Promising therapeutics of gastrointestinal cancers in clinical trials

Many novel therapeutics are being developed for patients with cancers along the gastrointestinal (GI) tract. These emerging agents are frequently classified by their biological targets such as tumor growth pathways, tumor metabolism, microenvironment, etc. Some agents targeting cancer growth pathways are based on existing clinically validated therapeutic targets, such as regorafenib for hepatocellular carcinoma (HCC), while other agents focus on newly identified targets, such a

Lung cancer treatment outcomes in recipients of lung transplant

BACKGROUND: Lung transplant recipients develop lung cancer more commonly than the general population. The best treatment approach for these patients is unclear. The goal of this study is to evaluate treatment outcomes in this population. METHODS: We used the Cleveland Clinic lung transplant database to identify patients diagnosed with lung cancer at the time of or after lung transplant. Transplant and lung cancer-related data were retrospectively reviewed. RESULTS: Among 847 patients underwent lung transplant between 2005 and 2013, 17 (2%) were diagnosed with lung cancer and included. Median age was 61 (range, 48–70) years. Majority were stage I/II (n=11), one had stage IIIA, five had stage IV. Non-small cell lung cancer (NSCLC) were more common than small cell lung cancer (SCLC) (n=15 vs. 2). Curative treatment was performed as lobectomy in native lung (n=1), and radiation in transplanted lung (n=2). Chemotherapy was given in 10 patients, primarily carboplatin-based doublets with docetaxel, pemetrexed, or etoposide. Six of these received palliative chemotherapy for either metastases at diagnosis (n=3) or recurrence after early stage disease (n=3). Except for one patient with complete response, all others had progressive disease following palliative chemotherapy. Overall, patients who received chemotherapy had a median survival of 7.5 months from the initiation of chemotherapy, but 30% developed grade 5 sepsis. Median survival for stage I–IIIA and stage IV were 23.2 and 2.5 months respectively. CONCLUSIONS: Lung cancer in lung transplant recipients carries various clinical courses. Patients with metastatic disease have substantial toxicities from chemotherapy and poor survival. Early stage patients should be offered treatment with modified dosages to decrease the risk of severe toxicities

Expression of androgen and estrogen receptors in the testicular tissue of chickens, quails and chicken-quail hybrids

36 New Roman cocks, 30 Korean male quails and 30 chicken-quail hybrids of different day-age were selected and their body weight and testes weights were measured and as well, their testes were collected. Real-time polymerase chain reaction (RT-PCR) was performed to evaluate the messenger ribonucleic acid (mRNA) expression patterns of androgen receptors (AR) and estrogen receptors (ER) genes in testicular tissue of chickens, quails and chicken-quail hybrids at different growth stages. The results show that the testes of chickens and quails grew and developed normally with body weight gain, but the testes of chicken-quail hybrids had a slower growth rate and stunted growth. Real-time PCR showed AR and ER mRNA expression patterns in testes of chickens and quails at different growth stages were similar. AR mRNA expression in chickens and quails reached a significant peak at 80 and 30 days of age, respectively and their ER gene expression showed fluctuation slightly. The AR and ER expression of chicken-quail hybrids were different from the above expression patterns; the hybrids AR gene expression showed a gradual decline and ER gene expression gradually increased. The chickenquail hybrids AR and ER gene expression was abnormal and we speculate this is an important molecular factor for the testicular dysplasia of chicken-quail hybrids. Our results show that AR gene expression was upregulated by ER gene and we suggest that the synergetic effect of AR and ER gene regulated the normal testis growth and development of chicken and quail.Keywords: Chicken, quail, chicken-quail hybrid, testis, androgen receptors (AR), estrogen receptors (ER) expressionAfrican Journal of Biotechnology Vol. 11(29), pp. 7344-7353, 10 April, 201

Hypoxia-Inducible Factor 1-Alpha Reduces Infarction and Attenuates Progression of Cardiac Dysfunction After Myocardial Infarction in the Mouse

