presence and time profile of oxidative stress, its functional effect on mitochondria and the influence of an antioxidant treatment in immature rats during epileptogenesis, status epilepticus (SE) was induced in immature 12-day-old rats by Li-pilocarpine and at selected periods of the epileptogenesis; rat pups were subjected to examinations. Hydroethidine method was employed for detection of superoxide anion (O2.-), 3-nitrotyrosine (3-NT), and 4-hydroxynonenal (4-HNE) for oxidative damage of mitochondrial proteins and complex I activity for mitochondrial function. Natural polyphenolic antioxidant resveratrol was given in two schemes: "acute treatment," i.p. administration 30min before, 30 and 60min after induction of SE and "full treatment" when applications continued once daily for seven consecutive days (25mg/kg each dose). The obtained results clearly document that the period of epileptogenesis studied (up to 4weeks) in immature brain is associated with the significant enhanced production of O2.-, the increased levels of 3-NT and 4-HNE and the persisting deficiency of complex I activity. Application of resveratrol either completely prevented or significantly reduced markers both of oxidative stress and mitochondrial dysfunction. The findings suggest that targeting oxidative stress in combination with current antiepileptic therapies may provide a benefit in the treatment of epilepsy.

143 - Autologous Stem Cell Transplant in Adult Multiple Sclerosis Patients: A Pilot Study From North India

Background: Autologous Stem Cell Transplant (ASCT) has been shown to provide long periods of progression free survival in MS. This is an observational study to demonstrate the safety of ASCT in MS patients at a transplant centre in North India. Objectives: To demonstrate safety and efficacy of ASCT using a lymphoablative regimen in MS patients in North India. Materials and Methods: The study was done in Fortis Memorial Research Institute, Gurgaon, India between January 2017 and September 2017. Patient selection- MS patients who were either referred by a neurologist or who came of their own volition were evaluated for feasibility. Kurtzke Expanded Disability Status Scale (EDSS) score was calculated for all patients and those with a score of >7 were excluded. Patients <18 years were excluded. Informed written consent was taken from all patients. Conditioning regimen- Mobilization was done with G-CSF (10 mcg/kg/day) with prednisolone (1 mg/kg/day) to prevent disease flare-up. A minimum of 2 x 106 CD34 cells/kg were collected. Conditioning regimen consisted of Rabbit ATG .5 mg/kg on day -6 followed by 1 mg/kg on day -5 to -2 and Cyclophosphamide 50 mg/kg on day-5 to -2. In addition, Rituximab 375 mg/m2 was given on day-7 and day+30 to prevent EBV reactivation and disease relapse. Antibiotic prophylaxis was given with levofloxacin, fluconazole and valacyclovir. Any persistent change in the EDSS score ≥1 was considered significant. Results: A total of 12 patients were included in this study. The patient demographics and clinical details are mentioned in Table 1.Table 1Demographic and Clinical Data of Ms Patients Who Underwent ASCTSr. noAgeGenderDiagnosisActive lesion in MRI brainActive lesion in MRI spineCD34 Cell dose (106/kg)Day of neutrophil engraftmentEDSS at diagnosisEDSS at last follow upFollow up post-transplant (in days)128MSPMSNoNo2.71+96.56.5124232FSPMSNoNo13.19+106.56.5118322FRRMSNoNo6.15+93.53.5123465MSPMSNoNo7.08+1066148539MRRMSYesNo6+96678631FSPMSNoNo6.87+105.55.5177744FSPMSNoNo5.3+86.56.5250837FSPMSNoNo6+85.55.5103949FSPMSNoNo2.69+75.55.5781028FSPMSNoNo11.15+8771241129FRRMSYesNo3.86+855431231FRRMSYesYes8.71+92130Median→31.56.0795.755.75120.5Range22-652.69-13.197-102-71-730-250M indicates Male; F, Female. Open table in a new tab M indicates Male; F, Female. Five patients (No. 3, 4, 7, 10, 12) had positive urine cultures prior to transplant and were treated before starting any chemotherapy. Majority of the patients were women (9/12). All patients developed febrile neutropenia which was managed as per department policy. There was no mortality. Subjective symptoms improved in 11/12 patients. EDSS score improved in 1 patient with RRMS. Conclusion: The dataset is very small and the follow up is short to draw any conclusions regarding outcome. Like other studies which have been done, our data shows that patients with SPMS do not show significant improvement, at least in the short term.

