Human Papillomavirus (HPV) Vaccination Motivators, Barriers, and Brochure Preferences Among Parents in Multicultural Hawai‘i: a Qualitative Study

Abstract

The human papillomavirus (HPV) vaccine can prevent cervical and other cancers. Unfortunately, according to the National Immunization Survey—Teen 2014 data, completion of the HPV vaccine was only 38 % for 13- to 17-year-old girls and 31 % for 13- to17-year-old boys in the USA, and prevalence was similar in Hawai'i. Parents' acceptability of the HPV vaccine is critical for the vaccine uptake, and this can be increased by educational materials and interventions. However, HPV materials are not widely distributed in Hawai'i. The purpose of this qualitative study was to identify HPV vaccination barriers, motivators, and brochure preferences among parents of teens in multicultural Hawai'i. Twenty parents were interviewed in person or by telephone. Four major themes emerged: (1) the physician is critical in the decision to vaccinate, (2) parental perception of the child's sexual activity guides the timing of their willingness to vaccinate, (3) HPV health education materials should be provided and discussed by the physician, and (4) parents would prefer an educational brochure that features local faces and testimonials, includes an immunization chart, and addresses barriers to vaccination. These findings informed the development of HPV health education materials tailored to Asian Americans and Pacific Islanders in Hawai'i.

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Evolving Strategies for the Treatment of Chronic Lymphocytic Leukemia in the Upfront Setting

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of marked clinical heterogeneity, and while some patients have a normal life expectancy, others develop rapidly progressive disease shortly after diagnosis. The current standard for upfront treatment of CLL is chemoimmunotherapy for younger fit patients, FCR (fludarabine, cyclophosphamide, and rituximab) being the prototype. For older patients, BR (bendamustine and rituximab) exhibits excellent activity with decreased toxicity. For the frailest patients, CD20 monoclonal antibodies with or without chlorambucil have proven to be efficacious. The novel oral kinase inhibitors ibrutinib and idelalisib are FDA-approved in the relapsed/refractory setting, and ibrutinib is approved upfront for those with del(17p). These drugs have produced long-term durable responses in the relapsed/refractory setting, and studies are underway using these as single agent upfront or in combination with both chemotherapy and monoclonal antibodies. Here, we review standard upfront therapies and new agents and combinations that are on the horizon for CLL.

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Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries

Abstract

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140–178 days irrespective of the number of SRS(s) (interquartile range 60–300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

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Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215-MG cells, which correlated with MGMT promoter methylation status. Treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation. Treatment with TMZ specifically reduced the expression of NRP-1, a coreceptor of VEGF but not those of VEGF-R1 and VEGF-R2. We further confirmed the key role of NRP-1 by showing that the reduction of NRP-1 by siRNA also increased the SU1498-induced cytotoxicity of LN215-MG. These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.

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Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries

Abstract

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140–178 days irrespective of the number of SRS(s) (interquartile range 60–300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

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Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215-MG cells, which correlated with MGMT promoter methylation status. Treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation. Treatment with TMZ specifically reduced the expression of NRP-1, a coreceptor of VEGF but not those of VEGF-R1 and VEGF-R2. We further confirmed the key role of NRP-1 by showing that the reduction of NRP-1 by siRNA also increased the SU1498-induced cytotoxicity of LN215-MG. These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.

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The conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.

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