Acute Side Effects Research Articles

Alleviating rheumatoid arthritis with a photo-pharmacotherapeutic glycan-integrated nanogel complex for advanced percutaneous delivery

The prospective of percutaneous drug delivery (PDD) mechanisms to address the limitations of oral and injectable treatment for rheumatoid arthritis (RA) is increasing. These limitations encompass inadequate compliance among patients and acute gastrointestinal side effects. However, the skin’s intrinsic layer can frequently hinder the percutaneous dispersion of RA medications, thus mitigating the efficiency of drug delivery. To circumvent this constraint, we developed a strontium ranelate (SrR)-loaded alginate (ALG) phototherapeutic hydrogel to assess its effectiveness in combating RA. Our studies revealed that this SrR-loaded ALG hydrogel incorporating photoelectrically responsive molybdenum disulfide nanoflowers (MoS2 NFs) and photothermally responsive polypyrrole nanoparticles (Ppy NPs) to form ALG@SrR-MoS2 NFs-Ppy NPs demonstrated substantial mechanical strength, potentially enabling delivery of hydrophilic therapeutic agents into the skin and significantly impeding the progression of RA. Comprehensive biochemical, histological, behavioral, and radiographic analyses in an animal model of zymosan-induced RA demonstrated that the application of these phototherapeutic ALG@SrR-MoS2 NFs-Ppy NPs effectively reduced inflammation, increased the presence of heat shock proteins, regulatory cluster of differentiation M2 macrophages, and alleviated joint degeneration associated with RA. As demonstrated by our findings, treating RA and possibly other autoimmune disorders with this phototherapeutic hydrogel system offers a distinctive, highly compliant, and therapeutically efficient method.

Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition

Osteosarcoma (OS) is the most severe bone tumor in children. A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin. These drugs cause acute and chronic side effects, such as infections, thrombocytopenia, neutropenia, DNA damage, and inflammation. Therefore, to identify new therapeutic strategies, effective and with a safety profile, is necessary. The Hedgehog (Hh) signaling pathway involved in tumorigenesis is active in OS. Hh components Patched receptor 1 (PTCH1), Smoothened (SMO), and glioma-associated oncogene homolog transcription factors (GLI1 and GLI2) are overexpressed in OS cell lines and patient samples. Curcumin (CUR)—with antioxidant and anti-cancer properties—downregulates Hh components in cancer, inhibiting progression. This study investigates CUR effects on the MG-63 OS cell line, alone and combined with MTX, to propose a novel therapeutic approach. Our study suggests CUR as a novel therapeutic agent in OS, particularly when combined with MTX. Targeting the Hh signaling pathway, CUR and MTX showed significant pro-apoptotic effects, increasing the BAX/Bcl-2 ratio and total apoptotic cell percentage. They reduced the expression of Hh pathway components (PTCH1, SMO, GLI1, and GLI2), inhibiting OS cell proliferation, survival, and invasion. CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

Vomiting despite adherence to guidelines: Suboptimal control of vomiting in pediatric cancer patients.

Vomiting is a common and distressing acute side effect of chemotherapy, negatively impacting quality of life, nutritional status, and the ability of patients to tolerate further treatment. Standardized guidelines have been developed to improve control of nausea and vomiting. We aimed to determine the benefit of adherence to clinical practice guidelines (CPGs) on complete control of acute chemotherapy-induced vomiting in newly diagnosed pediatric patients with cancer. An electronic dashboard of pediatric patients newly diagnosed with cancer at Phoenix Children's Hospital between August 2019 and January 2021 and receiving their first cycle of chemotherapy was utilized to monitor chemotherapy regimen, antiemetic medications, and vomiting episodes. Blocks were classified as guideline-inconsistent, guideline-consistent, or guideline-consistent PLUS if additional prophylactic antiemetic medications were utilized. We identified patients with complete control of vomiting, defined as no vomiting and no additional antiemetics needed. Among 136 patients, 29% received guideline-inconsistent care, 37% received guideline-consistent care, and 34% received guideline-consistent PLUS care. Overall, 48% of patients achieved complete control of vomiting. Older patients (p<0.0001) and those receiving higher emetogenicity chemotherapy (p=0.0003) were more likely to receive guideline-consistent or guideline-consistent PLUS therapy. With guideline-consistent and -consistent PLUS grouped together, the diagnosis was also associated with improved adherence to CPGs (p=0.022). Multivariate analysis showed that patients more likely to receive guideline-consistent prophylaxis were of older age (OR 1.11, p=0.016) and solid tumor patients (OR 5.59, p=0.028). Despite high rates of CPG adherence, complete control of vomiting remains suboptimal, which highlights the need for novel and/or risk-adapted therapies.