Sleep Pattern and Predictors of Sleep Disturbance Among Family Caregivers of Terminal Ill Patients With Cancer in Taiwan: A Longitudinal Study.

Sleep disturbance commonly has a negative impact on the well-being of family caregivers (FCs) of terminally ill patients with cancer. The effect of sleep disturbance on FCs has not been explored through long-term follow-up studies in Taiwan. The purposes of this study were to (1) identify the trajectory of sleep quality of FCs of terminally ill patients with cancer in Taiwan and (2) examine the determinants of sleep disturbance through a longitudinal follow-up until patient death. A prospective, longitudinal study was conducted among 95 FCs of terminally ill patients with cancer. The FCs' sleep quality was measured subjectively by using the Pittsburgh Sleep Quality Index and objectively by wearing a wrist actigraphy for 48 hours each month during the 6-month follow-up assessments. The trajectory and determinants of sleep quality were identified using a generalized estimation equation approach. The FCs' sleep quality significantly decreased as the patient's death approached. Family caregivers who were women or older, had a relative with a longer survival period after diagnosis, reported higher levels of depression and fatigue, and provided lower levels of assistance to their relatives experienced more sleep disturbance. The sleep quality of Taiwanese FCs significantly deteriorated as the death of the terminally ill patients with cancer approached. Early detection of the FCs' sleep disturbance, increasing their self-awareness of sleep problems, and providing nonpharmacological interventions and psychosocial support may be helpful for FCs to improve their quantity and quality of sleep.

MicroRNA-329 inhibits cell proliferation and tumor growth while facilitates apoptosis via negative regulation of KDM1A in gastric cancer.

Altered expression of microRNA (miRNA) is strongly implicated in gastric cancer (GC). Here, we demonstrated a decreased expression of miRNA-329 in GC. Then we explored the regulatory mechanisms responsible for its effect on GC cells. GC tissues and their adjacent non-tumor tissues were collected. Complete follow-up was updated. A series of inhibitors, mimics, and siRNA against KDM1A were introduced to validate regulatory mechanisms for miR-497 and KDM1A in BGC-823 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were employed for evaluating the expressions of miRNA-329, KDM1A, H3K4me1, and H3K4me2. Cell proliferation, cycle progression, and apoptosis were assessed by means of an MTT assay and flow cytometry. Cell colony formation was assessed. uman gastric cancer xenotransplanted into nude mice was studied. As opposed to adjacent tissues and gastritis tissues, miRNA-329 was highly expressed and KDM1A was low expressed in GC tissues. The patients with high miRNA-329 expression or low KDM1A expression had longer survival periods. The miRNA-329 mimics and siRNA against KDM1A decreased KDM1A expression and increased H3K4me1 and H3K4me2 expressions. Forced expression of miRNA-329 in gastric cancer cells significantly promotes their capacity of apoptosis but reduces proliferation, migration, and invasion. KDM1A is a direct downstream target for miRNA-329. In a nude mouse subcutaneous tumor system, in vivo tumor growth of BGC-823 was significantly inhibited after treatment of miRNA-329 mimics or siRNA against KDM1A. We conclude that miRNA-329 functions as a tumor suppressor in GC, which could be achieved via transcriptional suppression of KDM1A.

