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International Journal of Hyperthermia :... 2024Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment...
PURPOSE
Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms.
METHODS
We developed a dedicated MW-HT heating setup, created an and MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors.
RESULTS
Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups.
CONCLUSION
MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.
Topics: Humans; Male; Animals; Mice; Prostatic Neoplasms, Castration-Resistant; PC-3 Cells; Reactive Oxygen Species; Microwaves; Tumor Suppressor Protein p53; Hyperthermia, Induced; Prostatic Neoplasms; DNA Repair; Apoptosis; Oxidative Stress; Hyperthermia; Adenocarcinoma; DNA; Cell Line, Tumor; Cell Proliferation
PubMed: 38583875
DOI: 10.1080/02656736.2024.2335201 -
Poultry Science Jun 2024The aim of this study was to investigate the effects of prolonged exposure to varying levels of music or noise on the behavioral, physiological, and immune responses of...
The aim of this study was to investigate the effects of prolonged exposure to varying levels of music or noise on the behavioral, physiological, and immune responses of pullets following their transfer to an egg-laying facility. A total of 240 one-day-old Hy-Line Brown pullets were randomly assigned to five groups: 0 dB sound stimulation, low-decibel music (65-75 dB), high-decibel music (85-95 dB), low-decibel noise (65-75 dB), and high-decibel noise (85-95 dB) stimuli. Pullets received music or noise stimuli 10 h per d from 1-day-old to 16-wk-old and were then transferred to the egg-laying facility. The results indicated that feeding and drinking behaviors significantly decreased (P < 0.05), whereas feather pecking, aggression, and preening behaviors significantly increased (P < 0.05) in the pullets after transfer. Pullets also had higher serum cortisol (COR) levels (P < 0.05), whereas immunoglobulin Y (IgY), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-1β (IL-1β), interleukin-2 (IL-2) and interleukin-6 (IL-6) levels significantly increased (P < 0.05). Low-decibel sound stimuli increased aggressive behavior and decreased pecking behavior (P < 0.05). High-decibel sound stimuli decreased feather pecking, cage pecking, aggression, and sham dustbathing behaviors (P < 0.05). In addition, a low-decibel sound stimulus decreased the serum COR content, and increased the serum IL-6 level in the transferred pullets. A high-decibel sound stimulus also induced shorter tonic immobility (TI) durations in pullets on d 7 after transport stress. Meanwhile, high-decibel sound stimulus decreased the serum IL-6 and TNF-α levels of pullets. In conclusion, the transfer has detrimental effects on the pullets. Long-term sound stimulation effectively mitigated the negative impact of transportation stress on pullets. Among them, the high-decibel sound stimulus showed more promise in relieving transport stress.
Topics: Animals; Chickens; Hydrocortisone; Female; Random Allocation; Behavior, Animal; Noise; Housing, Animal; Animal Husbandry; Stress, Physiological
PubMed: 38579543
DOI: 10.1016/j.psj.2024.103689 -
JAMA Network Open Apr 2024Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).
OBJECTIVE
To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.
DESIGN, SETTING, AND PARTICIPANTS
This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.
INTERVENTION
This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI.
MAIN OUTCOME AND MEASURES
The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis.
RESULTS
Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678).
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02912312.
Topics: Female; Humans; Middle Aged; Breast; Breast Neoplasms; Mammaplasty; Mastectomy; Neoplasm Recurrence, Local; Adult; Aged
PubMed: 38578640
DOI: 10.1001/jamanetworkopen.2024.5217 -
Frontiers in Oncology 2024
PubMed: 38571498
DOI: 10.3389/fonc.2024.1366261 -
Frontiers in Oncology 2024Chondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a...
INTRODUCTION
Chondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a literature review was performed to examine the efficacy of PT and photon radiotherapy for skull base chondrosarcoma.
METHODS
The meta-analysis was conducted using 21 articles published from 1990 to 2022.