Treatment preferences of patients with muscle invasive bladder cancer: A discrete choice experiment

AbstractBackgroundWhen faced with treatment options, patients are asked to participate in decision‐making. We sought to determine which treatment aspects matter most for individuals treated for muscle invasive bladder cancer (MIBC), with an aim to improve understanding of patient preferences and what trade‐offs patients are willing to accept. Our study consisted of a discrete choice experiment (DCE): a type of questionnaire used to elicit preferences in the absence of real‐world choice.MethodsThe DCE had five attributives, each with three levels. Participants were asked to complete a questionnaire in which they were asked to choose between two hypothetical MIBC treatments. The data were analysed using a conditional logit model, and preferences for, and trade‐offs between, attributes were estimated.ResultsWe recruited patients with MIBC who had either already completed, were undergoing or had yet to commence radical treatment for MIBC (n = 60). Participants indicated a strong preference for treatments that increased their life expectancy (p = &lt;0.001), had a lower risk of long‐term complications (p = &lt;0.001) and less changes to their body image (p = &lt;0.001). Changes to sexual wellbeing (p = 0.09) or an increase in acute side effects (p = 0.99) did not influence preferences. Patients were willing to accept treatments with higher risk of long‐term complications to improve their life expectancy or body image.ConclusionWhen deciding on the type of treatment, increased life expectancy is the most important consideration for people with MIBC. The risk of long‐term complications and changes to overall body image as a result of treatment are also important. Our study also highlighted that patients are willing to accept a higher risk of long‐term complications to improve other treatment outcomes. Understanding patient preferences is important for shared decision‐making, which has an impact on quality of care for people living with MIBC.

Patients-Reported Outcomes of Acute Side Effects During Head and Neck Cancer Radiotherapy: A Cross-Sectional Study at Andalas University Hospital Padang

Background: Head and neck cancer is a malignancy originating from the upper aerodigestive tract. Head and neck cancer patients undergoing radiotherapy using brachytherapy, 2DRT, 3CDRT, and IMRT techniques. Patients undergoing radiotherapy will experience several acute side effects consisting of mucositis, dysphagia, xerostomia, and dermatitis. This is influenced by the technique and dose given. This study aims to grade and time the acute side effects of radiotherapy for head and neck cancer at the Andalas University Hospital Padang. Methods: A quantitative descriptive method with a cross-sectional approach is used. Secondary data with a total sample of 88 patients. This research uses medical record data and is analyzed using statistical analysis methods. Results: This study found that the most head and neck cancer patients who underwent radiotherapy were male 57 (64.8%) patients, nasopharyngeal subsite 41 (46.6%) patients with non-keratinizing nasopharyngeal carcinoma 32 (36.4%) patients. The most common radiotherapy technique for head and neck cancer was IMRT in 58 (65.9%) patients with a dose of 61-70 Gy in 78 (88.6%) patients and the most common stage was IV A in 51 (58%) patients. Patients did not undergo chemotherapy treatment in 51 (58%) and surgery in 69 (78.4%). Body mass index (BMI) before radiotherapy was normal in 74 (84.1%) patients and after radiotherapy became underweight in 57 (64.8%) patients resulting in weight loss 1 kg in 83 (94.3%) patients. The highest grade of radiotherapy side effects was grade 1 which consisted of mucositis 84 (95.5%), dysphagia 83 (94.3%), xerostomia 78 (88.6%), and dermatitis 78 (88.6%) patients. The most frequent timing of mucositis side effects occurred in the 3rd week in 40 (45%) patients, dysphagia in the 3rd week in 41 (47%) patients, xerostomia in the 3rd week in 33 (38%) patients, and dermatitis at week 6 in 24 (27%) patients. Conclusions: Patients with head and neck cancer who undergo radiotherapy from week 1 to week 7 will experience side effects, including mucositis, dysphagia, xerostomia, and dermatitis. The average side effect appears in the 3rd week with grade 1.