Clinical significance and practice points of conversion therapy for gastric cancer with peritoneal metastasis

Gastric cancer with peritoneal dissemination is usually considered to be oncologically unresectable and is known to have a very poor prognosis. Despite recent advances in systemic chemotherapy, peritoneal dissemination due to advanced gastric cancer (AGC) still remains the most life-threatening type of metastasis and recurrence, which usually causes ascites accumulation, intestinal obstruction, or hydronephrosis, and then seriously impairs the quality of life. In general, the median survival time of these cases is reported to be just only 6-9 months. Recently, conversion therapy for gastric cancer with peritoneal dissemination has been highly concerned. It is defined as a conversion surgery aiming at an R0 resection after chemotherapy for both primary gastric cancer and distant metastatic cancerous foci including peritoneal dissemination, which were originally unresectable due to technical and/or oncological reasons. In numerous clinical practices, the results of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) have been reported to be more satisfactory in comparison with traditional systemic chemotherapy alone. Some clinical trials have demonstrated the clinical efficacy of intravenous and intraperitoneal administration of paclitaxel (PTX) combined with oral S-1 for peritoneal dissemination of gastric cancer with or without malignant ascites. Particularly, a longer period of survival can be expected when conversion R0 gastrectomy is successfully performed after observing significant responses of NIPS. Some clinical practice key points of conversion therapy for AGC patients with peritoneal dissemination are reviewed, including the importance of intraperitoneal and systemic synchronous chemotherapy, the reasonable choice of intraperitoneal chemotherapy drugs, the evaluation of primary gastric cancer and metastatic foci before and after conversion therapy, some special complications of NIPS, the indications of conversion surgery and the adjuvant therapy after conversion surgery, ect.

Apoferritin Nanocage for Brain Targeted Doxorubicin Delivery.

An ideal brain-targeted nanocarrier must be sufficiently potent to penetrate the blood-brain barrier (BBB) and sufficiently competent to target the cells of interest with adequate optimized physiochemical features and biocompatibility. However, it is an enormous challenge to the researchers to organize the above-mentioned properties into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. Herein, we demonstrate a straightforward strategy for brain targeting by encapsulating doxorubicin (DOX) into a naturally available and unmodified apoferritin nanocage (DOX-loaded APO). APO can specifically bind to cells expressing transferrin receptor 1 (TfR1). Because of the high expression of TfR1 in both brain endothelial and glioma cells, DOX-loaded APO can cross the BBB and deliver drugs to the glioma with TfR1. Subsequent research demonstrated that the DOX-loaded APO had good physicochemical properties (particle size of 12.03 ± 0.42 nm, drug encapsulation efficiency of 81.8 ± 1.1%) and significant penetrating and targeting effects in the coculture model of bEnd.3 and C6 cells in vitro. In vivo imaging revealed that DOX-loaded APO accumulated specifically in brain tumor tissues. Additionally, in vivo tumor therapy experiments (at a dosage of 1 mg/kg DOX) demonstrated that a longer survival period was observed in mice that had been treated with DOX-loaded APO (30 days) compared with mice receiving free DOX solution (19 days).

Effects of single and combined use of bacteriophages and antibiotics to inactivate Escherichia coli

A major concern of phage therapy is the emergency of phage-resistant mutants. This limitation can be overcome by the combined use of phages and antibiotics. It has been shown that the combination of antibiotics and phages is an alternative that cannot only be effective at reducing bacterial numbers, but also to contribute to the management of resistance levels. However, this view has only been discussed with regard to antibiotic resistance and not to control phage-mutant emergence. In our study we compared not only the resistance of the bacteria to the four antibiotics tested with and without phages addition, but also the resistance to the phages in the presence and absence of antibiotics. The aim of this study was to evaluate the potential synergistic effect of phages and antibiotics in the inactivation of Escherichia coli in order to control infections, namely urinary tract infection (UTI), and to reduce the development of bacterial resistance to phages. Phage therapy combined with antibiotics (ampicillin, piperacillin, kanamycin, tetracycline, chloramphenicol and ciprofloxacin) was evaluated in the inactivation of E. coli, both in saline solution and urine samples. Phage and antibiotic combinations could result in high synergistic effects in the inactivation of bacteria. The combination of phage and ciprofloxacin at sublethal concentration decreased the bacterial counts in urine samples by 7.8±0.1 log CFU/ml after 8h, but when phages or the antibiotic were tested alone, the decrease was of 3.9±0.3 log CFU/mL and 1.2±0.1 log CFU/mL, respectively, after the same time. The efficacy of the combination of the two therapies depends on the antibiotic resistance status of the targeted bacteria to the employed antibiotic and of the antibiotic type (bactericide or bacteriostatic), causing the same or less bacterial resistance than phages and antibiotics applied alone (1.2±1.0×10−5 to 2.4±1.5×10−7 CFU/mL for the combined treatment, 2.7±0.2×10−4 CFU/mL for the antibiotics and 5.0±1.5×10−6 CFU/mL for the phages). The addition of antibiotics, at subinhibitory concentration, during phage treatment can control the phage-mutant. The high bacterial inactivation efficiency of these combined techniques and the long periods of phage survival in urine, pave the way for depth studies to control UTI and to overcome the development of resistances by bacteria.