ObjectivesThe aim of this research was to test whether constitutive expression of hypoxia-inducible factor 1-alpha (HIF-1α) influences infarction size and cardiac performance after myocardial infarction.BackgroundA major question in clinical medicine is whether infarction size and border zone remodeling of the heart can be influenced by the overexpression of specific genes in the peri-infarction region.MethodsWe investigated the role of constitutive HIF-1α expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the HIF-1α gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in HIF-1α transgenic mice and control animals. Extent of infarction was then quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathologic analysis of heart samples in infarct, peri-infarct, and remote heart regions at serial time points.ResultsConstitutive overexpression of HIF-1α in the murine heart resulted in attenuated infarct size and improved cardiac function 4 weeks after myocardial infarction. Significantly, we found an increase in both capillary density as well as vascular endothelial growth factor and inducible nitric oxide synthase expression in peri-infarct and infarct regions in the hearts of constitutive HIF-1α–expressing animals compared to control animals.ConclusionsThese observations suggest the involvement of HIF-1α in myocardial remodeling and peri-infarct vascularization. Our results show that supranormal amounts of this peptide protect against extension of infarction and improve border zone survival in myocardial infarction

Clinical Study of Toutongning Capsule Combined with Instant Cardio-reliever Pills and Metoprolol in the Treatment of Migraine

Objective: To observe the clinical effect of Toutongning capsule combined with Instant Cardio-reliever pills, metoprolol in the treatment of migraine. Method: 150 cases of migraine were randomly divided into 3 groups, 50 cases in the treatment group. Using the headache Ning capsule combined with Instant Cardio-reliever pills, metoprolol treatment. The control group A50 cases, metoprolol combined with flunarizine hydrochloride treatment. The control group B50 cases, the application of the town of brain Ning capsule combined with quick acting to save the heart pill treatment, observation and comparison of 3 groups of migraine patients after treatment efficacy and symptom classification comparison. Results: After treatment in January, the effect of migraine in treatment group was significantly higher than that of the two control group (p < 0.05), and the symptom grade of treatment group was significantly improved compared with that of control group (p < 0.01). Conclusion: Headache Ning capsule combined with Instant Cardio-reliever pills, metoprolol in the treatment of migraine has significant curative effect, effective control of headache and to improve the quality of life in patients with migraine, and the safety is high, not prone to side effects, provides a new way to cure the ills of migraine

Long-term outcomes of nasopharyngeal carcinoma treated with helical tomotherapy using simultaneous integrated boost technique: A 10-year result

BackgroundTo evaluate the long-term survival and treatment-related toxicities of helical tomotherapy (HT) in nasopharyngeal carcinoma (NPC) patients.MethodsOne hundred and ninety newly diagnosed non-metastatic NPC patients treated with HT from September 2007 to August 2012 were analyzed retrospectively. The dose at D95 prescribed was 70-74Gy, 60-62.7Gy and 52-56Gy delivered in 33 fractions to the primary gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), respectively, using simultaneous integrated boost technique. The statistical analyses were performed and late toxicities were evaluated and scored according to the Common Terminology Criteria for Adverse Events (version 3.0).ResultsThe median follow-up time was 145 months. The 10-year local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 94%, 95%, 86%, and 77.8%; respectively. Fifty (26.3%) patients had treatment-related failures at the last follow-up visit. Distant metastasis, occurred in 25 patients, was the major failure pattern. Multivariate analysis showed that age and T stage were independent predictors of DMFS and OS, Concomitant chemotherapy improved overall survival, but anti-EGFR monoclonal antibody therapy failed. The most common late toxicities were mainly graded as 1 or 2.ConclusionsHelical tomotherapy with simultaneous integrated boost technique offered excellent long-term outcomes for NPC patients, with mild late treatment-related toxicities. Age and clinical stage were independent predictors of DMFS and OS. And, concurrent chemotherapy means better OS. Further prospective study is needed to confirm the superiority of this technology and to evaluate the roles of anti-EGFR monoclonal antibody treatment

Study of Histopathological and Molecular Changes of Rat Kidney under Simulated Weightlessness and Resistance Training Protective Effect

To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration

Phase Ib/II study combining tosedostat with capecitabine in patients with advanced pancreatic adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. We evaluated the safety and efficacy of the aminopeptidase inhibitor tosedostat with capecitabine in advanced PDAC. Methods: We conducted a phase Ib/II trial of tosedostat with capecitabine as second-line therapy for advanced PDAC. Planned enrollment was 36 patients. Eligible patients were treated with capecitabine 1,000 mg/m Results: Sixteen patients were enrolled. Tosedostat 120 mg oral twice daily with capecitabine 1,000 mg/m Conclusions: Tosedostat with capecitabine displayed tolerable toxicity, and prolonged disease control in a subset of patients. These data encourage further exploration of aminopeptidase inhibitors in pancreatic cancer