Overall, very few functional imaging studies were available on Torin 1 nmr cognitive flexibility (see Table 4). While SAs (cocaine-dependent subjects) showed decreased activation during a cognitive flexibility task in the anterior cingulate gyrus, medial PFC, and subcortical regions (thalamus and lentiform nucleus), no differences were found in lateral prefrontal cortices (DL and

anterior frontal) compared with HCs. During an attention task, however, Inhibitors,research,lifescience,medical decreased DL (and VM) PFC as well as ACC, and medial frontal gyrus activation was found in SAs (cocaine) compared with HCs, but activation patterns between smokers and HCs did not differ during planning. General Discussion A number of converging findings emerged in key brain regions during Inhibitors,research,lifescience,medical specific tasks, including increased activation in the limbic system following cue-reactivity paradigms, and increased DLPFC and PFC activity in cognitive and motor impulsivity studies, respectively. However, there were also several inconsistencies, which can probably be explained by methodological differences with regard to tasks and protocols used, study population, imaging modalities, and data analysis. Whereas we discussed these possible explanations in each section separately, in this section

we will discuss some general issues in neuroimaging Inhibitors,research,lifescience,medical research and provide an outline for future research. Unfortunately, as mentioned before, only few studies are available on executive functioning, precluding assessment of common findings and inconsistencies in these areas. Also, two previous reviews concluded Inhibitors,research,lifescience,medical that there was reduced anterior and posterior cingulate activation, and reduced inferior frontal, DLPFC, and parietal activation during process-related functioning, but these studies were limited to cocaine and (meth-)amphetamine users (Hong et Inhibitors,research,lifescience,medical al. 2009; Gu et al. 2010). Both reviews are very similar in their conclusions regarding differences between users and controls: both proposed that altered brain activation patterns are related to the demand-specific processing of

information, rather than generic differences between stimulants users and controls. In addition, both reviews also conclude that these differences are consistent with a shift to more stereotyped, of habitual behavior. The findings of this review appear to fit rather well a number of aspects of different but partly overlapping theories of drug addiction. Reward and punishment-, motor impulsivity-, and cue-reactivity imaging studies support a role for the I-RISA model: impaired prefrontal functioning that may play a key role in inadequate evaluation of natural reinforcers and in impaired response inhibition, while limbic dysregulation (e.g., amygdala overactivation) would reflect increased valuation of drug stimuli.

Further studies are necessary to elucidate the regulatory mechanism of protein O-mannosylation. Three other types of protein O-glycosylation are initiated in different ways. O-GalNAc glycosylation is the most common protein-modification and is initiated

by the action of a family of pp-GalNAc-Ts. So far, no consensus sequence has emerged that is both necessary Inhibitors,research,lifescience,medical and sufficient for O-GalNAc glycosylation to occur. Many nuclear and cytosolic proteins are O-GlcNAc glycosylated, but a consensus sequence for O-GlcNAc transferase has not been reported. On the other hand, O-Fuc glycosylation exists in direct O-linkage to Ser or Thr residues in two different types of Cys-knot motifs: epidermal growth factor-like (EGF) repeats and thrombospondin type 1 repeats (TSR). The enzyme responsible for adding O-Fuc to EGF repeats was identified as protein O-fucosyltransferase 1 (POFUT1) and the enzyme for adding to TSR was identified as POFUT2 (19, 20). A consensus sequence for O-Fuc glycosylation in EGF is proposed CysX4–5(Ser/Thr)Cys between Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical the second and third Cys residues and a consensus sequence for O-Fuc in

TSR is TrpX5CysX2/3Ser/ThrCysX2G between the first and second Cys residues, respectively. Both POFUT1 and POFUT2 require a specific sequence for O-Fuc glycosylation. Glycosylation is basically controlled by the combined action of each glycosyltransferase. However, recent studies indicate that glycosylation Inhibitors,research,lifescience,medical is regulated in a complicated manner. Glycosyltransferase activities are regulated by other factors or by complex formation.