Care needs of cancer patients undergoing ambulatory treatment

El cáncer provoca cambios físicos, emocionales y sociales que generan diversas necesidades en los pacientes y sus familias. La menor estancia hospitalaria, la mayor sobrevida y el amplio número de pacientes que se mantienen en sus hogares recibiendo cuidado, han creado una mayor necesidad de asistencia en aspectos como el transporte de los pacientes, el cuidado en casa, el desarrollo de las actividades de la vida diaria y en la forma de reducir los costos que la enfermedad genera. Se realizó un estudio transversal que exploró las necesidades de atención de salud de 173 pacientes con cáncer sometidos a tratamiento ambulatorio en tres unidades de oncología especializados en dos hospitales de Bogotá, mediante el uso de la Encuesta de Necesidades (SCNS-SFS28) validada en castellano en población colombiana. Casi la mitad de los pacientes (46,95%) informó necesidades de cuidado en al menos uno de los cinco dominios considerados. La identificación de las necesidades de cuidado es especialmente importante en el caso de los pacientes con alto riesgo de tenerlas desatendidas porque éstas pueden afectar negativamente la adherencia al tratamiento, el estado de salud y calidad de vida. Un cuestionario como el que fue empleado en este estudio permite a las enfermeras identificar las necesidades de cuidado adecuados de los pacientes. Los cuidados de enfermería deben tener en cuenta las necesidades particulares de todos los pacientes con el fin de enseñarles a ellos y a sus familias como para proporcionar el autocuidado eficaz, para resolver los problemas de salud y para satisfacer las necesidades de cuidado del paciente.

Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles

Treatment of brain tumor remains a great challenge worldwide. Development of a stable, safe, and effective siRNA delivery system which is able to cross the impermeable blood-brain barrier (BBB) and target glioma cells is necessary. This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system. In vitro cellular uptake experiments demonstrated a higher intracellular fluorescence intensity of siRNA in brain microvascular endothelial cells (BMVECs) and U87 glioma cells when treated with T7-LPC/siRNA NPs compared with PEG-LPC/siRNA NPs. In the co-culture model of BMVECs and U87 cells, a significant down-regulation of EGFR protein expression occurred in the U87 glioma cells after treatment with the T7-LPC/siEGFR NPs. Moreover, the T7-LPC/siRNA NPs had an advantage in penetrating into a deep region of the tumor spheroid compared with PEG-LPC/siRNA NPs. In vivo imaging revealed that T7-LPC/siRNA NPs accumulated more specifically in brain tumor tissues than the non-targeted NPs. Also, in vivo tumor therapy experiments demonstrated that the longest survival period along with the greatest downregulation of EGFR expression in tumor tissues was observed in mice with an intracranial U87 glioma treated with T7-LPC/siEGFR NPs compared with mice receiving other formulations. Therefore, we believe that these transferrin receptor-mediated core-shell nanoparticles are an important potential siRNA delivery system for brain tumor-targeted therapy.

Status Epilepticus in Immature Rats Is Associated with Oxidative Stress and Mitochondrial Dysfunction.

