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Journal of Oral Biosciences Jun 2024This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the...
Regional difference in the distribution of alkaline phosphatase, PHOSPHO1, and calcein labeling in the femoral metaphyseal trabeculae in parathyroid hormone-administered mice.
OBJECTIVES
This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes.
METHODS
Six-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (Sham group) and groups receiving hPTH (1-34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks.
RESULTS
The Sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the Sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions.
CONCLUSIONS
Administration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.
PubMed: 38942193
DOI: 10.1016/j.job.2024.06.007 -
Biochimie Jun 2024Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy...
Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6 expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential. In addition, the knockdown of IGFBP6 leads to impaired lipid metabolism. In this study, we demonstrated that the knockdown of the IGFBP6 gene, a highly selective inhibitor of IGF-II, led to a significant decline in the number of secreted extracellular vesicles (EVs) and altered cholesterol metabolism in MDA-MB-231 cells. Knockdown of IGFBP6 led to a decrease in the essential proteins responsible for the biogenesis of cholesterol LDLR and LSS, which reduced the amount by more than 13 times. In addition, the knockdown of IGFBP6 led to a possible change in the profile of adhesion molecules on the surface of EVs. The expression of L1CAM, IGSF3, EpCAM, CD24, and CD44 decreased, and the expression of EGFR increased. We can conclude that the negative prognostic value of low expression of this gene could be associated with increased activity of IGF2 in tumor-associated fibroblasts due to low secretion of IGFBP6 by tumor cells. In addition, changing the profile of adhesion molecules on the surface of tumor EVs may contribute to the more efficient formation of metastatic niches.
PubMed: 38942135
DOI: 10.1016/j.biochi.2024.06.011 -
Gynecologic Oncology Jun 2024To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
OBJECTIVE
To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
METHODS
A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors.
RESULTS
A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS.
CONCLUSION
PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.
PubMed: 38941964
DOI: 10.1016/j.ygyno.2024.06.010 -
Cardiovascular and Interventional... Jun 2024Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
PURPOSE
Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
MATERIALS AND METHODS
An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS).
RESULTS
Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively.
CONCLUSION
IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.
PubMed: 38943032
DOI: 10.1007/s00270-024-03795-w -
Communications Biology Jun 2024The Mycoplasma Immunoglobulin Binding/Protease (MIB-MIP) system is a candidate 'virulence factor present in multiple pathogenic species of the Mollicutes, including the...
The Mycoplasma Immunoglobulin Binding/Protease (MIB-MIP) system is a candidate 'virulence factor present in multiple pathogenic species of the Mollicutes, including the fast-growing species Mycoplasma feriruminatoris. The MIB-MIP system cleaves the heavy chain of host immunoglobulins, hence affecting antigen-antibody interactions and potentially facilitating immune evasion. In this work, using -omics technologies and 5'RACE, we show that the four copies of the M. feriruminatoris MIB-MIP system have different expression levels and are transcribed as operons controlled by four different promoters. Individual MIB-MIP gene pairs of M. feriruminatoris and other Mollicutes were introduced in an engineered M. feriruminatoris strain devoid of MIB-MIP genes and were tested for their functionality using newly developed oriC-based plasmids. The two proteins are functionally expressed at the surface of M. feriruminatoris, which confirms the possibility to display large membrane-associated proteins in this bacterium. However, functional expression of heterologous MIB-MIP systems introduced in this engineered strain from phylogenetically distant porcine Mollicutes like Mesomycoplasma hyorhinis or Mesomycoplasma hyopneumoniae could not be achieved. Finally, since M. feriruminatoris is a candidate for biomedical applications such as drug delivery, we confirmed its safety in vivo in domestic goats, which are the closest livestock relatives to its native host the Alpine ibex.
Topics: Bacterial Vaccines; Mycoplasma; Animals; Bacterial Proteins; Immunoglobulins; Gene Expression Regulation, Bacterial; Mycoplasma Infections; Goats
PubMed: 38942984
DOI: 10.1038/s42003-024-06497-8 -
Urologic Oncology Jun 2024Similar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical...
INTRODUCTION
Similar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC.
METHODS
We consecutively enrolled 77 patients treated between 2009 and 2022 by radical surgery for UTUC from a secondary and a tertiary referral center. A pathology review of all specimens was performed by 1 independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis was performed to assess the association with clinical characteristics and the Kaplan-Meier estimator to compare outcomes.
