-
Colloids and Surfaces. B, Biointerfaces Jun 2024In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis...
In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis during cancer treatment. Even though continuous progress in research offers more and more tools to combat cancer, we still lack a proper arsenal of therapeutics. Especially in tumors with close to no targeting options, like triple-negative breast cancer, early detection is often the main difference between successful and failed therapy. When such tumors are detected too late, they may have already produced plenty of CTCs, likely causing metastasis, which is the primary reason for tumor-associated deaths. Detecting those CTCs early on could substantially impact therapy outcomes and the 5-year survival rate. In our study, we developed and evaluated a reliable and affordable CTC screening method based on flow cytometry and 5-aminolevulinic acid (5-ALA) staining. We successfully established a circulation model for 5-ALA and CTCs research and demonstrated that the method can detect an average of 11 ± 3.3 CTCs out of 10,000 peripheral blood mononuclear cells, representing as low as approximately 0.1 % with a reasonable number of false positive events. Additionally, we present initial results on a theranostic approach using 5-ALA converted to protoporphyrin IX. The outcomes of this study might contribute significantly to the further development of CTC detection and the overall detection and treatment of cancer.
PubMed: 38941652
DOI: 10.1016/j.colsurfb.2024.114059 -
Pharmaceutics Jun 2024Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to...
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.
Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.
PubMed: 38931936
DOI: 10.3390/pharmaceutics16060815 -
Journal of Clinical Medicine Jun 2024Glioma surgery has been remarkably enhanced in the past 2 decades, with improved safety and limited but improved life expectations. The fluorescence-guided resection of...
Glioma surgery has been remarkably enhanced in the past 2 decades, with improved safety and limited but improved life expectations. The fluorescence-guided resection of high-grade gliomas (HGGs) plays a central role in this sense, allowing a greater extent of resection (EOR). The introduction of exoscopic-guided surgery may be considered in implementing fluorescence techniques over traditional microscopes. We present the application and the advantages of exoscopic-guided surgery compared to microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGGs. Ten consecutive patients underwent surgery for HGG resection. The surgery was performed via an exoscopic-guided procedure (Olympus ORBEYE) and after the oral administration of Gliolan 5 h before the procedure. During surgery, the procedure shifted to using a microscopic (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different procedures was subjectively measured in different picture samples during the surgery on a 1 to 5 (from minimum to maximum) scale. The brightness of the surgical field and the detailing of the anatomy were also analyzed comparatively. Among the ten patients, the histopathological diagnosis was an high-grade glioma in all cases. In nine cases, it was possible to achieve gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the exoscope group and 3.5 in the microscope group ( < 0.01). The exoscopic-guided surgery adds advantages to traditional fluorescence-guided surgery with 5-aminolevulinic acid. Beyond the important advantage of low cost and the possibility to perform collaborative surgeries, it adds a plain and continuous visualization of the tumor and offers advantages in the surgical field of fluorescence-guided glioma surgery compared to the microscopic-guided one.
PubMed: 38930021
DOI: 10.3390/jcm13123493 -
Cancers Jun 2024(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The...
(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time ( = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.
PubMed: 38927947
DOI: 10.3390/cancers16122242 -
Biomedicines Jun 2024Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell...
Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell and tissue damage that is activated by exposure to visible light. PDT selectively acts on cancer cells, which have an accumulation of photosensitizer superior to that of the normal surrounding tissues. 5-aminolevulinic acid (5-ALA) induces the production of protoporphyrin IX (PpIX), an endogenous photosensitizer activated in PDT. This study aimed to test the effect of a new gel containing 5% / 5-ALA (ALAD-PDT) on human oral CAL-27 and pancreatic CAPAN-2 cancer cell lines. The cell lines were incubated in low concentrations of ALAD-PDT (0.05%, 0.10%, 0.20%, 0.40%, 0.75%, 1.0%) for 4 h or 8 h, and then irradiated for 7 min with 630 nm RED light. The cytotoxic effects of ALAD-PDT were measured using the MTS assay. Apoptosis, cell cycle, and ROS assays were performed using flow cytometry. PpIX accumulation was measured using a spectrofluorometer after 10 min and 24 and 48 h of treatment. The viability was extremely reduced at all concentrations, at 4 h for CAPAN-2 and at 8 h for CAL-27. ALAD-PDT induced marked apoptosis rates in both oral and pancreatic cancer cells. Elevated ROS production and appreciable levels of PpIX were detected in both cell lines. The use of ALA-PDT as a topical or intralesional therapy would permit the use of very low doses to achieve effective results and minimize side effects. ALAD-PDT has the potential to play a significant role in complex oral and pancreatic anticancer therapies.
PubMed: 38927525
DOI: 10.3390/biomedicines12061316 -
Fukushima Journal of Medical Science Jun 20245-Aminolevulinic acid (5-ALA) is orally administered 2-4 hours before surgery to identify tumor location. Hypotension is sometimes observed after 5-ALA administration....