Epilepsy is a neurologic disorder, particularly frequent in infants and children where it can lead to serious consequences later in life. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of many neurological disorders including epilepsy in adults. However, their role in immature epileptic brain is unclear since there have been two contrary opinions: oxidative stress is age-dependent and does not occur in immature brain during status epilepticus (SE) and, on the other hand, evidence of oxidative stress in immature brain during a specific model of SE. To solve this dilemma, we have decided to investigate oxidative stress following SE induced in immature 12-day-old rats by three substances with a different mechanism of action, namely 4-aminopyridine, LiCl-pilocarpine or kainic acid. Fluoro-Jade-B staining revealed mild brain damage especially in hippocampus and thalamus in each of the tested models. Decrease of glucose and glycogen with parallel rises of lactate clearly indicate high rate of glycolysis, which was apparently not sufficient in 4-AP and Li-Pilo status, as evident from the decreases of PCr levels. Hydroethidium method revealed significantly higher levels of superoxide anion (by ∼60%) in the hippocampus, cerebral cortex and thalamus of immature rats during status. SE lead to mitochondrial dysfunction with a specific pronounced decrease of complex I activity that persisted for a long period of survival. Complexes II and IV activities remained in the control range. Antioxidant treatment with SOD mimetic MnTMPYP or peroxynitrite scavenger FeTPPS significantly attenuated oxidative stress and inhibition of complex I activity. These findings bring evidence that oxidative stress and mitochondrial dysfunction are age and model independent, and may thus be considered a general phenomenon. They can have a clinical relevance for a novel approach to the treatment of epilepsy, allowing to target the mechanisms which play a crucial or additive role in the pathogenesis of epilepsies in infants and children.

Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer

Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years (average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination.

Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management.

Answer questions and earn CME/CNE Cancer and heart disease are the leading causes of morbidity and mortality in the industrialized world. Modern treatment strategies have led to an improvement in the chances of surviving a diagnosis of cancer; however, these gains can come at a cost. Patients may experience adverse cardiovascular events related to their cancer treatment or as a result of an exacerbation of underlying cardiovascular disease. With longer periods of survival, late effects of cancer treatment may become clinically evident years or decades after completion of therapy. Current cancer therapy incorporates multiple agents whose deleterious cardiac effects may be additive or synergistic. Cardiac dysfunction may result from agents that can result in myocyte destruction, such as with anthracycline use, or from agents that appear to transiently affect left ventricular contractility. In addition, cancer treatment may be associated with other cardiac events, such as severe treatment-induced hypertension and vasospastic and thromboembolic ischemia, as well as rhythm disturbances, including QTc prolongation, that may be rarely life-threatening. Early and late effects of chest radiation can lead to radiation-induced heart disease, including pericardial disease, myocardial fibrosis, cardiomyopathy, coronary artery disease, valvular disease, and arrhythmias, in the setting of myocardial fibrosis. The discipline of cardio-oncology has developed in response to the combined decision making necessary to optimize the care of cancer patients, whether they are receiving active treatment or are long-term survivors. Strategies to prevent or mitigate cardiovascular damage from cancer treatment are needed to provide the best cancer care. This review will focus on the common cardiovascular issues that may arise during or after cancer therapy, the detection and monitoring of cardiovascular injury, and the best management principles to protect against or minimize cardiotoxicity during the spectrum of cancer treatment strategies. CA Cancer J Clin 2016;66:309-325. © 2016 American Cancer Society.

