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Cognitive and Psychosocial Improvements Following Aripiprazole Augmentation of SSRI Antidepressant Therapy in Treatment Refractory Depression: A Pilot Study

Cognitive and Psychosocial Improvements Following Aripiprazole Augmentation of SSRI Antidepressant Therapy in Treatment Refractory Depression: A Pilot Study

aripiprazole increases the likelihood of remission (Berman et al., 2009; Nelson et al., 2012). It is well-tolerated, even after long- term (e.g., a year) administration, with primary side effects being weight gain, akathisia, and fatigue (Berman et al., 2011). However, the ability for aripipriazole to address specific func- tional outcomes has been sparsely investigated. Thase et al. (2008) examined mean changes in the Sheehan Disability Scale (SDS) scores between depressed individuals augmented with aripiprazole vs. placebo and found that aripiprazole augmenta- tion was associated with significantly greater reductions in mean SDS scores, as well as with the individual items measur- ing symptom interference with social and family life. The effect of aripiprazole augmentation on health-related quality of life and health utility has been compared to augmentation with other atypical antipsychotics based on data from the National Health and Wellness Survey, and aripiprazole augmentation showed significantly greater benefits in measures of mental health, general health, emotional role limitations, bodily pain, and health utility (Kalsekar et al., 2012). To our knowledge, no study has examined cognitive changes as an outcome following aripiprazole augmentation. Reimherr et al. (2010) conducted a pooled analysis examining symptom-level improvements in core symptoms of depression as measured by the Montgom- ery-Asberg Depression Rating Scale (MADRS) and the Inven- tory for Depressive Symptomatology, Self-Report (IDS-SR). They did not find that aripiprazole augmentation was superior to placebo augmentation on concentration symptoms as meas- ured by the items addressing that symptom on either scale; however, it is not clear how many participants endorsed con- centration difficulties at baseline.
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Combination rapid transcranial magnetic stimulation in treatment refractory depression

Combination rapid transcranial magnetic stimulation in treatment refractory depression

medication trials was approximately 8.5. Both the Sham and Combination treatment arms showed improvement with time although there was no clear treatment effect for active rTMS. The one clinical variable that did appear to have a significant effect on response was an improved response with a decreased number of previous failed medication trials. This finding is not surprising and may be a measure of treatment resistance. In addition this observation is similar to data from ECT studies (eg, Sackeim et al 1990), which correlates poor response to ECT with previous medication failures. The fact that a previous poor response to ECT was not associated with poor response to rTMS replicates earlier work that showed that subjects may respond differentially to ECT and rTMS (Janicak et al 2002). It is also noteworthy that there were no differences in neuropsychological functioning across the sham and the active arms, suggesting the relative safety of both rTMS procedures over the 10-day treatment period.
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The co administration of quetiapine or placebo to cognitive behavior therapy in treatment refractory depression: A preliminary trial

The co administration of quetiapine or placebo to cognitive behavior therapy in treatment refractory depression: A preliminary trial

ment of depression. However, a meta-analytic review of several short-term psychotherapies for depression sug- gests that a minimum of 13 sessions may be required in order to approach what might be termed maximum ben- efit [31]. In addition, although lithium augmentation can be efficacious within 48 hours of its administration [4] delayed responses (up to 8 weeks) have also been fre- quently observed [3]. Therefore, longer durations of both lithium and quetiapine/CBT treatments might have resulted in a greater number of patients responding. It may also have revealed more improvement in the pla- cebo/CBT group. In this same light, the present study used a flexible dose schedule of quetiapine that was in part based upon patient input. In contrast to the standard anti- depressant drugs, a recommended 'effective' quetiapine dose was simply not available. Therefore, although our average dose approximated that found to be efficacious as an adjunct to SSRI treatment in non-bipolar depression [13] it was much lower than the mono therapy fixed- doses used to treat bipolar depression [12]. Higher doses may have resulted in a greater response. Indeed, these methodological considerations represent one of this study's main limitations.
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Topotecan in the treatment of relapsed small cell lung cancer