For example, human core 1 β3-galactosyltransferase activity www.selleckchem.com/products/SRT1720.html requires the expression of Cosmc (21). Cosmc is a molecular chaperone that specifically assists the folding/stability of core 1 β3-galactosyltransferase and is required for a glycosyltransferase expression. Mutations of COSMC were recently found in patients with Tn syndrome who could not produce core 1 structure (Galβ1-3GalNAc) Inhibitors,research,lifescience,medical (22). Another glycosyltransferase with complex regulation is human chondroitin synthase, which cannot polymerize chondroitin sulfate in vitro; rather its activity requires the coexpression of chondroitin polymerizing factor (23). As a third example, the bifunctional glycosyltransferases EXT1 and EXT2, which polymerize heparan sulfate, need to form a hetero-oligomeric complex to exert their optimal catalytic activities and to exist in the appropriate intracellular locations (24). We observed that protein O-mannosylation almost can be initiated by direct complex-formation of POMT1 and POMT2, but not by either enzyme by itself. POMT1 or POMT2 are thus different from EXT1 and EXT2 because the latter enzymes are active by themselves. One possibility is that formation of the POMT1-POMT2 complex creates a new catalytic domain (15). Further studies are needed to elucidate the mechanism of complex formation between POMT1 and POMT2, and the regulation of O-mannosyltransferase activity.

15 Most biological treatments in psychiatry- probably follow this path already. For example, monoamine reuptake inhibitors benefit many patients with depression by increasing serotonergic and/or noradrenergic neurotransmission, but probably not by correcting an underlying monoaminergic deficit, for which little evidence has been found.16,17 Similarly, current lesion surgery and DBS approaches for depression or obsessive -compulsive disorder (OCD), whose targets all converge onto pathways from brain stem and basal ganglia to prefrontal cortex,18 work through—hitherto poorly understood—effects on the function of these pathways in motivation

and emotion regulation, but Inhibitors,research,lifescience,medical not necessarily- because there are documented primary abnormalities in these pathways. Regarding neurofeedback, this NVP-LDE225 order implies that clinical benefits may be obtained from self-regulation training that activates compensatory circuits Inhibitors,research,lifescience,medical for particular cognitive processes (eg, emotion regulation) or inhibits circuits that, although normal when viewed in isolation, contribute to dysfunction in the context of the patient’s primary pathology.

For example, it may be beneficial to suppress canonical thought processes such as self-comparison Inhibitors,research,lifescience,medical in the context of a depressive disposition. The great progress in the understanding of the circuits of cognitive, affective, and social information

processing made through the last two decades of functional Inhibitors,research,lifescience,medical imaging can thus inform the design of imaging-based clinical neurofeedback protocols, even in the absence of primarily abnormal imaging signals. Applications in depression Symptoms of depression can be broadly grouped into the four domains of emotion regulation, cognition, motivation, and homoeostasis (Table I).19 Although like all categorization of psychological phenomena, this classification is somewhat artificial (and some symptoms map onto more than one category), it can help the search Inhibitors,research,lifescience,medical for the biological mechanisms of depression.20 Furthermore if the neural systems underlying some of these functional clusters Farnesyltransferase prove to be modifiable (by pharmacological, psychological, or physical intervention) they may become viable targets for new antidepressant therapies. Table I. Symptoms of depression. Five symptoms are required over a 2-week period for an episode of major depression (DSM-IV). ICD-10 defines depressive episodes by a combination of the most typical (printed in bold face) and other symptoms.19 The number of symptoms … New therapeutic strategies for depression are sorely needed. Depression is expected to assume the first place in the WHO’S global disease burden statistic by 2020. It affects up to 15% of the population of industrialised countries.

In general, IO and TrA muscles have anatomical similarities in that both are among the muscles comprising the structure of the lower abdominal wall and they have similar functions. However, unlike the TrA, the IO affects the spine because of its direction.4 The IO attaches

to the posterior layer of the thoracolumbar fascia. Contraction of this muscle creates a lateral tension force on the thoracolumbar fascia, which creates the intrinsic translational and rotational stabilization of the spinal unit.20 This should be a reason for the higher activation of this muscle during the bird-dog position. Also, Huang23 stated that the unilateral multifidus activation increased in the bird-dog Inhibitors,research,lifescience,medical position. Inhibitors,research,lifescience,medical Because the body weight is supported by one knee and elbow in the bird-dog position, which is an unstable status, the torque of the arm and leg is greater and the multifidus muscle shows a higher activation potential. On the other hand, lumbar multifidus and erector spine muscles have a relatively high proportion of type 1 (slow twitch)

