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Angiogenesis and Anti-tumor Immunity in the Tumor Microenvironment: Opportunities for Synergism in Intervention

Author: Christopher Lemmon, Ibrahim Sadek, Zhonglin Hao

Manuscript ID: JNSCI#17-0623


Success of angiogenesis inhibition has met with resurgence of immunomodulation in treatment of metastatic carcinomas. While each of these is effective in some cases, the response rates are low, and resistance soon emerges to single agent treatment. Will combination of the two improve response rate and duration of response through synergy? In addition to blocking neovascular formation, angiogenesis inhibitors (AI) help deliver more effective cytotoxic T lymphocytes to the tumor by improving vascular perfusion. Recent studies also showed that AI not only increased the efficacy of effector immune element but also decreased the number and function of suppressor immune cells such as T-regulatory cells, myeloid-derived suppressor cells or tumor-associated macrophages. In this review, we focus on AI and their effects on antitumor immunity in the tumor microenvironment and their potentials in boosting the efficacy of immunotherapy. In the clinical arena, trials are at the early stage to gauge the feasibility and preliminary signs of synergy.



Pathways to Genome-targeted Therapies in Serous Ovarian Cancer

Author: Joshua Axelrod and Joe Delaney

Manuscript ID: JNSCI#17-0611


Genome sequencing technologies and corresponding oncology publications have generated enormous publically available datasets for many cancer types. While this has enabled new treatments, and in some limited cases cures, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.



Military blast-induced synaptic changes with distinct vulnerability may explain behavioral alterations in the absence of obvious brain damage

Author: Catherine M. Parisian, Gregory Georgevitch, Ben A. Bahr

Manuscript ID: JNSCI#17-0607


Sadly many military veterans, who left home to serve their country honorably, return from
service with permanent life-changing injuries. It is easy to remember our debt to those who have
incurred such visible injuries, and all too easy to forget the invisible wounds that afflict so many
of our military servicemen and women. Brain injuries can be invisible during initial medical
evaluations and are often caused by military explosives that create blast shockwaves of varying
intensity. One of the most common types of traumatic brain injury (TBI) linked to military
service is blast-induced neurotrauma. To better understand this type of injury, a recently
published study subjected rat brain slice cultures to detonations of RDX military explosives,
resulting in synaptic alterations that may underlie the behavioral changes in those TBI sufferers
who do not exhibit measurable brain damage. Such research has the potential to improve
diagnoses by identifying indicators of synaptic integrity for the assessment of subtle
synaptopathogenesis linked to blast-induced neurotrauma.



Acromegaly: Underdiagnosed in patients with prolactinomas

Author: Ekaterina Manuylova, G Edward Vates, Ismat Shafiq

Manuscript ID: JNSCI#17-0602


Acromegaly is a rare disease with mortality rates 2-3 times higher as compared to the general population. The interval from onset of symptoms to the diagnosis may range from one year to several decades. The disease remains under-diagnosed despite improved diagnostic technologies. It is usually a sporadic disease but can be familial in several genetic syndromes, for example, MEN-1, MacCune-Albright syndrome, Carney complex and familial isolated pituitary adenoma. Prolactin secreting pituitary adenoma has been known to co-secrete growth hormone. Review of the literature suggests that up to 4% of patients with prolactinoma can develop acromegaly. Current literature suggests IGF-1 measurement for all prolactinoma patients at the initial diagnosis. Afterwards, bio-chemical screening is not routinely performed per the guidelines; as a result mild cases of acromegaly can be missed. Therefore, routine screening for GH excess should be considered in patients with prolactinoma diagnosis on a regular basis.


Medical Sciences

Vancomycin in the treatment of Primary Sclerosing Cholangitis: A Review

Author: Sukhpreet Singh, Kusum K. Kharbanda

Manuscript ID: JNSCI#17-0419


Primary sclerosing cholangitis (PSC) is a disease of the bile ducts that causes inflammation and destruction of the intra- and/or extra-hepatic bile ducts. It is also a progressive disorder that leads to fibrosis and liver failure and also increases risk of malignancy. PSC is a heterogeneous disease that is often associated with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). As of now, there is no established medical therapy for PSC and a majority of patients will eventually require liver transplantation. PSC is the fifth leading cause for liver transplantation, but transplantation does not guarantee a cure since there is a 20% chance of disease recurrence in the graft. At present the mainstay of therapy is ursodeoxycholic acid (UDCA) which has largely been studied in various randomised control trials but has failed to alter the long-term outcome and natural course of the disease. Pathogenesis of PSC is still not clearly understood but recent advances in understanding the pathogenesis have paved way for trial of new therapeutic agents. Here in this review article, we present information gathered from published case reports/series and randomised control trials on the relationship between the microbiota and PSC pathogenesis with a purpose of understanding whether vancomycin is a potential effective pharmacotherapy for patients with this disease.

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