Analysis of Residual Tetraacetylethylenediamine Levels according to Rinsing Time of Denture Cleanser

Objective: Tetraacetylethylenediamine (TAED), a denture cleanser was reported to have a risk of acute side effects at high concentrations. This study evaluated residual TAED from denture cleansers after rinsing for different durations. Methods: The rinsing times of denture cleansers were investigated. Specimens made with the denture base-resin were immersed in a denture cleanser and rinsed with running water. The experimental groups were divided based on the rinsing time; G1 was rinsed for 10 s, G2 for 20 s, G3 for 30 s, and G4 for 60 s. No rinsing was performed in the control group. After the elution of TAED from the samples, quantification was performed using high-performance liquid chromatography and mass spectrometry. Results: Seven denture cleansers were investigated; however, the specific rinsing time was not confirmed. Conversely, the control group had a significantly higher amount of TAED (315.4±104.7 ㎍/L), whereas the other groups with &gt; 10 s rinsing time showed significantly decreased residual TAED. Conclusions: To prevent the potential risks of TAED, users should rinse their dentures thoroughly for ≥ 10 s after using a denture cleanser.

Recent discoveries of oral substances’ effects on osteoporosis treatment - novel markers and pathways

The search for optimal osteoporosis treatments continues, as the medications currently used in clinical therapy carry a risk of rare but acute side effects. New knowledge about etiopathogenetic pathways and osteoporosis biomarkers enabled the exact examination of various oral substances, often previously recognised for their positive impact on bone mass growth. A cross-section of novel reports from this year on the applications of many orally administered substances is presented. Diet, gut microbiota aspect, functional food, diabetes drug – empagliflozin and a variety of substances known from Chinese traditional medicine are now characterized in the context of the possible mechanism of treating or preventing osteoporosis. The progress of bone mass density and quality-regulating pathways recognition led to the finding of multiple orally administered substances with favorable mediation properties. The precise diagnosis of the substances' working mechanisms approves their potential use in new formulations of clinical treatments. Presently only used in diet supplementation, the orally administrated antiosteoporotic substances are potential core ingredients of modernized medications, provided their presumptive adverse effects are ruled out.

1591: Acute side-effects from proton beam therapy for head & neck cancer: A 1-year, single centre review

1591: Acute side-effects from proton beam therapy for head & neck cancer: A 1-year, single centre review

CT-based radiomics for predicting breast cancer radiotherapy side effects

Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume.

Prevention and management of radiotherapy-related toxicities in gynecological malignancies. Position paper on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology)

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

SEOM-GG clinical guidelines for the management of germ-cell testicular cancer (2023)

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors.

Photobiomodulation therapy: Ushering in a new era in personalized supportive cancer care

Abstract The human body can utilize light for a broad range of pathophysiological responses, such as circadian rhythm, Vitamin D metabolism, and vision, among others. The therapeutic use of light has spanned many ancient health practices. Recent advances in using low-dose light therapy, termed photobiomodulation (PBM), have made tremendous progress in unravelling precise biological mechanisms and clinical dosimetry, enabling this treatment modality’s clinical safety and effectiveness. The evidence for PBM has received its strongest endorsement via recent systematic reviews and meta-analyses recommending its routine use to address various acute and chronic side effects associated with cancer treatment. Carefully done studies have noted unequivocal evidence demonstrating its effectiveness in managing oral mucositis in patients undergoing radiotherapy for head and neck cancer, chemotherapy, or hematopoietic stem cell transplantation. This brief narrative review will explore the therapeutic benefits of PBM therapy, supported by recent research findings, to provide a comprehensive understanding of its potential in clinical settings. Additionally, the review will highlight our current understanding of molecular mechanisms underlying PBM and the importance of novel harmonized dosing that enables its optimal clinical implementation and utilization.