Klotho: a tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinoma

Klotho, an anti-aging gene, has recently been shown to contribute to human hepatic tumorigenesis. In addition, it is known that Wnt signaling is antagonized by the protein klotho. Because augmented Wnt signaling has an important role in tumorigenesis of human hepatocellular carcinoma (HCC), we studied the relationship of klotho expression and activity to the Wnt pathway in this malignancy. Immunohistochemical analysis performed on tissue arrays revealed that klotho expression levels were significantly lower in HCC than in adjacent noncancerous tissues, while klotho staining was inversely correlated with clinical stage and histologic grade. Patients with klotho-expressing tumors had longer survival periods than did those with klotho-negative tumors. Overexpression of klotho as well as treatment with soluble klotho protein reduced hepatoma cell growth in vitro and in vivo, whereas klotho silencing enhanced cellular proliferation. Moreover, forced expression of klotho inhibited Wnt/β-catenin signaling, as confirmed by reduced expression of β-catenin, inhibition of translocation of β-catenin from the cytoplasm to the nucleus, and reduced expression of c-myc and cyclin D1, two known target genes of the Wnt/β-catenin pathway. In contrast, activation of the Wnt/β-catenin pathway was enhanced when klotho was silenced by inhibitory RNAs. Furthermore, serum levels of soluble klotho in patients with malignant tumors were studied, and results suggested a significant increase in these levels in HCC patients. These data suggest that klotho acts as a tumor suppressor and an inhibitor of the Wnt/β-catenin pathway in HCC, and moreover, that soluble klotho is a potential serum biomarker for HCC.

Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer.

This study was designed to discuss feasibility, short-term efficacy, and complications of iodine-125 radioactive seed tissue implantation for remedying recurrent cervical cancer. From June 2009 to December 2010, 17 patients with recurrent cervical cancer received radioactive seed implantation under computed tomography (CT) guidance. Matched peripheral dose was 145 Gy, while the number of implanted seeds was from 6 to 68 with a median of 20. Efficacy was determined based on the results of CT and 18 F-fluorodeoxyglucose positron emission tomography/CT. Postoperative follow-ups were from 4 to 18 months with a median follow-up time of 9.5 months. Nine patients died during follow-up while remaining patients survived during the follow-up period. Evaluation of efficacy: six patients had a complete response, four patients had a partial response, and seven patients had progressive disease, clinical efficacy rate as 58% (10/17). No patients had complications of radiation injury. Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively. Comparing to patients who responded ineffectively to radioactive seed implantation, patients who responded effectively to radioactive seed implantation had a longer survival period (median 7.2 vs. median 10.4), in which the difference was statistically significant (P = 0.038). Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe treatment method for remedying or palliative treatment of recurrent cervical cancer. Patients who have recurrent cervical cancer and responded effectively to radioactive seed implantation will have a longer survival period.

Prosthetic Rehabilitation After Hip Disarticulation or Hemipelvectomy.

Prosthetic rehabilitation after pelvic-level amputation (hemipelvectomy/hip disarticulation) is difficult, and because of this, many patients are never fit with a prosthetic limb. The objectives of the study were to evaluate the characteristics of successful prosthetic users and to determine what factors are associated with successful prosthetic fitting and use. The authors identified 43 patients who underwent hip disarticulation/hemipelvectomy between 2000 and 2010 and were candidates for prosthetic fitting at the authors' institution. The medical records of these patients were then reviewed for pertinent demographic and medical characteristics to identify the profile of successful prosthetic users. Of 43 patients, 18 (43%) successfully used a prosthetic limb. The only preoperative factor associated with unsuccessful prosthetic fitting was coronary artery disease. Specifically, age, body mass index, other medical comorbidities, and demographic characteristics were not associated with successful or unsuccessful prosthetic fitting. Successful users wore their prosthesis an average of 5.8 hrs/day, and most ambulated with one or both hands free. Successful prosthetic rehabilitation after hemipelvectomy and hip disarticulation is possible. Increased body mass index, advanced age, depression, and other comorbidities should not discourage prosthetic rehabilitation. Most patients that undergo prosthetic rehabilitation enjoy long periods of survival and wear their prosthesis for most of the day.

