Bispecific antibodies (bsAb) that target two independent epitopes or antigens have been extensively explored in translational and clinical studies since they were first developed in the 1960s. Many bsAbs are being tested in clinical trials for treating a variety of diseases, mostly cancer. Here, we provide an overview of various types of bsAbs in clinical studies and discuss their targets, safety profiles, and efficacy. We also highlight the current challenges, potential solutions, and future directions of bsAb development for cancer treatment.
The posterior inferior cerebellar artery (PICA), with its unique anatomical complexity, is of great clinical importance and involved in many diseases including aneurysm, ischemic stroke, neurovascular compression syndrome (NVCS), arteriovenous malformation (AVM), and brain tumor. However, a comprehensive systematic review of the importance of the PICA is currently lacking. In this study, we perform a literature review of PICA by searching all the associated papers in the PUBMED database hoping to provide a better understanding of the artery. The PICA has tortuous and variable course and territory, divided into 5 segments. Various aneurysms involving PICA were not uncommon, of which the treatment is challenging. The PICA infarct typically manifests lateral medullary syndrome (LMS) and is more likely to cause mass effects. The PICA frequently compresses the medulla and the cranial nerves resulting in various neurovascular compression syndromes (NVCS). Arteriovenous malformation (AVM) fed by PICA are associated with aneurysm and dissection which have high risk of rupture and worse outcome. PICA injured by head trauma can cause fatal SAH. VA terminating in PICA probably cause Bow hunter's syndrome (BHS). The PICA supplies many brain tumors and can be used in intracerebellar chemotherapy. The PICA can be exposed and injured during surgeries especially in telovelar approach, and it also plays an important role in bypass surgeries, hinting the surgical importance of PICA. In conclusion, PICA is very important in clinical practice.
Background:
Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain (AL) amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac AL amyloidosis.
Methods:
This was a multicenter, open-label randomized controlled trial. Patients with Mayo 2004 stage II-III AL amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression or organ progression (heart, kidney or liver). Hematologic progression was defined based on substantial increase in free light chain. Increase in either N-terminal pro B-type natriuretic peptide or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated using a Cox regression model.
Results:
140 patients underwent randomization, with 70 in each group. The median age was 61 (range, 33-78) years with a male: female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32/70 (45.7%) of patients in the doxycycline group and 30/70 (42.9%) of patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio 0.97, 95% CI, 0.59-1.60,
p
=0.91). Cardiac progression occurred in 29/70 (41.4%) of patients in the doxycycline group and 26/70 (37.1%) of patients in the control group. The death rates for both groups by the end of follow-up was the same, 25/70 (35.7%). There were no significant differences observed for either cardiac PFS (hazard ratio 0.91, 95% CI, 0.54-1.55,
p
=0.74) or overall survival (hazard ratio 1.04, 95% CI, 0.60-1.81,
p
=0.89).
Conclusions:
Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac AL amyloidosis.
Clinical Trial Registration:
URL: https://clinicaltrials.gov Unique Identifier: NCT03401372.
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