Topotecan in the treatment of relapsed small cell lung cancer

Abstract: Small cell lung cancer (SCLC) represents about 15% to 20% of all lung cancers. Chemotherapy is the cornerstone of the treatment, cisplatin–etoposide combination being the most used combination as fi rst-line therapy. Despite high initial chemosensitivity, most SCLC patients will experience relapse sooner or later. Unfortunately, second-line chemotherapy does not result in a high response rate like fi rst-line therapy, most patients having developed wide chemoresistance. This chemoresistance is far more important in refractory patients, ie, those who never responded to fi rst-line therapy or who relapsed within 3 months after the end of chemotherapy, than in sensitive patients, ie, those who relapse more than 3 months after the end of chemotherapy. Topotecan, a topoisomerase I inhibitor, is the most studied drug in this second-line setting and has proved its effi cacy as a single agent and in combination. A phase III trial comparing oral topotecan to best supportive care (BSC) in relapsed SCLC demonstrated a signifi cant survival benefi t as well as a better quality of life. Although the usual schedule is 1.5 mg/m 2 , days 1–5
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Experiences in the treatment of refractory chylothorax associated with lymphoproliferative disorders

Experiences in the treatment of refractory chylothorax associated with lymphoproliferative disorders

Teng et al. [2] described the treatment of malignant chylothorax in a 20-year study of 18 patients (1991– 2011); in 11 of them malignant chylothorax was caused by a lymphoproliferative disease (61%) and in 7 of them by a solid tumor (39%). Indolent lymphomas occurred more often (7 follicular lymphomas, 1 mantle cell lymphoma, 1 lymphoplasmacytic lymphoma) than ag- gressive lymphomas (1 diffuse large B-cell lymphoma, 1 lymphoblastic lymphoma). In our cohort of 10 patients with lymphoproliferative diseases observed for a period of 9 years (2005–2014), indolent lymphoproliferative disorders (5 follicular lymphomas, 4 chronic lymphocytic leukemia/small lymphocytic lymphomas) were also more frequent than aggressive lymphomas (1 non-Hodgkin peripheral T-cell lymphoma not otherwise specified). Compared to Teng et al., our experience also implies that the main factor of the treatment of malignant chylothorax is whether anticancer therapy is effective. Chylothorax cleared in most patients (80%) only after reaching response of the hemato-oncological disease which had caused thoracic duct damage. In the cohort presented by Teng et al. chylothorax cleared simultan- eously with establishing the complete remission of lym- phoproliferation in 6 out of 11 patients (55%).
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Should Levetiracetam or Imepitoin Be Used in Preference as Second line Treatment in Pharmacoresistent Epileptic Cats?

Should Levetiracetam or Imepitoin Be Used in Preference as Second line Treatment in Pharmacoresistent Epileptic Cats?

Intervention details: Studies were grouped based on the antiepileptic drugs evaluated and the overall quality of evidence. Details of the drugs doses, treatment period, pre and post-treatment seizure frequency, and 95% confidence interval of the successfully treated study population were provided.

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Treatment of refractory complex partial seizures: role of vigabatrin

Treatment of refractory complex partial seizures: role of vigabatrin

Several studies have evaluated vigabatrin as monotherapy, compared with carbamazepine (CBZ). The results suggest that VGB is the less effective, but better tolerated, of the 2 drugs. An open-label, randomized controlled study evaluated the efficacy, safety and cognitive effects of initial VGB monotherapy compared to initial CBZ monotherapy in patients with newly diagnosed epilepsy. A total of 100 patients, aged 15 to 64 years, with partial seizures and/or generalized tonic-clonic seizures were randomized to receive either VGB (mean dose 50 mg/kg), or CBZ (titrated to plasma concentrations of 35 µ mol/L) for 1 year. The primary outcome measure was the proportion of patients continuing successful treatment, and was 60% for both drugs, but this number reflects a broad definition of treatment success, which included “acceptable seizure control” in addition to seizure freedom. It is debatable whether the definition of acceptable seizure control (1 to 4 partial seizures and no more than 1 generalized seizure during a treatment period) is appropriate for patients with newly diagnosed epilepsy. Seizure freedom rates significantly differed between the groups: 52% for the CBZ group, and 32% for the VGB group. Although VGB had to be discontinued in some patients due to lack of efficacy, none discontinued due to adverse effects. In contrast, 24% of the CBZ group discontinued treatment due to adverse effects, primarily rash. 31
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Tavistock Adult Depression Study (TADS): a randomised controlled trial of psychoanalytic psychotherapy for treatment resistant/treatment refractory forms of depression

Tavistock Adult Depression Study (TADS): a randomised controlled trial of psychoanalytic psychotherapy for treatment resistant/treatment refractory forms of depression

