90 research outputs found
From the breast to the upper jaw: A rare case of metastatic breast cancer
Breast cancer is the commonest malignancy in women globally. Metastasesof advanced breast carcinoma to bones, lungs and liver are well known but spread to maxillary bone presenting as maxillary sinus and palatal swelling is rare. We present a case of advanced breast carcinoma in a female Nigerian with clinical, radiological and histopathological features of lung and right maxillary bone metastases. To the best of our knowledge, this is the first reported case of metastatic breast cancer to the lungs and maxilla in Nigeria. The debilitating sequelae of advanced untreated breast carcinoma in a resource limited setting with suboptimal comprehensive cancer care are highlighted.
Keywords: Breast cancer; orofacial metastasis; resource limited setting, Nigeri
Kolaviron was protective against sodium azide (NaN 3 )induced oxidative stress in the prefrontal cortex
Kolaviron is a phytochemical isolated from
Garcina kola (G. kola);
a common oral masticatory agent in
Nigeria (West Africa). It is
a
bioflavonoid used - as an antivi-
ral, anti-inflammatory and antioxidant - in relieving the symp-
toms of several diseases and infections. In this study we have
evaluated the neuroprotective and regenerative effect of
kolaviron in neurons of the prefrontal cortex (Pfc) before or
after exposure to sodium azide (NaN
3
) induced oxidative
stress. Separate groups of animals were treated as follows;
kolaviron (200 mg/Kg) for 21 days; kolaviron (200 mg/Kg
for21days)followedbyNaN
3
treatment (20 mg/Kg for
5days);NaN
3
treatment (20 mg/Kg for 5 days) followed by
kolaviron (200 mg/Kg for 21 days); 1 ml of corn-oil (21 days-
vehicle); NaN
3
treatment (20 mg/Kg for 5 days). Exploratory
activity associated with Pfc function was assessed in the open
field test (OFT) following which the microscopic anatomy of
the prefrontal cortex was examined in histology
(Haematoxylin and Eosin) and antigen retrieval Immunohis-
tochemistry to show astroglia activation (GFAP), neuronal
metabolism (NSE), cytoskeleton (NF) and cell cycle dysreg-
ulation (p53). Subsequently, we quantified the level of
Glucose-6-phosphate dehydrogenase (G6PDH) and lactate
dehydrogenase (LDH) in the brain tissue homogenate as a
measure of stress-related glucose metabolism. Kolaviron
(Kv) and Kolaviron/NaN
3
treatment caused no prominent
change in astroglia density and size while NaN
3
and NaN
3
/
Kv induced astroglia activation and scar formation
(astrogliosis) in the Pfc when compared with the control. Sim-
ilarly, Kolaviron and Kv/NaN
3
did not alter NSE expression
(glucose metabolism) while NaN
3
and NaN
3
/Kv treatment
increased cortical NSE expression; thus indicating stress
related metabolism. Further studies on enzymes of glu-
cose metabolism (G6PDH and LDH) showed that NaN
3
increased LDH while kolaviron reduced LDH in the
brain tissue homogenate
(P<0.001).
In addition
kolaviron treatment before
(P<0.001)
or after
(
P
<0.05) NaN
3
treatment also reduced LDH expression;
thus supporting its role in suppression of oxidative
stress. Interestingly, NF deposition increased in the Pfc
after kolaviron treatment while Kv/NaN
3
showed no sig-
nificant change in NF when compared with the control.