5-Aminolevulinic acid (5-ALA) is orally administered 2-4 hours before surgery to identify tumor location. Hypotension is sometimes observed after 5-ALA administration. Case reoprtWe present a case of a patient with 5-ALA-induced hypotension that resulted in the development of cerebral infarction. An 83-year-old man with a bladder tumor was scheduled for photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) and right radical nephroureterectomy. 5-ALA was orally administered and his ordinary antihypertensive and antianginal agents were also administered an hour after 5-ALA administration. Following this, his blood pressure dropped, and he developed muscle weakness and paralysis in his left upper extremity. Magnetic resonance imaging showed evidence of cerebral infarction. ConclusionsWe cannot conclude definitively that our patient's cerebral infarction was solely caused by 5-ALA-induced hypotension because hypotension under these circumstances is not rare. We consider that additional factors, such as patient-specific doses of antihypertensive and antianginal agents may have played a role in the development of his cerebral infarction.
PubMed: 38925956
DOI: 10.5387/fms.24-00001 -
Photochemistry and Photobiology Jun 2024Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re-populate the tumor milieu due to...
Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re-populate the tumor milieu due to selection following conventional therapies. Here, we show that 5-aminolevulinic acid (ALA) treatment-a pro-fluorophore used for fluorescence-guided cancer surgery-leads to elevated levels of fluorophore conversion in patient-derived GSC cultures, and subsequent red light-activation induces apoptosis in both intrinsically temozolomide chemotherapy-sensitive and -resistant GSC phenotypes. Red light irradiation of ALA-treated cultures also exhibits the ability to target mesenchymal GSCs (Mes-GSCs) with induced temozolomide resistance. Furthermore, sub-lethal light doses restore Mes-GSC sensitivity to temozolomide, abrogating GSC-acquired chemoresistance. These results suggest that ALA is not only useful for fluorescence-guided glioblastoma tumor resection, but that it also facilitates a GSC drug-resistance agnostic, red light-activated modality to mop up the surgical margins and prime subsequent chemotherapy.
PubMed: 38922889
DOI: 10.1111/php.13985 -
Asian Pacific Journal of Cancer... Jun 2024Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor...
OBJECTIVE
Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities.
METHODS
In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient.
RESULTS
Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF.
CONCLUSION
This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.
Topics: Humans; Photochemotherapy; NF-kappa B; Photosensitizing Agents; Aminolevulinic Acid; Female; Cell Proliferation; Breast Neoplasms; Dimethyl Fumarate; Apoptosis; Reactive Oxygen Species; Tumor Cells, Cultured; Cell Line, Tumor
PubMed: 38918667
DOI: 10.31557/APJCP.2024.25.6.2051 -
International Journal of Surgery... Jun 2024Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures...
Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures must delicately balance tumor removal with the preservation of surrounding tissue. Achieving clear margins is particularly challenging in cases like glioblastoma due to the limitations of traditional white light visualization. These limitations often result in incomplete resections, leading to frequent recurrences, or excessive resection that harms vital neural structures, causing iatrogenic nerve damage which can lead to sensory and functional deficits. Current statistics reveal a 90% recurrence rate for malignant gliomas. Similarly, an 8% incidence of iatrogenic nerve trauma contributes to an estimated 25 million cases of peripheral nerve injury globally each year. These figures underscore the urgent need for improved intraoperative techniques for lesion margin and nerve identification and visualization. Recent advances in neurosurgical imaging, such as fluorescence-guided surgery (FGS), have begun to address these challenges. Fluorescent agents used in FGS illuminate target tissues, although not all do so selectively. Despite the promising results of agents such as 5-aminolevulinic acid and indocyanine green, their applications are mainly limited by issues of sensitivity and specificity. Furthermore, these agents do not effectively address the need for precise nerve visualization. Nerve Peptide 41, a novel systemically administered fluorescent nerve-targeted probe, shows promise in filling this gap. This review assesses the major fluorescent imaging modalities in neurosurgery, highlighting each of their benefits, limitations, and potential.
PubMed: 38913424
DOI: 10.1097/JS9.0000000000001847 -
Oncology Letters Aug 2024Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Photodynamic therapy (PDT) is a promising therapeutic method for managing cSCC...
Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma.
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Photodynamic therapy (PDT) is a promising therapeutic method for managing cSCC due to its proven ability to target specific areas over time and its low risk of side effects. PDT may cause tissue damage and vascular shutdown, and may regulate local immunological responses. The present study aimed to investigate and compare the early lymphocyte modifications before and after PDT for SCC. A total of 10 patients with SCC were identified by pathological investigation. Initially, all wounds were treated with 20% aminolevulinic acid (ALA)-PDT as the initial stage in the therapeutic procedure. The wounds were treated by exposing them to red LED light with a wavelength of 635 nm, an energy density of 100 J/cm and an intensity of 80 mW/cm. The tumor tissue was surgically removed 24 h later, and another round of PDT therapy was administered. Immunohistochemistry for CD3 and CD56 was conducted on the wound tissue post-surgery. If the wound showed granulation, necrosis or secretion, debridement was added to the therapy. All patients were monitored for 0.6-1.0 year post-treatment. ALA-PDT combination surgery fully controlled the tumor tissue in all 10 patients. The immunohistochemical analysis of the wound tissues showed that the expression of CD56 increased, while the expression of CD3 was not different after photodynamic therapy. These results also indirectly indicated that the overall count of NK cells in the 10 patients increased, nevertheless, there was no alteration in the T lymphocyte count. In conclusion, the ALA-PDT combination surgical therapy for cSCC demonstrates favorable results. An increase in CD56 expression may be a mechanism for the effective treatment of cSCC with PDT.
PubMed: 38910905
DOI: 10.3892/ol.2024.14505