Enhancing preventive medicine over curative medicine: Role of telemedicine.

Historically, healthcare has been skewed towards curative medicine neglecting preventive care leading to high cases of preventable diseases and mortalities. Preventive medicine does not only contribute towards improving health and well-being (SDG3) but also reduces poverty (SDG1). This article aims to highlight the need for prioritizing preventive medicine over curative medicine and also explore opportunities of telemedicine in its promotion.

Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance.

Recurrence of therapy-resistant tumors is a principal problem in solid tumor oncology, particularly in ovarian cancer. Despite common complete responses to first line, platinum-based therapies, most women with ovarian cancer recur, and eventually, nearly all with recurrent disease develop platinum resistance. Likewise, both intrinsic and acquired resistance contribute to the dismal prognosis of pancreatic cancer.

CLPTM1L/CRR9 ectodomain interaction with GRP78 at the cell surface signals for survival and chemoresistance upon ER stress in pancreatic adenocarcinoma cells.

Altered regulation of endoplasmic reticulum (ER) homeostasis has been implicated in many cancers and has recently become a therapeutic and chemosensitization target of interest. We have identified Cleft Lip and Palate Transmembrane 1-Like (CLPTM1L)/Cisplatin Resistance Related Protein 9 (CRR9) as an ER stress related mediator of cytoprotection in pancreatic cancer. We recently demonstrated that CLPTM1L is highly expressed in pancreatic ductal adenocarcinoma and associated with poor outcome.

Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models.

Background: Patient-derived tumor models are the new standard for pre-clinical drug testing and biomarker discovery. However, the emerging technology of primary pancreatic cancer organoids has not yet been broadly implemented in research, and complex organotypic models using organoids in co-culture with stromal and immune cellular components of the tumor have yet to be established. In this study, our objective was to develop and characterize pancreatic cancer organoids and multi-cell type organotypic co-culture models to demonstrate their applicability to the study of pancreatic cancer.

Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines.

Regulator of G Protein Signaling (RGS) 17 is an overexpressed promoter of cancer survival in lung and prostate tumors, the knockdown of which results in decreased tumor cell proliferation in vitro. Identification of drug-like molecules inhibiting this protein could ameliorate the RGS17's pro-tumorigenic effect. Using high-throughput screening, a chemical library containing natural products was interrogated for inhibition of the RGS17-Gα interaction.

Novel Anti-CRR9/CLPTM1L Antibodies with Antitumorigenic Activity Inhibit Cell Surface Accumulation, PI3K Interaction, and Survival Signaling.

We and others have recently shown cisplatin resistance-related protein 9 (CRR9)/Cleft Lip and Palate Transmembrane 1-Like (CLPTM1L) to affect survival and proliferation in lung and pancreatic tumor cells. Our research has indicated that CLPTM1L affects multiple survival signaling pathways in tumor cells under oncogenic, genotoxic, and microenvironmental stress. We have confirmed the association of CLPTM1L with pancreatic cancer by demonstrating overexpression of CLPTM1L in pancreatic tumors and poor survival in patients with high tumor expression of CLPTM1L.

A novel, soluble compound, C25, sensitizes to TRAIL-induced apoptosis through upregulation of DR5 expression.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential therapeutic agent that induces apoptosis selectively in tumor cells. However, numerous solid tumor types are resistant to TRAIL. Sensitization to TRAIL has been an area of great research interest, but has met significant challenges because of poor bioavailability, half-life, and solubility of sensitizing compounds such as curcumin.

CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis.

The transmembrane protein CLPTM1L is overexpressed in non-small cell lung cancer, where it protects tumor cells from genotoxic apoptosis. Here, we show that RNA interference-mediated blockade of CLPTM1L inhibits K-Ras-induced lung tumorigenesis. CLPTM1L expression was required in vitro for morphologic transformation by H-RasV12 or K-RasV12, anchorage-independent growth, and survival of anoikis of lung tumor cells.

Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus.

Cleft Lip and Palate Transmembrane Protein 1-Like (CLPTM1L), resides in a region of chromosome 5 for which copy number gain has been found to be the most frequent genetic event in the early stages of non-small cell lung cancer (NSCLC). This locus has been found by multiple genome wide association studies to be associated with lung cancer in both smokers and non-smokers. CLPTM1L has been identified as an overexpressed protein in human ovarian tumor cell lines that are resistant to cisplatin, which is the only insight thus far into the function of CLPTM1L.

