• Effect of Electrical Capacitance-Based Therapy on the Viability of U87 and T98-G Glioblastoma Cell Lines.
    1 week ago
    AIM: To examine the selective cytotoxic effects of Electro-Capacitive Cancer Therapy (ECCT) on human glioblastoma (GBM) cell lines (U87-MG and T98-G) and to evaluate its impact on normal epithelial cells. MATERIAL and METHODS: U87-MG and T98-G glioblastoma cells, along with Beas-2B normal epithelial cells, were exposed to ECCT at 100 kHz frequency and 20 V for 24 hours. Cell viability was determined using the MTT assay, while morphological changes were assessed through phase-contrast microscopy. Statistical analyses were conducted using one-way ANOVA and Student's t-test, with statistical significance defined as p < 0.05. RESULTS: ECCT exposure caused a time-dependent reduction in the viability of both GBM cell lines. U87-MG cells showed significant inhibition at all exposure durations, whereas T98-G cells exhibited a marked decrease only after 24 hours (p < 0.0001). In contrast, Beas-2B cells maintained their morphology and viability, suggesting that ECCT selectively targets malignant cells while sparing normal epithelial cells. CONCLUSION: ECCT significantly inhibits glioblastoma cell proliferation without adversely affecting normal cells, highlighting its promise as a non-invasive adjunctive treatment option for GBM. Further preclinical and clinical studies are warranted to clarify its underlying mechanisms, optimize exposure parameters, and determine its potential integration into multimodal glioblastoma therapy.
    Cancer
    Care/Management
  • The Role of Exosomal Biomarkers in the Monitoring of Bioactivation and Metabolite Clearance of Chemotherapeutics in Cancer Patients.
    1 week ago
    Bioactivation and clearance of anticancer agents are crucial factors in the efficacy and toxicity of anticancer drugs. Exosomes are membrane-bound vesicles secreted by tumor cells and the tumor microenvironment. These vesicles contain drug-metabolizing enzymes, transporters, and RNA. Exosomes can be non-invasively collected from the blood. This article has been prepared by combining the evidence of the role of exosomal cytochrome P450 isoforms, such as cytochrome P450 family 2 subfamily C member 19, cytochrome P450 family 2 subfamily D member 6, and cytochrome P450 family 3 subfamily A member 5, in the oxidation of anticancer drugs in the first phase of drug metabolism. Exosomal UDP-glucuronosyltransferase 1A1 has been found to help in the conjugation of anticancer drugs in the second phase of drug metabolism. Exosomal ATP-binding cassette transporters, P-glycoprotein, multidrug resistance-associated protein 1, and breast cancer resistance protein have been found to act as intercellular conveyors of drug efflux capacity. These transporters can modulate the efficacy of chemotherapy. Exosomal microRNAs, such as microRNA-21, microRNA-155, and microRNA-1246, have been found to modulate apoptosis, DNA repair, metabolic adaptation, and chemotherapy resistance through the PI3K/AKT pathway, EZH2/STAT3 pathway, and PDCD4 pathway. Long non-coding RNAs, such as UCA1 and HOXA antisense RNA, can reprogram the chromatin structure. These long non-coding RNAs can suppress tumor suppressor genes, thus leading to chemotherapy resistance. Bioinformatics pipelines have been designed to bridge the gap between exosomal RNA and protein levels in the profile of dynamic metabolic states. The challenges in the field of exosomal therapy drug monitoring have been discussed in the article. The article has recommended the use of artificial intelligence in the integration of omics with microfluidic technology for the improvement of exosomal therapy drug monitoring.
    Cancer
    Care/Management
  • Jujuboside a Improves Polycystic Ovary Syndrome Through SIRT3-Mediated PINK1/Parkin-Dependent Mitochondrial Autophagy in Ovarian Granulosa Cells.
    1 week ago
    Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its treatment remains a significant challenge. This study investigated the mechanism of Jujuboside A (JuA) in the treatment of PCOS through mitophagy. Granulosa cells (GCs) were collected from follicular fluid derived from PCOS women. The effects of JuA on PCOS were determined by measuring body weight, ovarian weight, estrous cycle, glucose level, insulin tolerance, and ovarian morphology in dehydroepiandrosterone-induced mice. SIRT3 expression levels were quantified in GCs, KGN cells, and mouse ovaries. The effects of JuA on SIRT3-related oxidative stress and mitochondrial damage were investigated in KGN cells and mice. Transmission electron microscopy was used to observe mitochondrial damage and mitophagy in GCs. The expression of mitophagy-related proteins (PINK1 and Parkin) was analyzed. JuA significantly improved body weight, estrous cycle, ovarian morphology, glucose tolerance, and insulin resistance, partially restoring ovarian function in PCOS mice. Moreover, JuA significantly activated SIRT3 expression and alleviated SIRT3-related oxidative stress and mitochondrial damage in mouse ovaries, GCs, and KGN cells. Mechanistically, JuA upregulated SIRT3 and inhibited excessive activation of the PINK1/Parkin pathway to reduce mitophagy. These findings demonstrated JuA protected GCs from mitochondrial damage by activating SIRT3 and inhibiting PINK1/Parkin-mediated mitophagy.
    Cancer
    Care/Management
  • The rationale for monitoring both skin and invasive temperatures in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and superficial microwave hyperthermia exceeding 1 cm target depth.
    1 week ago
    Thermoradiotherapy at 40-43 °C is an effective treatment for locoregional recurrent (LRR) breast cancer patients. During hyperthermia temperature monitoring is often limited to skin temperatures, but their predictive value for achieving locoregional tumor control (LRC) remains unclear for tumor depths ≥1cm. This study compared predictive value of skin versus invasive intratarget temperatures.