In relation to the diagnosis of depressive and other com- mon mental disorders, we do not yet know how to carve nature at the joints. If our study were to meet its pri- mary requirement of ecological validity, the sample selected had to involve the fewest possible assumptions. We therefore defined the sample operationally, and included participants with co-morbid Axis I and II disor- ders as well as problems with physical health. Inevitably, this leads to a heterogeneous sample that includes many unknown variations capable of affecting both outcome and the interpretation of findings. Although PPD has the advantage as a treatment of being adaptable to each individual’ s psychopathology, we still expect a large amount of residual variation in responsiveness amongst different patients. The treatment under test will help some participants more than others, and these variations may cancel each other out [116]. In this context, exam- ining mean outcomes, for example, will be insufficient, and while modelling trajectories of outcomes using mixed-effects growth curves allows for differential treat- ment responses to be investigated, this is only possible when the critical moderators involved first have been identified and then measured. In the absence of predic- tions derived from well-founded theories of pathology, this is a hit or miss way of proceeding. The poor per- formance of outcome research in answering the question
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Vol 31, No 10 (2018)

Vol 31, No 10 (2018)

Magnesium sulphate - There is a large experience with magnesium sulphate infusion in the treatment of seizures of eclampsia. Besides hypomagnesemia, there are only iso- lated case reports of its successful use in SRSE. However, its administration is relatively harmless and only contraindi- cated in severe kidney failure (creatinine clearance below 30 ml/min), acute myocardial infarction and cardiac arrhyth- mias. In the reported cases, an initial dose of 4 g followed by a continuous infusion at a rate of 2 – 6 g/h aiming for plasma levels of 3.5 mmol/L were used. 27

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Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report

Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report

stay up longer, and work harder than his classmates. After approximately 3 weeks of intentionally staying up late and sleeping only 4 hours, he developed significant depressive symptoms that continued for more than 2 months. At the onset of this depressive episode, he was evaluated and treated by a psychiatrist, and had trials of citalopram, sertraline, methylphenidate, risperidone, aripiprazole, quetiapine, and lithium during the depressive episode for 12 months. However, these antidepressants and mood stabilizers had little effect on his depressive symptoms. The patient was subsequently referred for a course of rTMS. He received bilateral dorsal medial prefrontal cortex rTMS treatment at 10 Hz, 1,500 pulses per session 32 delivered as an acceler-
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Treating refractory depression in Parkinson’s disease: a meta analysis of transcranial magnetic stimulation

Treating refractory depression in Parkinson’s disease: a meta analysis of transcranial magnetic stimulation

most commonly targeted when treating depression in the non-Parkinson’s population [23, 24, 26]. An open study by Epstein and colleagues directly sought to exam- ine the treatment’s effects in an inpatient setting [23]. The study yielded improvement at post-treatment visits (3 days-post) as well as at 3–6 week follow-up. Our re- sults echoed these findings, showing an extremely notable relationship with high significance between treatment and improved HAM-D and BDI scores (Tables 2 and 3). In a sham-controlled trial, Fregni et al. compare treatment of depression with medication to treatment with magnetic stimulation [24]. The authors found that treatment with rTMS is equally as effective as fluoxetine in treating depression and in most cases better tolerated. In both self-report and clinician- determined measures, very large effect sizes with high significance were found for the medication and stimula- tion groups, showing equally notable effects on depres- sion (Tables 2 and 3). Similarly, Pal and colleagues use a randomized, double-blind, placebo-controlled study to evaluate rTMS to the left DLPFC. In both short term and long term follow-up evaluations (MADRS and BDI), patients reported significant improvement in depressive symptoms. Interestingly, long term follow-ups (at 30 days) yield a larger significant improvement in de- pression scores than the immediate (1 day-post) follow- up. Although effect size could not be evaluated due to insufficient data, the authors provide evidence that pa- tients with PD who experience mild to moderate depres- sion may respond favorable to rTMS.
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Original Article Clinical observation of pulsed radiofrequency in treatment of knee osteoarthritis

Original Article Clinical observation of pulsed radiofrequency in treatment of knee osteoarthritis