muscle fibers, which makes them well-suited for endurance or sustaining contraction activities. During the bird-dog exercise, these muscles produce EMG signal amplitudes of 29% maximal isometric voluntary contraction (MIVC).23 According to Arokoski,16 Inhibitors,research,lifescience,medical in the bird-dog exercise with weights on the hand, unilateral leg extension, and unbalanced limb movements, there is an increase in the trunk muscle activation, which contributes to the preservation of the spinal

stability. Inhibitors,research,lifescience,medical The increase in the activation of left IO and left and right multifidus muscles in the bird-dog exercise may be related to the unstable body position. Accordingly, the core muscles are recruited for proprioception, balance, and energy transfer from the lower extremity to the upper extremity and hold a neutral abdominal posture.24 In the present study, the left TrA activation in left leg extension was higher than that in right arm extension. Callaghan reported that in order to reduce loads on the spine in exercises such as leg extension with the Inhibitors,research,lifescience,medical spine being held isometrically, the trunk muscles exhibited asymmetrical activity.25 In single leg extension, while the subject is others on the hands and knees, he/she produces mild extensor activity and lower spine compression less than 2005 N. Raising the contralateral arm (bird-dog) increases extensor muscle activation and also spine compression to more than 3000 N. Sufficient stability is ensured with mild abdominal bracing.26 According to a Selleck JQ1 recent study, the reciprocal index of the TrA depended on the magnitude and direction of perturbation, refuting the “corset hypothesis” as a normal mechanism for the TrA prior to arm movement. Therefore, the feed-forward activity of the TrA is asymmetric and depends on the direction of perturbation due to arm movement.

Also the understanding of antideprcssantinduced processes has greatly increased in the past years (eg, ref 30). A summary of animal models of depression that are classified according to type and sensitivity to chronic drug treatment is presented in Table /.According to Willner and Mitchell,31 the diathesis models summarize those paradigms that involve a genetically determined predisposition for the depressive illness, whereas in mere stress models external stimuli are the only factors triggering changes in behavior and physiology. Social dominance models are those that use natural (social) stressors and arc considered as a subset of the stress Inhibitors,research,lifescience,medical models. Table I. Animal models

of depression. Many of the paradigms Inhibitors,research,lifescience,medical addressed above are more correctly described as models of stress rather than models of depression. Not all responses to stress are maladaptive, because the stress response may also fulfill adaptive or protective functions. Therefore, to truly model depression, other factors such as the genetic background that might cause a predisposition for the disease must also be taken into consideration. However, studies looking at stressful Inhibitors,research,lifescience,medical early life experiences and the type of stressresponsiveness later in life highlight a key area. They may help to understand the processes that in conjunction with environmental stress can lead to depression in some individuals but

Inhibitors,research,lifescience,medical not in others. With the emergence of specific genetic factors more defined models may be created in the near future. In the case of major depressive illness, we know that genetic factors can only account for about 30% of the variance, and environmental factors clearly play a major role in inducing the illness.32 However, the development of models of depression based on the interaction between stress and genetic vulnerability appears plausible. Generation of specific strains or lines of rats or mice

may be advantageous. Studies in knockout models with a mutation in a single gene Inhibitors,research,lifescience,medical may be of limited usefulness because of confounding factors such as developmental adaptational processes. Conditional knockouts may be considered as an improvement, but they also can inform us only about the role of a single gene. Therefore, the more complex models involving the interaction of genes and environment could supposedly yield more useful information. Validity of animal models The importance ALOX15 of chronic drug treatment Pharmacological tests and models sensitive to acute drug treatment are not included in this overview. These models, perhaps more appropriately called “screens,” 33 have been designed to detect most existing antidepressants. The mechanism(s) of action by which test learn more compounds produce positive results in such screens may not be identical, or even not similar to the mechanisms underlying their clinical effects.