    We reported earlier the thermal dose-effect relationship in 112 patients with LRR breast cancer treated in 2010-2017 with postoperative re-irradiation (8 × 4 Gy/23 × 2 Gy) and 4-5 weekly hyperthermia sessions with 434 MHz microwave applicators. Bolus cooling enabled semi-superficial target depths (1-4 cm), thermocouple thermometry monitored both skin and intratarget temperatures. The present study analyzes relationships between LRC and average skin and intratarget median temperature T50 and best session with highest median thermal dose CEM43T50 (cumulative equivalent minutes at 43 °C). Pearson correlation coefficient analysis evaluated correlation between intratarget and skin temperature parameters.

    Average median skin and invasive temperatures were T50 = 40.6 °C (Interquartile Range IQR 40.3-40.8) and T50 = 40.7 °C (IQR 40.0-41.3), respectively, without association between skin and intratarget temperatures. Median CEM43T50 for skin and intratarget were 2.8 (IQR 2.0-4.3) and 7.2 min (IQR 3.4-15.9) in the best hyperthermia session, respectively. Twenty-four patients developed infield recurrences; median time-to-recurrence was 3.4 years (IQR 2.7-4.6 years). Univariate and multivariate analysis showed significant association of intratarget temperature parameters with LRC (p = 0.015; p = 0.021, respectively), but not for skin temperature parameters and LRC (p = 0.131; p = 0.215, respectively).

    Temperature monitoring using both skin and invasive intratarget measurements is key for ensuring good quality superficial hyperthermia delivery for tumor depths ≥1cm.
    Cancer
    Care/Management
  • Lip health among maritime workers in the Baixada Santista Port Region - clinical evaluation and development of a protective moisturizer.
    1 week ago
    Fishermen are among the occupational groups with substantial sun exposure and are prone to dehydration, sunburn, photoaging, actinic cheilitis, and oral cancer. The objective of this study was to evaluate the dermatological condition of the lips of fishermen in the Guarujá/Santos port region, investigate whether they use preventive measures to avoid such lesions, and develop a suitable product for lip protection.

    Thirty participants underwent an initial clinical examination and photo-graphic documentation. All 30 participants received the developed lip protector, which contained UV filters and moisturizing agents. At re-evaluation one month later, 17 participants returned, corresponding to a loss to follow-up of 43.40%.

    All fishermen were male, with a minimum age of 23 and a maximum age of 74. When asked about lip balm use, only 1 of the 30 participants reported using it. At follow-up, among the 17 participants, only 1 reported using the provided lip balm and reapplying it during the day; this use was described as "sporadic."

    The findings highlight the need for educational strategies to promote lip protection and prevent potentially malignant lesions among outdoor workers exposed to ultraviolet radiation.
    Cancer
    Care/Management
  • Osteosarcoma of the Jaws in Latin America: A Retrospective Multicenter Series of 119 Cases.
    1 week ago
    Epidemiological and survival data on osteosarcoma of the jaws (OSJ) in Latin America remain scarce. We characterized the clinicopathological, radiographic, treatment-related, and survival features of OSJ in Latin America.

    This multicenter case series involved 22 institutions from Brazil, Chile, Argentina, Colombia, Venezuela, Uruguay, and Mexico. Demographic, clinical, radiographic, histopathological, treatment, and survival data were analyzed using descriptive and inferential statistical methods. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models.

    A total of 119 OSJ cases were included. The median age was 33 years, with a female predominance (58%), and the mandible was the most commonly affected site (68.9%). A mixed radiographic appearance predominated and was frequently accompanied by cortical perforation and a sunburst periosteal reaction. Histologically, the osteoblastic subtype accounted for 63.5% of cases. Surgical resection was the main treatment modality (71.2%). Increasing age (p = 0.034) and multimodal or nonsurgical management (p = 0.023) were independently associated with poorer survival. The estimated overall survival rates were 67.5% at 12 months and 37.5% at 60 months.

    Data corroborate previous literature and demonstrate that OSJ in Latin America predominantly affects adults and exhibits aggressive patterns. Surgical management remains central to improving survival whenever it is technically feasible.
    Cancer
    Care/Management
  • Poly(ADP-ribose) Polymerase Inhibitor Talazoparib Inhibits DNA Damage Repair in Breast Cancer Cell Lines With or Without BRCA1/2 Mutation.
    1 week ago
    Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. Although PARP inhibitor sensitivity has traditionally been attributed to synthetic lethality in tumors with BRCA1/2 mutations or homologous recombination repair deficiency, emerging evidence indicates that clinical and preclinical activity may extend to selected tumors beyond those harboring germline BRCA1/2 mutations. This study investigated the mechanism underlying talazoparib efficacy in both BRCA1/2-mutant and BRCA1/2 wild-type breast cancer cells.