ated with pro-inflammatory cytokines (such as local P substance and cytokines) and the occur- rence of osteoarthritis is closely related to car- tilage destruction and inflammation of sub- chondral bone and synovitis; the inflammatory factors secreted in the process are the key mediators that relate to pathophysiology of osteoarthritis, especially IL-1, TNF-α and MMP- 3, they are the key cytokines that control the degeneration of articular cartilage matrix and become the main targets in therapy [18-20]. Other cytokines such as IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor, and IL-8 are also likely to be the targets of OA therapy. There is study showed that pulsed radiofrequency might achieve the purpose of analgesia by two ways [3]: First, by inhibiting the local excitatory C- fiber to affect synaptic transmission, which can block the pathway of pain. This could explain the immediate analgesic effect of the RF, and we found that the pain in patients with severe knee osteoarthritis can be significantly relieved immediately after treatment. Second: the effect on immune response by inhibiting the release of immune cells and pro-inflamma- tory cytokines (interleukin-1β, IL-6, etc.). By regulating these cytokines, pulsed RF stimu- lates a greater level of cascade reaction-stop amplification of inflammatory reaction and avoid vicious circles, which as a mechanism, has a better possibility in the application in big joint, such as the treatment of knee joint cavity in this study. It can explain the mechanisms of long-term pain mitigation after using pulsed RF. The results of this randomized control study were consistent with the results of the retro- spective study of Karaman [5] and further con- firmed the efficacy of pulsed radiofrequency in the treatment of knee osteoarthritis. The next step for us is to explore the optimal time of treatment and the possible mechanisms by experimental studies.
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Management of Peptic Ulcer Bleeding Refractory to Endoscopic Treatment

Management of Peptic Ulcer Bleeding Refractory to Endoscopic Treatment

Despite the retrospective nature of this study, the results show that the management of PUB refractory to en- doscopic treatment is a difficult endeavor with controversial results. The absence of a 24-hour radiology service led by experienced radiologists represents a challenge for many institutions and may have affected the results of the present study. A well-coordinated multidisciplinary team is clearly required for the successful management of this life-threatening condition. Although some studies suggest TAE is a viable alternative to emergency sur- gery and may even be used as the first-line approach, some factors affecting the success rates require further in- vestigation, such as the lower incidence of rebleeding after surgery in patients with type Ia PUB.
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Successful Tocilizumab Treatment in a Child With Refractory Takayasu Arteritis

Successful Tocilizumab Treatment in a Child With Refractory Takayasu Arteritis

Takayasu arteritis (TA) in the child remains a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always safe or ef fi cacious. The complex formed by interleukin- 6 (IL-6) and soluble IL-6 receptor appears to play a pivotal role in the pathogenesis of TA. We describe a favorable response to the anti-IL-6 receptor antibody tocilizumab (TCZ) in a child with aggressive and refractory TA including an assessment of the proin fl ammatory cyto- kine pro fi le. A 3-year-old girl with TA consisting of thickening of the aortic arch wall, severe obstruction of the supra-aortic branches, and complete occlusion of both common carotid arteries failed to respond to corticosteroids, methotrexate, tumor necrosis factor a blockade, cyclophosphamide, and mycophenolate mofetil, and 3 years later, the disease remained active with severe manifestations (brain ischemia). The patient underwent percutaneous angioplasty, although signi fi cant restenosis was soon documented. After a severe relapse, the patient started TCZ infusions (8 mg/kg for 2 weeks), and a rapid clinical remission was observed, associated with a drastic reduction of in- fl ammatory markers and IL-6 levels. Corticosteroids were withdrawn, the patient ’ s weight and height improved, and bone mineral density values returned to normal. Two years later, TCZ infusions were ex- tended, with no signi fi cant side effects. Cerebral ischemia resolved, and recanalization of the previously occluded supra-aortic branches was performed. Pediatrics 2012;130:e1720 – e1724
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Pharmacologic treatment of depression in the elderly

Pharmacologic treatment of depression in the elderly

Main message The goal of treatment should be remission of symptoms. Improvement of symptoms can be monitored by identifying patient goals or by use of a clinical tool such as the Patient Health Questionnaire–9. Treatment should be considered in 3 phases: an acute treatment phase to achieve remission of symptoms, a continuation phase to prevent recurrence of the same episode of illness (relapse), and a maintenance (prophylaxis) phase to prevent future episodes (recurrence). Initial dosing should be half of the usual adult starting dose and be titrated regularly until the patient responds, until the maximum dose is reached, or until side effects limit further increases. Common side effects of medications include falls, nausea, dizziness, headaches, and, less commonly, hyponatremia and QT interval changes. Strategies for switching or augmenting antidepressants are discussed. Older patients should be treated for at least a year from when clinical improvement is noted, and those with recurrent depression or severe symptoms should continue treatment indefinitely. Treatment of specific situations such as severe depression or depression with psychosis is discussed, including the use of electroconvulsive therapy. Criteria for referral to geriatric psychiatry are provided; however, many family physicians do not have easy access to this resource or to other nonpharmacologic clinical strategies.
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Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