Salvage photodynamic therapy for local failure after chemoradiotherapy for esophageal squamous cell carcinoma

Photodynamic therapy (PDT) is a less-invasive salvage treatment option for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma. The objective of this study was to clarify the long-term outcomes and prognostic factors of salvage PDT. One hundred thirteen consecutive patients treated in our institution with PDT for local failure limited to within T2 without any metastases after definitive CRT performed between 1998 and 2008 were retrospectively enrolled. The complete response rate, adverse events, and survival outcomes were assessed and prognostic factors were investigated using a multivariate analysis. The complete response rate was 58.4% (95% confidence interval [CI], 49.3%-67.5%). The progression-free survival (PFS) and the overall survival (OS) rates at 5 years after salvage PDT were 22.1% (95% CI, 14.3%-30.0%) and 35.9% (95% CI, 26.7%-45.1%). N0 before CRT was significantly associated with OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91, P= .020), whereas the impact of T1 or T2 before CRT on PFS (HR, 0.63; 95% CI, 0.38-1.04, P= .068) and that of a longer period between CRT and PDT on OS (HR, 0.64; 95% CI, 0.39-1.05, P= .078) were marginal. The treatment-related death rate was 1.8%. Salvage PDT was found to have a superior outcome and a satisfactory safety profile. An earlier clinical stage before CRT and a longer interval between CRT and PDT may be associated with a longer survival period.

Potential of phage cocktails in the inactivation of Enterobacter cloacae—An in vitro study in a buffer solution and in urine samples

The objective of this study was to compare the dynamics of three previously isolated phages for Enterobacter cloacae in order to evaluate their ability to treat urinary tract infections (UTI). The phages genomes, survival, host range, were characterized, and the host-phage dynamics was determined in culture medium and urine samples. The presence of prophages in bacteria, host recovery and development of resistance to phage after treatment was also evaluated. The growth of the E. cloacae was inhibited by the three phages, resulting in a decrease of ≈3log. The use of cocktails with two or three phages was significantly more effective (decrease of ≈4log). In urine, the inactivation was still effective (≈2log). Both phages were considered safe to inactivate the bacteria (no integrase and toxin codifying genes). Some bacteria remained viable in the presence of the phages, but their colonies were smaller than those of the non-treated control and were visible only after 5 days of incubation (visible after 24h in the control). A high bacterial inactivation efficiency with phage cocktails combined with the safety of the phages and their long periods of survival, even in urine samples, paves the way for depth studies, especially in vivo studies, to control urinary tract infection and to overcome the development of resistances by the nosocomial bacterium E. cloacae.

The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors.

Low-frequency ultrasound (US) in combination with microbubbles (MBs) is able to inhibit the growth of VX2 rabbit liver tumors. In this study, we investigated the feasibility of using percutaneous ethanol injection (PEI) followed by low-frequency ultrasound and microbubbles (USMB) to inhibit VX2 tumor growth. Eighteen New Zealand rabbits with hepatic VX2 tumors were divided into three groups: PEI, low-frequency ultrasound and MBs followed by PEI (USMB + PEI), and PEI followed by USMB (PEI + USMB). PEI was performed by ultrasound-guided injection of 95% anhydrous alcohol into internal liver tumors in rabbits twice a week for 2 weeks. The US parameters were 20 kHz, 2 W/cm(2), 40% duty cycle, 5 min, and once every other day for 2 weeks. Magnetic resonance imaging (MRI) was used to observe tumors before and after treatment, to examine changes in the tumors, and to measure the diameters of the tumors. All animals were followed up for 180 days after tumor implantation. Autopsy was performed at the end of the scheduled follow-up or immediately after death. Anatomically observed metastatic sites included the liver, lung, abdomen, and pelvic cavity. The survival time of all rabbits was recorded. After 4 weeks of treatment, on MRI, the tumor diameters in the PEI, USMB + PEI, and PEI + USMB groups were 8.33 ± 1.83, 19 ± 2.61, and 4.5 ± 1.22 mm, respectively. There was a significant difference in tumor size indicated by MRI in the three groups. Tumor size was smaller in the PEI + USMB group than in the PEI and USMB + PEI groups, with t = 4.54, p = 0.0062, and t = 16.38, p < .0001, respectively. The PEI + USMB group showed the fewest metastasis sites (χ(2) = 11.7333, p = 0.0194) and the longest survival period (χ(2) = 7.448, p = 0.0241). Percutaneous ethanol injection followed by low-frequency ultrasound and microbubbles can be effective in inhibiting rabbit liver tumors and prolonging survival time.