    Twenty-one breast cancer cell lines, including both BRCA-1/2-mutant and wild-type cells, were treated with talazoparib, and the effects of the treatment on cell proliferation, cell cycle progression, DNA damage accumulation, and apoptosis were evaluated.

    Talazoparib demonstrated antiproliferative effects in BRCA1/2-mutant and wild-type cells in a long-term culture system, as assessed by colony formation assays. Accumulation of single-stranded and double-stranded DNA damage was observed in talazoparib-sensitive cell lines, as indicated by phosphorylated RPA and γ-H2AX, respectively. This was accompanied by G2/M arrest and subsequent apoptosis, as evidenced by cleaved caspase-3 expression and Annexin V staining. Abnormal mitotic nuclei were observed in talazoparib-sensitive cell lines, which also exhibited potent and sustained PARP1 trapping on chromatin.

    Talazoparib exerts anti-tumor effects in BRCA1/2-mutant and wild-type breast cancer cells by promoting the formation of abnormal mitotic nuclei and inducing apoptosis in sensitive cells. Our findings support the potential therapeutic application of talazoparib beyond its current indications for BRCA1/2-mutant tumors.
    Cancer
    Care/Management
  • Real-World Patient-Reported Outcome Comparing Antibody-Drug Conjugates and Conventional Chemotherapy in Metastatic Breast Cancer.
    1 week ago
    Antibody-drug conjugates (ADCs) have transformed second-line metastatic breast cancer (MBC) therapy, yet their multidimensional quality-of-life impact versus conventional intravenous chemotherapy in real-world practice, particularly on lifestyle and caregiver burden, remains poorly characterized.

    This prospective cohort enrolled 122 consecutive patients with MBC starting second-line therapy: 51 received ADCs and 71 conventional intravenous chemotherapy, allocated by tumor biology and clinical factors. The DAMA (Digital Antibody drug conjugate Modulator in breAst cancer) framework collected electronic patient-reported outcome measures (ePROMs) on anthropometric, lifestyle, symptom, psychosocial, and caregiver-burden domains at baseline, 3 and 6 months, analyzed with linear mixed-effects models.

    At baseline, measured lifestyle, symptom, psychosocial and caregiver variables were broadly similar between cohorts, although treatment-related characteristics differed. At 3 months, ADC patients had greater mean weight loss (-3.1 vs - 1.2 kg), a larger decline in weekly physical activity (-41 vs - 22 minutes/week), higher stress and caregiver burden, but lower pain scores (3.7 vs 5.3). By 6 months, several differences attenuated. In pooled descriptive analyses, weekly physical activity showed little association with pain (r = 0.03, p = 0.56), stress (r = -0.12, p = 0.03), anxiety (r = -0.02, p = 0.73), caregiver emotional wellbeing (r = 0.00, p = 0.97), or sleep duration (r = 0.04, p = 0.47).

    In this prospective real-world cohort, ADC and conventional chemotherapy cohorts showed different longitudinal patterns of patient- and caregiver-reported burden. Because treatment allocation was biology- and clinically driven, these findings are exploratory and should not be interpreted as causal treatment effects. Systematic ePROM collection within the DAMA framework was feasible and may support identification of supportive-care needs.
    Cancer
    Care/Management
  • Reduced venesection requirement as a clue to occult colorectal cancer in hereditary haemochromatosis.
    1 week ago
    Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. We report a case of CRC in a man in his late 70s with hereditary haemochromatosis (HH) who historically required venesection two to three times per year to maintain target ferritin levels. Despite the absence of gastrointestinal symptoms or anaemia, his requirement for maintenance venesection unexpectedly ceased and ferritin levels remained low without treatment. Two faecal immunochemical tests were negative. Colonoscopy subsequently revealed an adenocarcinoma in the caecum. Chronic occult blood loss from the tumour likely counterbalanced the increased intestinal iron absorption characteristic of HH. This case highlights that an unexplained reduction in venesection requirements in HH may represent an early marker of occult gastrointestinal blood loss and should prompt consideration of further investigation.
    Cancer
    Care/Management
  • Unexpected parasternal musculature during skin-sparing mastectomy and microvascular breast reconstruction.
    1 week ago
    The sternalis muscle is an uncommon anatomical variant of the anterior thoracic wall. Although regarded as functionally insignificant, its presence may influence diagnostic interpretation, surgical dissection and reconstructive planning in breast surgery. We report bilateral sternalis muscles discovered during bilateral skin-sparing mastectomy and immediate autologous reconstruction in a woman in her late 40s. The sternalis muscles were identified intraoperatively, following which retrospective review of preoperative imaging confirmed their presence. Recognition of this variant aided orientation and safe exposure of the internal mammary vessels during reconstruction. Awareness of the sternalis muscle can prevent imaging misinterpretation, avoid intraoperative confusion and optimise reconstructive outcomes.
    Cancer
    Care/Management