RESULTS
After PT, the 3- and 5-year overall survival (OS) rates were 94.1% (95% confidence interval [CI]: 91.0-96.2%) and 93.9% (95% CI: 90.6-96.1%), respectively, and the 3- and 5-year local control rates were 95.4% (95% CI: 92.0-97.4%) and 90.1% (95% CI: 76.8-96.0%), respectively. Meta-regression analysis revealed a significant association of PT with a superior 5-year OS rate compared to three-dimensional conformal radiotherapy (p < 0.001). In the studies used in the meta-analysis, the major adverse event of grade 2 or higher was temporal lobe necrosis (incidence 1-18%, median 7%).
CONCLUSION
PT for skull base chondrosarcoma had a good outcome and may be a valuable option among radiotherapy modalities. However, high-dose postoperative irradiation of skull base chondrosarcoma can cause adverse events such as temporal lobe necrosis.
PubMed: 38567162
DOI: 10.3389/fonc.2024.1380716 -
Laboratory Animal Research Apr 2024Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the...
BACKGROUND
Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified. Currently, the only effective treatment for RAD is rehabilitation. Additionally, there are few available animal models of RAD, necessitating the development of new models to establish and evaluate RAD treatments. We hypothesize that radiation-induced neck muscle fibrosis could be one of the causes of RAD due to impairment of laryngeal elevation. Therefore, in this study, we focused on the changes in inflammation and fibrosis of the strap muscles (Sternohyoid, Sternothyroid, and Thyrohyoid muscles) after a single-dose irradiation. This research aims to provide a reference animal model for future studies on RAD.
RESULTS
Compared to control mice, those treated with 72-Gy, but not 24-Gy, irradiation had significantly increased tumor necrosis factor-α (TNF-α) (p < 0.01) and α-smooth muscle actin (αSMA) (p < 0.05) expression at 10 days and significantly increased expression levels of motif chemokine ligand-2 (CCL2), α-SMA, tumor growth factor-β1 (TGF-β1), type1 collagen, and interleukin-1β (IL-1β) (p < 0.05) in the muscles at 1 month by real-time PCR analysis. The results of immunohistochemistry showed that the deposition of type 1 collagen gradually increased in extracellular space after radiation exposure, and the positive area was significantly increased at 3 months compared to non-irradiated control.
CONCLUSIONS
A single dose of 72-Gy irradiation induced significant inflammation and fibrosis in the strap muscles of mice at 1 month, with immunohistochemical changes becoming evident at 3 months. This cervical irradiation-induced fibrosis model holds potential for establishing an animal model for RAD in future studies.
LEVEL OF EVIDENCE
N/A.
PubMed: 38561867
DOI: 10.1186/s42826-024-00199-2 -
Cureus Feb 2024Thermal, electrical, chemical, or electromagnetic radiation can cause painful wounds or burns. Spilling hot liquids onto the skin can also cause these kinds of... (Review)
Review
Thermal, electrical, chemical, or electromagnetic radiation can cause painful wounds or burns. Spilling hot liquids onto the skin can also cause these kinds of injuries. The two biggest factors contributing to burn injuries in the elderly are smoking and exposure to open flames, while scalding is the primary cause of burn damage in children. Newborns and the elderly make up the majority of burn casualties. In India, there are estimated to be 6-7 million burn cases per year. The high incidence is attributed to the population's illiteracy, poverty, and lack of awareness of safety. The problem is made much worse by the fact that basic and secondary healthcare levels do not provide systematic burn care. Coagulation necrosis is caused by denaturing proteins due to heat from burns. Platelets clump together, arteries narrow, and partly perfused tissue (called the stasis zone) may spread out around the wound. In the stasis zone, tissue is hyperemic and inflammatory. When the skin's natural barrier is breached, microorganisms can enter the body and cause poor temperature regulation, fluid loss, and invasion. Intravascular volume loss is typically worsened by injured or edematous tissues. Significant heat loss may occur from the wounded dermis' lack of thermoregulation, particularly in exposed wounds. The severity determines the different treatments. Serious burns require considerable care, while lesser burns just require cleaning and painkillers. Just-partially thickened burns must be cleansed with soap and water before being clothed. For full-thickness burns, surgery, including skin grafting, is frequently required. Extensive intravenous fluid doses are often required to treat serious burns resulting from tissue edema and capillary fluid leakage.