To the editor, Dr. Takatori and colleagues deserve praise for meticulously studying the extent and severity of upper gastrointestinal (GI) complications in 91 inoperable pancreatic cancer patients treated on a prospective clinical trial with proton-based radiotherapy and concomitant gemcitabine chemotherapy (GPT) (1). The significant complications observed in this series (49.4% rate of gastric/duodenal ulceration), however, starkly contrast the Inhibitors,research,lifescience,medical favorable toxicity profile we observed in our series of pancreatic cancer patients treated with proton therapy and concomitant capecitabine chemotherapy (2). In our series, we observed no grade 3 IWR-1 toxicities in patients

receiving proton doses ranging from 50.40 to 59.40 Cobalt Gray Equivalent (CGE) at 1.8 CGE per daily fraction with daily oral capecitabine Inhibitors,research,lifescience,medical (1,000 mg twice daily). The median weight loss during treatment was only 1.3 kg (1.75% of body weight). Additionally, when radiotherapy plans avoided the use of anterior or left lateral

fields—reducing small bowel and gastric exposure—grade 2 GI toxicity was eliminated and median weight loss was only 0.5 kg. Possible explanations for the disparity of outcomes between these two series might include: (I) aggressive radiotherapy doses [67.5 Gray equivalent (GyE)] and high dose per fraction (2.7 GyE) delivered in the GPT series; (II) concomitant delivery of full-dose gemcitabine Inhibitors,research,lifescience,medical (800 mg/m2 on days 1, 8, and 15), well-recognized as a potent radiosensitizing agent; and (III) radiotherapy fields expanded to include regional lymph nodes in addition to the primary tumor. Although details of the radiotherapy Inhibitors,research,lifescience,medical plans were not included in the GPT publication, it is possible that some of the toxicity might have been mitigated if anterior and left lateral fields had Inhibitors,research,lifescience,medical been avoided or the dose delivered through such fields was minimized. While the current study is well-designed and well-reported, it would be wrong to conclude that proton therapy for patients with pancreatic cancer is associated with a high rate of gastrointestinal toxicity. Indeed, we have every reason to believe,

based on its superior dosimetry (3), that proton therapy offers significant improvements in the therapeutic index compared to X-ray-based therapies such as intensity-modulated PAK6 radiotherapy. Our clinical experience helps confirm the hypothesis, based on this dosimetry, that proton therapy reduces GI toxicity and may allow for treatment intensification—although perhaps not to the same degree as the intensification offered on the GPT protocol. We appreciate you taking the time to consider our letter and look forward to hearing from you in the future. Acknowledgements Disclosure: The authors declare no conflict of interest.
While pancreatic cancer remains an almost uniformly fatal diagnosis, data suggest that advances in treatment have resulted in modest gains in overall survival for local (1,2) and metastatic (2,3) disease.

These observations, coupled with my lack of confidence in PDE-5 inhibitors as a useful on-demand solution for erections during the first year of recovery after prostatectomy, have led to my preferential use of MUSE as part of a penile rehabilitation program. I think MUSE RP-01

would have been even more informative if patients had been given Inhibitors,research,lifescience,medical both MUSE at the 1000-µg dose and/or sildenafil at the 100-mg dose for on-demand intercourse. I anecdotally witnessed 60% on-demand success with 250 µg of MUSE during RP-01. This is the success rate typically reported with much higher doses of MUSE, so I suspect such a higher dose would have shown even higher success within the confines of a trial. Herbert Lepor, MD: There are men who do not achieve an erection with PDE-5 inhibitors during the early recovery phase after RP. Many of these men will not embark on a

penile injection regimen. For these men, MUSE is an excellent alternative for achieving erections adequate for intercourse. I believe it is underutilized in the management of post-RP ED. What is the mechanism Inhibitors,research,lifescience,medical for MUSE in penile rehabilitation? Andrew McCullough, MD: Costabile and colleagues30 evaluated the erectile response to intraurethral Inhibitors,research,lifescience,medical PGE1 in 384 men with ED after RP, with treatment beginning no less than 3 months after surgery. This was a multi-institutional study before the approval of PDE-5 inhibitors Inhibitors,research,lifescience,medical and included men at differing times from surgery and with both NSRRP and NNSRRP. Initial doses were 125 or 250 µg, which were increased to 500 or 1000 µg if the erectile response was inadequate. When treatment was administered in the clinic, 70% of the participants developed an erection sufficient for intercourse. These Inhibitors,research,lifescience,medical subjects were then randomized to a 3-month at-home trial with either PGE1 or placebo. During this phase 57% of the PGE1 subjects had successful intercourse at least once at home, compared to an intercourse rate of 6.6% of men treated with placebo. These rates compare favorably with PDE-5 inhibitor response rates in younger men