The spectrum of late radiation sequelae in head and neck cancer

ABSTRACT Introduction: Concurrent Chemoradiation is the standard of care in the treatment of unresectable locally advanced head and neck cancer. Some of the acute side effects seen after or alongside the head and neck radiotherapy include dermatitis, mucositis, xerostomia, dysphagia and swallowing dysfunction. Evolving data demonstrate that acute toxicities may persist long-term and develop into late effects. In addition, late effects may manifest months or years after completion of therapy, persisting for years or even lifelong, far longer than previously believed. When severe, late effects may profoundly affect function and quality of life. The present study was conducted to analyze the spectrum of late radiation toxicities in head and neck cancer patients treated with radical external beam radiation therapy and to determine its prevalence and severity. Materials and Methods: This prospective observational study was conducted in the Department of Radiotherapy, Christian Medical College and Hospital, Ludhiana. In all patients with a histopathological diagnosis of head and neck carcinoma who have received radical radiation therapy alone or definitive chemoradiation as part of cancer-directed therapy. Results: Salivary gland toxicity was the most common toxicity encountered in head and neck cancer survivors resulting in dysphagia followed by dental caries, subcutaneous late effects and dysphagia. As expected, the spectrum of side effects correlated with the primary site, stage of disease and ECOG performance status. Conclusion: Technological advancement in radiation planning and equipment has resulted in a reduction in the most feared side effects of radiation which has led to improvement in the quality of life of the survivors. As no technology can entirely protect normal tissues from irradiation, utmost care should be taken to minimize the radiation dose received by normal tissues by following preventive and supportive measures.

Incidence and severity of acute radiation induced toxicities among breast cancer patients treated with adjuvant radiotherapy at a major cancer treatment center in Ghana

BackgroundAdjuvant radiotherapy after mastectomy or breast conserving surgery (BCS) is the standard of care for majority of patients with breast cancer. This is however associated with mucosal and epidermal toxicity of organs at risk (OARs). Breast cancer patients are exposed to a plethora of wrong perceptions, misinformation and myths concerning the usefulness and adverse effects of radiotherapy. There is paucity of literature on the incidence and severity of radiation-induced acute toxicities experienced by patients with breast cancer in Ghana. AimTo assess the occurrence and severity of four main acute radiation-induced toxicities among female breast cancer patients treated with external beam radiotherapy at a major cancer treatment centre in Ghana. MethodsData on the occurrence of acute toxicities among patients was collected from patients' medical records, through a semi-structured questionnaire and via weekly clinical assessments. The Common Terminology Criteria for Adverse Events (CTCAE) grading scale (version 4.0) was used to grade the severity of these toxicities. Descriptive and inferential statistics using an independent two-sampled t-test (two-tailed), one-way analysis of variance (ANOVA), Pearson's Chi-square and Fisher's exact tests were performed. ResultsDermatitis, fatigue, pharyngitis, and breast (chest) pain were the radiation toxicities found among the breast cancer patients undergoing treatment on the two machines. The mean predominant radiation doses associated with the onset of dermatitis, fatigue, pharyngitis, and chest pain in the breast cancer patients were 22.32 Gy, 22.48 Gy, 13.59 Gy, and 19.27 Gy respectively for treatment with a statistically significant (p = 0.0173). Radiation dermatitis was the most dominant acute radiation toxicity recorded, and its incidence and severity. The range of Fisher's p-values (0.689–0.999) between the acute radiation toxicities with both machines revealed no statistical significance. ConclusionRadiation dermatitis was the dominant acute toxicity, both in incidence and severity for patients treated. There was no statistical significance in the incidence and severity of acute radiation side effects.

