Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan

Abstract

Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.

http://ift.tt/2uzFbPS

Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life

Abstract

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m²) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04–1.14) and 1.14 (95% CI 1.09–1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.

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Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients

Abstract

Purpose

Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients.

Methods

This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000–2009 from National Health Insurance Program database.

Results

A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61–0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72–0.91) and matched populations (0.86; 0.78–0.95).

Conclusion

This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

http://ift.tt/2wRfZFj

INST OX-05-024: first line gemcitabine, oxaliplatin, and erlotinib for primary hepatocellular carcinoma and bile duct cancers: a multicenter Phase II trial

Abstract

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression-free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.

This is a phase II trial in the first line setting with gemcitabine, oxaliplatin, and erlotinib for primary hepatocellular carcinoma and bile duct cancer. The trial shows interesting results specially in the bile duct cancer arm and this combination should be tested in a randomized setting in comparison with standard of care.

http://ift.tt/2uPd3b7

Mediating burden and stress over time: Caregivers of patients with primary brain tumor

Abstract

There is a growing literature on the effects of cancer caregiving on the well-being of informal family caregivers. However, there has been little longitudinal research on caregivers of patients with the complex, rapidly-changing disease of primary malignant brain tumor (PBT).

Objective

Our objective was to model longitudinal relationships between caregiver burden, social support, and distress within caregivers of patients with PBT.

Methods

Caregiver participants were recruited from a neuro-oncology clinic. Caregiver questionnaire data, including socio-demographics, social support, depression, anxiety, and caregiving burden, were collected at four time points (diagnosis, +4, +8, and +12 months). Using the stress process model as a guide, we hypothesized that early burden would predict later depression and anxiety and this would be mediated by social support.

Results

Using data from 147 participants, we found support for the stress process model in caregivers of patients with PBT. Greater burden at diagnosis was associated with lower social support at 4 months and lower social support was related to higher depression and anxiety at 8 months, as well as to changes in anxiety between 8 and 12 months.

Conclusion

We found evidence of the stress process model in caregivers of PBT patients unfolding over the course of a year after diagnosis. Our findings emphasize the potential importance of early programs for caregivers to ensure low initial levels of burden, which may have a positive effect on social support, depression, and anxiety.

http://ift.tt/2uOZ5pK

In Response.

No abstract available

http://ift.tt/2vNM2Jt

In Response: Concerns With Rate of Rise of Carbon Dioxide During Apnea With Buccal Oxygenation.

No abstract available

http://ift.tt/2vv9NDw