with bilateral NSRRP. Adverse events included penile pain and urethral pain/burning. This placebo-controlled study supported the use of a less invasive treatment modality in men who might not otherwise respond to PDE-5 inhibitors. More recently, Raina and coworkers31 reported the results of a study in 54 GW4064 supplier prostatectomized men who used transurethral PGE1 (250, 500, or 1000 µg). Subjects old experienced ED for at least 6 months after surgery before initiating treatment. Fifty-five percent of the subjects were able to achieve and maintain erections sufficient for intercourse while on treatment, and 48% continued long-term therapy with a mean use of 2.3 years. There were no significant differences in responses between those subjects who had a nerve-sparing surgery (34 patients) and those who had a NNSRRP procedure (20 subjects).

” Such information is crucial, as it suggests that potentially iatrogenic find protocol mechanisms (eg, frustration with treatment progress; demands on family time) may be introduced when interventions

are introduced in the real world. Of course, rather than posing an intractable problem, such findings provide fertile ground for further mechanistic intervention research to identify, specify, isolate, and modify these newly found mechanisms. Conclusion This provides, then, a window into the future of psychosocial Inhibitors,research,lifescience,medical intervention research for ASD. It is an environment in which basic research and applied practice are reciprocally informed. It is a setting where basic questions of mechanism and process may be used to build progressively more targeted, optimized, and responsivelydesigned treatments. Most importantly, it is a world where families and individuals with ASD may find hope for rapid

and Inhibitors,research,lifescience,medical effective treatment of social-communicative deficits among a rich array of individually tailored, empirically supported, ever-evolving psychosocial interventions which are tethered to specific and measureable mechanisms affecting the Inhibitors,research,lifescience,medical sought change. Acknowledgments Preparation of this manuscript was partially supported by Fellowships from the American Psychological Foundation, Jefferson Scholars Foundation, and International Max Planck Research School, and grants from the American Psychological Association and Association for Psychological Science to Matthew D. Lerner. James C McPartland was supported by NIMH K23MH086785, NIMH R21MH091309 Inhibitors,research,lifescience,medical and a NARSAD Atherton Young Investigator Award.
Autism was originally defined by Leo Kanner in 1943 as an innate inability to create normal, biologically determined, emotional contact with others. The primacy of the social deficit is widely recognized, and lack of social reciprocity is a central part of the diagnosis. Beyond that, there have been great changes in the past decade in the conceptualization of autism and related disorders,

eventually reflected in the draft of the fifth edition of the Diagnostic and Statistical Manual of Inhibitors,research,lifescience,medical Mental Disorders (DSM-5, www.dsm5.org). Indeed, proposed revisions of the precedent edition of the manual (DSM IV-TR)1 include the combination of specific DSM-IV-TR diagnoses into a single broad autism spectrum disorder (ASD), and the identification of two domains of impairment (social communication and interaction, and restricted Idoxuridine repetitive behavior) instead of three (social interaction, communication, and restricted repetitive and stereotyped patterns of behavior, interests and activities). These issues are discussed in detail by Volkmar et al in this issue of the journal. Because of the high heritability estimates in autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes.

These signals activate microglia to release free radicals and proinflammatory cytokines, and in turn, cause

further motor neuron stress and initiate a self-propagating cytotoxic cascade. A greater understanding of the bidirectional signaling between motor neurons and microglia may lead to therapies that can restore the imbalance between neuroprotection and cytotoxicity. Figure 2. Major themes in ALS pathogenesis. Acknowledgement Supported by grants from the Muscular Dystrophy Association and the NIH.
The jaw ROM exercise with a hot pack and massage of masseter were effective for occlusal force increase in DMD. The greatest occlusal force was significantly higher 6 months after Inhibitors,research,lifescience,medical the jaw ROM exercise than at the start. Furthermore, the jaw ROM Inhibitors,research,lifescience,medical exercise reduced patients’ fatigue during a meal and gave patients a feeling of satisfaction. We report the effect of this jaw ROM exercise. Muscle atrophy in DMD progresses with age, and muscle atrophy is not restored naturally. Also, in the muscle involved in deglutition, muscle atrophy is irreversible without exception. Deglutition is DAPT secretase divided into four phases, the preparation, oral, pharynx, and esophageal phases