In furtherance, NaN
3
and NaN
3
/Kv caused a decrease in
NF deposition (degeneration). Ultimately, the protective
effect of KV administered prior to NaN
3
treatment was
confirmed through p53 expression; which was similar to
the control. However, NaN
3
and NaN
3
/Kv caused an
increase in p53 expression in the Pfc neurons (cell cycle
dysregulation). We conclude that kolaviron is not neu-
rotoxic when used at 200 mg/Kg BW. Furthermore,
200 mg/Kg of kolaviron administered prior to NaN
3
treatment (Kv/NaN
3
) was neuroprotective when com-
pared with Kolaviron administered after NaN
3
treatment
(NaN
3
/Kv). Some of the observed effects of kolaviron
administered before NaN
3
treatment includes reduction
of astroglia activation, absence of astroglia scars, anti-
oxidation (reduced NSE and LDH), prevention of neu-
rofilament loss and cell cycle regulatio
Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma
Purpose: Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients >= 65 years in ZUMA-7. Patients and Methods: Patients with LBCL refractory to or relapsed = 65 years were random-ized to axi-cel and SOC, respectively. Median EFS was greater with axi-cel versus SOC (21.5 vs. 2.5 months; median follow-up: 24.3 months; HR, 0.276; descriptive P = 3 adverse events occurred in 94% of axi-cel and 82% of SOC patients. No grade 5 cytokine release syndrome or neurologic events occurred. In the quality-of-life analysis, the mean change in PRO scores from baseline at days 100 and 150 favored axi-cel for EORTC QLQ-C30 Global Health, Physical Functioning, and EQ-5D-5L visual analog scale (descriptive P = 65 and = 65 years with R/R LBCL
Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma
ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 Ă 106 CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade â€2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population
Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.
Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia
The advent of chimeric antigen receptor (CAR) T-cell therapy has led to dramatic remission rates in multiple relapsed/refractory hematologic malignancies. While CAR T-cell therapy has been particularly successful as a treatment for B-cell malignancies, effectively treating acute myeloid leukemia (AML) with CARs has posed a larger challenge. AML not only creates an immunosuppressive tumor microenvironment that dampens CAR T-cell responses, but it also lacks many unique tumor-associated antigens, making leukemic-specific targeting difficult. One advantage of CAR T-cell therapy compared to alternative treatment options is the ability to provide prolonged antigen-specific immune effector and surveillance functions. Since many AML CAR targets under investigation including CD33, CD117, and CD123 are also expressed on hematopoietic stem cells, CAR T-cell therapy can lead to severe and potentially lethal myeloablation. Novel strategies to combat these issues include creation of bispecific CARs, CAR T-cell âsafety switchesâ, TCR-like CARs, NK CARs, and universal CARs, but all vary in their ability to provide a sustained remission, and consolidation with an allogeneic hematopoietic cell transplantation (allo-HCT) will be necessary in most cases This review highlights the delicate balance between effectively eliminating AML blasts and leukemic stem cells, while preserving the ability for bone marrow to regenerate. The impact of CAR therapy on treatment landscape of AML and changing scope of allo-HCT is discussed. Continued advances in AML CAR therapy would be of great benefit to a disease that still has high morbidity and mortality
Racial differences in the pattern of hematologic toxicity in the treatment of colorectal cancer.
Role of bridging therapy during chimeric antigen receptor T cell therapy
Abstract Chimeric antigen receptor (CAR) Tâcell therapy has been approved for use in several relapsed/refractory hematologic malignancies and has significantly improved outcomes for these diseases. A number of different CAR T products are now being used in clinical practice and have demonstrated excellent outcomes to those in clinical trials. However, increased realâworld use of CAR T therapy has uncovered a number of barriers that can lead to significant delays in treatment. As a result, bridging therapy has become a widely used tool to stabilize or debulk disease between leukapheresis and CAR T cell administration. Here we review the available data regarding bridging therapy, with a focus on patient selection, choice of therapy, timing of therapy, and potential pitfalls
Chimeric antigen receptor Tâcell therapy: Challenges and framework of outpatient administration
Abstract Adoptive cellular therapy has made a landmark change within the treatment paradigm of several hematologic malignancies, and novel cellular therapy products, such as chimeric antigen receptor Tâcell therapy (CART), have demonstrated impressive efficacy and produced durable responses. However, the CART treatment process is associated with significant toxicities, healthcare resource utilization, and financial burden. Most of these therapies have been administered in the inpatient setting due to their toxicity profile. Improved toxicity management strategies and a better understanding of cellular therapy processes are now established. Therefore, efforts to transition CART to the outpatient setting are warranted with the potential to translate into enhanced patient quality of life and cost savings. A successful launch of outpatient CART requires several components including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Telemedicine should be incorporated for closer monitoring. Additionally, clear criteria for admission upon clinical decompensation, a pathway for prompt inpatient transition, and clear toxicity management guidelines should be implemented. Effective education about cellular therapy and toxicity management is imperative, especially for the Emergency Department and Intensive Care Unit teams. Here, we have outlined the various logistical and clinical considerations required for the care of CART patients, which will aid centers to establish an outpatient CART program
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