PubMed: 38544618
DOI: 10.7759/cureus.54915 -
Medicina (Kaunas, Lithuania) Mar 2024: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with...
: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. : We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. : A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively ( = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively ( = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively ( = 0.56 and = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) ( = 0.98) and 5yOS 100% vs. 93.3% ( = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. : eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.
Topics: Male; Humans; Young Adult; Adult; Middle Aged; Female; Hodgkin Disease; Prednisone; Retrospective Studies; Cyclophosphamide; Vincristine; Bleomycin; Doxorubicin; Adrenal Cortex Hormones; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 38541156
DOI: 10.3390/medicina60030430 -
Radiotherapy and Oncology : Journal of... Jun 2024This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with... (Meta-Analysis)
Meta-Analysis Review
This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with three-dimensional conformal RT (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). TLN is a serious late complication that can adversely affect the quality of life of NPC patients. Understanding the relationship between dosimetric parameters and TLN can guide treatment planning and minimize radiation-related complications. A comprehensive search identified relevant studies published up to July 2023. Studies reporting on dosimetric parameters and TLN in NPC patients undergoing 3D-CRT, IMRT, and VMAT were included. TLN incidence, follow-up duration, and correlation with dosimetric parameters of the temporal lobe were analyzed. The review included 30 studies with median follow-up durations ranging from 28 to 110 months. The crude incidence of TLN varied from 2.3 % to 47.3 % and the average crude incidence of TLN is approximately 14 %. Dmax and D1cc emerged as potential predictors of TLN in 3D-CRT and IMRT-treated NPC patients. Threshold values of >72 Gy for Dmax and >62 Gy for D1cc were associated with increased TLN risk. However, other factors should also be considered, including host characteristics, tumor-specific features and therapeutic factors. In conclusion, this systematic review highlights the significance of dosimetric parameters, particularly Dmax and D1cc, in predicting TLN risk in NPC patients undergoing 3D-CRT, IMRT, and VMAT. The findings provide valuable insights that can help in developing optimal treatment planning strategies and contribute to the development of clinical guidelines in this field.
Topics: Humans; Nasopharyngeal Carcinoma; Temporal Lobe; Necrosis; Radiation Injuries; Nasopharyngeal Neoplasms; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Radiotherapy, Conformal
PubMed: 38537680
DOI: 10.1016/j.radonc.2024.110258 -
Cureus Feb 2024Penile calciphylaxis is a rare presentation of calcific uremic arteriolopathy and can be a life-threatening condition usually seen in patients with end-stage renal...
Penile calciphylaxis is a rare presentation of calcific uremic arteriolopathy and can be a life-threatening condition usually seen in patients with end-stage renal failure with hemodialysis. The clear etiopathogenesis of calciphylaxis is not fully understood, but it is postulated to be characterized by the accumulation of calcium in the microvessels of adipose tissue and skin, which leads to ischemia and necrosis, causing painful ulcerations, and could potentially be complicated by sepsis and mortality. End-stage renal disease (ESRD) is one of the major risk factors for penile calciphylaxis. In this report, we describe a case of a 53-year-old Hispanic male patient with ESRD and diabetes on hemodialysis, who presented with a five-day history of acute, severe, burning, non-radiating pain to the head of his penis associated with black discoloration. He was diagnosed with penile calciphylaxis and received a combination of conservative and surgical interventions, resulting in a highly positive outcome marked by complete healing of the scar without any reported complications.
PubMed: 38529436
DOI: 10.7759/cureus.54824