(1). Food is cut into small pieces in the buccal cavity, and mixed with saliva to form an alimentary bolus in the preparation phase. Inhibitors,research,lifescience,medical The formed alimentary bolus is transported to the pharynx in the oral phase. In the pharynx phase,

Inhibitors,research,lifescience,medical the alimentary bolus progresses from the buccal cavity to the pharynx and transfers to the esophagus. In the esophagus phase, the alimentary bolus is transported to the stomach by peristalsis. Many muscles are involved in these phases. According to a previous study on dysphagia in DMD, disturbance in the preparation and oral phases (the preparation/ oral phase) is already apparent in patients in their teens (2). As patients reach their 20s, they show disturbance in the pharynx phase (3, 4). In the preparation/ oral phase in DMD, decreased occulusal force, malocclusion, macroglossia, and lingual muscle weakness are observed. The occlusal Inhibitors,research,lifescience,medical force of DMD patients in their teens is markedly lower than that of healthy persons of the same age (5). Biting disorder causes loss of appetite, fatigue during meals, and nutritional deficiencies. Moreover, the pleasure of eating is diminished. Therefore, measures against these problems should be taken when patients are still in of their teens. However, no report was available that was related to interventions in biting disorder in DMD. The main causes of biting disorder in DMD are a decreased occlusal force and malocclusion. For malocclusion, forward incisors and posterior molar apertognathia are generally common (6, 7). The therapy for the malocclusion should be orthodontic or orthogonathic in general. However, such therapies are not necessarily applicable to DMD patients.

9 Since Albright’s novel statement in 1941 about the humoral nature of tumor hypercalcemia,10 #Tasocitinib randurls[1|1|,|CHEM1|]# many efforts have been made to prove the secretion of either ectopic PTH

or a substance that has functional similarity to PTH. The enthusiasm and the ensuing hard work led to the discovery of PTHrP in 1988,11 which was a turning point in the correct interpretation of tumor hypercalcemia.12 In an extensive review of the literature we could find 42 patients with pancreatic NET and hypercalcemia. Clinical and laboratory data of the reviewed cases as well as the present case are shown in table 1. The patients are 20 men and 22 women with a mean age of 45 years (age range 8-77 years). Inhibitors,research,lifescience,medical The largest size of the tumor was 3.9-18 cm with a mean of 10.2 cm. All patients were hypercalcemic with serum calcium concentrations ranging from 10.6-26.4 mg/dl with a mean of 15.5 mg/dl. Serum concentrations Inhibitors,research,lifescience,medical of PTH were low or undetectable in 31 cases, and within normal range in 11 cases. Of 25 patients whose serum PTHrP had been measured, 24 had elevated levels ranging from 2.3-40 pmol/L with a mean of 10.8 pmol/L, which was about 10 times the upper limit of normal range. Data for IHC, available for 17 patients, showed positivity for PTHrP in all except for two cases.13 chromogranin

(CgA), synaptophysin (Syn), neuron specific enolase (NSE), somatostatin (So) and calcitonin (Cal) were Inhibitors,research,lifescience,medical positive in varying combinations in all cases except two.14 Moreover, KI 67 in those who were analyzed was less than 10%, which was in agreement with the low growth rate and Inhibitors,research,lifescience,medical long survival of those patients. Table1 Clinical and laboratory data of 42 patients with pancreatic neuroendocrine tumor and hypercalcemia Surgical removal of the tumor was the main therapeutic option. However, complete removal of the tumor could be done in only seven cases because of multiple liver metastasis, local invasion and hypervascularity of the tumors. Indeed multiple liver metastases were seen in 80 % of the patients. Inhibitors,research,lifescience,medical In these cases, distal pancreatectomy and/or debulking were done. Due to such limitations

for surgery, nonsurgical treatment modalities are of utmost significance. Somatostatin analogues have been used in patients with NET for the last two decades. Their alleviating effects on hypercalcemia as well as their potential anti tumor effects have also been reported. In last couple of years, Sandostatin LAR or similar analogues have been mafosfamide used in almost all cases in which complete surgical removal of the tumor has been impossible. It should be noted that anti proliferative effects of the drug is weak, and in some cases the tumor has progressed with time.15,16 Interferon α is another biotherapeutic agent approved for patients with NET. A previous study,16 reported that it was effective in reducing serum calcium and maintaining normocalcemia for a period of six months.