The Value and Safety of Adjuvant Radiation Therapy After Radical Cystectomy in Locally Advanced Urothelial Bladder Cancer: A Controlled Randomized Study

BackgroundAdjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue. Patients and methodsOne hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; a hundred and twenty-two were randomized to receive adjuvant radiotherapy (ART) 50 Gy/25 fractions, 4 weeks’ post-cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and sixty in the CY arm. Twenty-four ART and 30 CY patients received Neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neo-bladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity-modulated radiotherapy (IMRT) with daily verification cone-beam CT (CBCT). The median follow-up was 42.7 months. ResultsThe 3-year adjusted Locoregional relapse-free survival (LRFS) rate was higher in the ART arm, measuring 81% (95%CI: 69-94) compared to 71% (95% CI: 60-80) (p=0.0457). ART significantly improved the locoregional relapse-free rate in the cystectomy bed and the pelvic side wall (p= 0.016 and 0.001, respectively). The overall survival, event-free, and distant metastasis-free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the two groups. ConclusionsAdjuvant radiotherapy is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the LRFS but had insignificant improvement on the overall survival. ART did not affect the distant metastasis-free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer.

Neoadjuvant chemotherapy with bevacizumab for locally advanced vulvar cancer

ObjectivesExternal beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects....

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

Therapeutic Doses of Antioxidants Inhibit the Growth and Enhance the Effects Chemotherapy and Radiation Therapy on Cancer Cells by Blocking the Uptake and Metabolism of Glucose and Glutamine

Chemotherapy and radiation therapy have produced increased 5-year survival rate in majority of cancers; however, acute side-effects during treatment and late adverse effects after these therapies remain a major concern of oncologists. To improve further 5-year survival rate and reduce acute and late adverse effects of therapies, a new non-toxic biological approach is needed. Experimental data for such an approach was available for over 25 years. For example, therapeutic doses of antioxidants inhibit the growth of cancer cells and enhances the growth-inhibitory effects of chemotherapeutic agents and x-irradiation on cancer cells but not on normal cells. These exciting observations failed to draw any attention from oncologists, because mechanistic data on therapeutic doses was not available until now. The mechanistic data on preventive doses of antioxidants suggested that they scavenge free radicals. Since one of the mechanisms of action of chemotherapy and radiation therapy on cancer cells is mediated by free radicals, oncologists fear that supplementation with antioxidants may reduce the effectiveness of cancer therapies by neutralizing free radicals. Cancer cells require glucose and glutamine for their survival and proliferation. This review briefly describes the effects of therapeutic doses of antioxidants alone and in combination with chemotherapy and radiation therapy on the growth of neoplastic cells and normal cells. It also presents evidence to show that such doses of antioxidants reduce the uptake and metabolism of glucose and glutamine in cancer cells. We propose that therapeutic doses of multiple antioxidants can selectively kill cancer cells and enhance the growth-inhibitory effects of therapeutic agents on cancer cells without affecting normal cells by inhibiting the uptake and metabolism of glucose and glutamine.

The Use of Anabolic Steroids by Bodybuilders in the State of Sergipe, Brazil.

Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive-analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex (p = 0.492), age (p = 0.460), family income (p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved (p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% (n = 20), irritability at 32.1% (n = 19), alopecia (hair loss), and nervousness at 23.7% (n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% (n = 9), liver disease at 28.0% (n = 7), and cancer (non-specific) at 8.0% (n = 2). We concluded that, regardless of the athletes' socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes.

Radiotherapy for Canine Apocrine Gland Anal Sac Adenocarcinoma: Survival Outcomes and Side Effects of a Palliative Treatment Protocol of 20 Gy in Five Consecutive Fractions.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198-569) and 628 days (95% CI 579-676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282-391 days), and 402 days (95% CI 286-517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.