Patients who remained in chronic phase at the time of progression appeared to do better with second generation TKIs rather than allogeneic stem cell transplant. In a mul- tivariable analysis however, second-line therapy was not identifi ed as an independent prognostic factor for survival possibly due to the limited follow-up and the multiple, poorly characterized reasons why some patients were referred for transplantation and others not. This retrospective analysis in combination with the results of the dasatinib study in chronic phase mentioned earlier lends support to the notion that some patients in chronic phase may do well with dasatinib therapy alone. Additionally, this study supports the inferences from the phase 2 studies that patients with more advanced disease have relatively poor outcomes with dasatinib alone and that stem cell transplantation should be considered. However, this study does not provide insight into whether patients who respond to dasatinib benefi t from transplantation as compared to continued treatment with dasatinib.
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Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma

Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma

Abstract: Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy.The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6–12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the median duration of response was 6.9 months. At lower dose (25 mg/week), the overall response rate was 41%, median overall survival was 14 months, and time to progression was 6 months. In another trial, 162 patients were randomly assigned to receive temsirolimus at 2 different doses (175 mg/week for 3 weeks, then 75 mg or 25 mg/week) or a treatment chosen by the investigator among the most frequently adopted single agents for treatment of relapsed MCL. Patients treated with 175/75 mg of temsirolimus had significantly higher response rates and longer progression-free survival than those treated with investigator’s choice therapy. These data support the use of mTOR inhibitors for the treatment of MCL, probably in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors.
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New perspectives for the treatment of depression

New perspectives for the treatment of depression

Major depressive disorder is one of the most common psychiatric diseases. Initial reports related to antidepressant efficiency were clouded with the recent studies showing low remission rates in depressed patients in the long term. Therefore, new approaches are needed to develop new treatments. One approach is to redefine symptom patterns and explain the neurobiology of each pattern. Anhedonia is well known symptom of depression but its neurobiology is redefined recently. In this text, anhedonia and its relation with a antidepressant, agomelatin was discussed.
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Review of the use of Topiramate for treatment of psychiatric disorders

Review of the use of Topiramate for treatment of psychiatric disorders

topiramate treated subjects was 5.9 kg compared to 1.2 kg in the placebo group. Median topiramate dose was 212 mg/day (range 50–600). Twenty-six patients discontin- ued. Nine patients (topiramate = 6) because adverse events with paraesthesias and headache as the most com- mon side effects. Topiramate was associated with a signif- icant change in diastolic blood pressure at the last visit compared with placebo among the intent to treat group. There was no significant difference between groups in mean change for the fasting metabolic measurements of insulin, glucose, LDL cholesterol, triglycerides and total cholesterol. Hoopes et al., [97] enrolled 69 patients with DSM-IV bulimia nervosa in a randomised, double blind, placebo controlled trial. Sixty-four patients (33 in the pla- cebo group vs. 31 in the topiramate group) were included in the intent to treat analysis. The primary efficacy meas- ure, mean weekly number of binge and/or purge days, decreased 44.8% from baseline in the topiramate group versus 10.7% in the placebo group (p = 0.004). This was confirmed by significant reduction in scores on the Bulimic Intensity Scale, 37% for topiramate vs. 14% for placebo. The trial lasted for 10 weeks and the median dose was 100 mg/day (range 25–400). Topiramate, adminis- tered in monotherapy, was commenced at 25 mg/day for the first week. The dose was titrated by 25–50 mg incre- ments per week to a maximum of 400 mg/day. Response supervened within 10 weeks. Only 3 patients discontin- ued from the trial (2 placebo, 1 topiramate) due to adverse events (topiramate: nausea). Shapira et al. [98] studied 13 female patients with binge eating disorder in a naturalistic, open label, add-on study. All the patients had co-morbid diagnoses. Treatment was begun at 25 mg/day and subsequently increased by 25–50 mg/week according to response and side effects to 1400 mg/day, given in divided doses. Response and side effects were valuated ret- rospectively as recalled by patients
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Temsirolimus in the treatment of relapsed or refractory mantle cell lymphoma

Temsirolimus in the treatment of relapsed or refractory mantle cell lymphoma

Abstract: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of lymphoma associated with a poor prognosis. Chemotherapy is the mainstay of frontline treatment for patients with this disease. Despite high response rates to combination chemotherapy regimens, the majority of patients relapse within a few years of treatment. Therefore, finding efficacious treatments for relapsed or refractory disease has become a growing area of clinical research. The mammalian target of rapamycin (mTOR) is responsible for integrating cell signals from growth factors, hormones, and nutrients and communicating energy status. Scientific research on aberrant molecular pathways in cancer has revealed that several proteins along the mTOR pathway may be upregulated in this and other types of lymphoma. Temsirolimus is the first mTOR inhibitor that has shown clinical efficacy in treating MCL that has relapsed after frontline treatments.
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