Is there a role for bi-atrial pacing resynchronisation therapy in the management of drug-refractory atrial fibrillation in patients unsuitable for left atrial ablation?

Background: This retrospective cohort study evaluated whether long term outcome of atrial resynchronisation therapy using bi-atrial pacing (BiaP) to treat atrial fibrillation (AF) was effective in patients deemed unfit for left atrial (LA) ablation procedures.

Methods And Results: The patient population comprised 2 groups: those deemed suitable for left LA ablation (n=14) and those who were not (n = 17). Both groups underwent BiaP and outcomes were evaluated by comparing symptoms, AF duration, admissions and antiarrhythmic drugs (AAD) for an equal period of time pre and post implantation.

Dietary administration of berberine or Phellodendron amurense extract inhibits cell cycle progression and lung tumorigenesis.

Phellodendron amurense extract is a Chinese herbal remedy that has recently been studied for its antitumor, antimicrobial and other biological activities. It is previously unknown if these agents are bioavailable and effective against tumors when delivered as a dietary component. It is also unknown if the anti-tumorigenic properties of berberine, an isoquinoline alkaloid component of P.

Do statins improve heart failure outcome in post-myocardial infarction patients with moderate to severe left ventricular dysfunction?

The authors conducted this retrospective cohort study to assess the influence of statins on heart failure (HF) outcome by enrolling 500 consecutive acute myocardial infarction patients, majority (339 of 500) with moderate to severe left ventricular dysfunction (ejection fraction <40%) between March 2000 and March 2002 with 5.5-year mean follow-up. They were retrospectively analyzed according to whether they were discharged on a statin, and their HF outcome was evaluated independent of overt clinical ischemic events.

Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1.

Recent genome-wide association studies have linked the chromosome 15q24-25.1 locus to nicotine addiction and lung cancer susceptibility. To refine the 15q24-25.

RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.

We have identified RGS17 as a commonly induced gene in lung and prostate tumors. Through microarray and gene expression analysis, we show that expression of RGS17 is up-regulated in 80% of lung tumors, and also up-regulated in prostate tumors. Through knockdown and overexpression of RGS17 in tumor cells, we show that RGS17 confers a proliferative phenotype and is required for the maintenance of the proliferative potential of tumor cells.

Does atrial fibrillation beget ventricular fibrillation in patients with acute myocardial infarction?

Background: Atrial fibrillation (AF) is associated with increased mortality and a higher complication rate postmyocardial infarction (MI), but the exact mechanisms are unknown. We investigated whether AF predisposes to ventricular arrhythmia in postmyocardial infarct patients, thereby accounting for increased mortality.

Methods: Five hundred consecutive patients admitted to our coronary care unit with acute MI were monitored for in-hospital arrhythmias.

Use of a retained guidewire to improve the left ventricular pacing threshold.

Although transvenous access to the coronary veins has considerably simplified left ventricular (LV) pacing, it can remain a time consuming and arduous task achieving satisfactory pacing positions for the LV electrode. Common problems include negotiating small veins with adequate guide catheter stability, pacing electrode stability once positioned, and phrenic nerve stimulation. We report a case where use of the pacing lead guidewire resulted in a dramatic reduction in the pacing threshold of the LV lead, and saved the patient the need to undergo thoracotomy placement.

HPV16-E6 associated hTERT promoter acetylation is E6AP dependent, increased in later passage cells and enhanced by loss of p300.

The E6 oncoprotein from high-risk HPV types activates human telomerase reverse transcriptase (hTERT) transcription in human keratinocytes. Studies on how E6 regulates hTERT have implicated E-box or X-box elements in the hTERT promoter (Veldman et al., Proc Natl Acad Sci USA 2003;100:8211-14; Oh et al.

Human papillomavirus type 16 E6 activates NF-kappaB, induces cIAP-2 expression, and protects against apoptosis in a PDZ binding motif-dependent manner.

Infection with human papillomavirus (HPV) is a critical factor in the pathogenesis of most cervical cancers and some aerodigestive cancers. The HPV E6 oncoprotein from high-risk HPV types contributes to the immortalization and transformation of cells by multiple mechanisms, including degradation of p53, transcriptional activation of human telomerase reverse transcriptase (hTERT), and degradation of several proteins containing PDZ domains. The ability of E6 to bind PDZ domain-containing proteins is independent of p53 degradation or hTERT activation but does correlate with oncogenic potential (R.