RESULTS
Median follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 7/21 (33%) and micropapillary 3/21 variants (14%). Neuroendocrine carcinoma was present in 2 patients. Nested variant was found in 1 patient. Muscle invasive tumor (≥pT2) was present in 30/56 (54%) patients with pure UTUC and in 18/21 (86%) patients with VH (P < 0.05). Presence of carcinoma in situ was seen in 24/56 (43%) patients with pure UTUC and in 16/21 (76%) with VH (P < 0.05). Cumulative 8/56 (14%) with pure UTUC had a nonintravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (P < 0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (P < 0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs. 42% (P 0.28) and 3yr-CSS 77% vs. 50% (P 0.7).
CONCLUSION
Almost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy.
PubMed: 38942714
DOI: 10.1016/j.urolonc.2024.05.005 -
Academic Radiology Jun 2024The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for...
RATIONALE AND OBJECTIVES
The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for patients with stage I non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
The databases PubMed was searched from inception to November 2023 to identify relevant studies. Statistical analyses were performed with R version 3. 6. 3.
RESULTS
Thirty-three studies involving 1400 patients were finally included. According to our study, the incidence of patients with stage I NSCLC who were older than 60 years old was 98 % (95 % CI [94-100 %]); the lesions were mostly located in RUL (Right Upper Lobe) and LUL (Left Upper Lobe), and the incidence of the two sites was 29 % (95 % CI [23-35 %]) and 27 % (95 % CI [21-33 %]), respectively; the types of lung cancers mainly included adenocarcinoma, squamous carcinoma, and large-cell lung cancer, of which adenocarcinoma accounted for the largest proportion of 63 % (95 % CI [56-70 %]); the causes of death were mainly categorized into cancer-related (57 %, 95 %CI[40-74 %]) and noncancer-related (40 %, 95 %CI [23-58 %]); the common complications in the postoperative period were pneumothorax and pain, with the incidence of 33 % (95 %CI[24-44 %]) and 33 % (95 %CI[19-50 %]), and the rate of the postoperative complications in MWA was slightly higher than those in RFA; the local recurrence rate was 23 % (95 %CI[17-29 %]) and the distant recurrence rate was 18 % (95 %CI[7-32 %]); the pooling result showed the rate of 1-, 2-, 3-, and 5-year survival rate were 96 %, 81 %, 68 %, and 42 %, the Cancer-specific survival (CSS) rates at 1, 2, 3, and 5 years were 98 %, 88 %, 75 %, and 58 %, Disease-free survival (DFS) rates at 1, 2, 3, and 5 years were 87 %, 63 %, 57 %, and 42 %, there were no significant differences existed between the RFA group and MWA group in survival rate, CSS and DFS.
CONCLUSION
Ablation therapy is safe and effective for stage I NSCLC patient. MWA and RFA have comparable efficacy, safety, and prognosis, which could be recommended for patients with stageⅠNSCLC, especially for patients who cannot tolerate open surgery.
PubMed: 38942645
DOI: 10.1016/j.acra.2024.05.038 -
Clinical Oncology (Royal College of... Jun 2024To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of...
AIMS
To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease.
BACKGROUND
The incidence of endometrial cancer has risen by around 60% since the 90's. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females.
METHODS
This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson's chi-square test.
RESULTS
The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence.
CONCLUSIONS
The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.
PubMed: 38942617
DOI: 10.1016/j.clon.2024.06.001 -
Boletin Medico Del Hospital Infantil de... 2024This essay challenges the idea of progress as technological development in relation to medicine by focusing on people rather than things. It analyzes how the prevalence...
This essay challenges the idea of progress as technological development in relation to medicine by focusing on people rather than things. It analyzes how the prevalence of such an idea of progress leads contemporary societies to a technofetishism that degrades community life and medical practice, contributing to the medicalization of social life. It is argued that the realization of technological potentialities depends on their forms of use, that the main motive of technological development is unlimited profit, and the priority developments are those that enhance social control which maintains the status quo. Intelligence as an intelligence quotient is criticized by proposing it as an attribute of the human being as a whole, manifested in the ways of thinking and acting of human beings in their circumstances, where affectivity and critical thinking are essential for their development; it is emphasized that its antecedent is the harmonic concert of planetary life, which contrasts with the prevailing human disharmony. It is proposed that artificial intelligence is the latest creation of technofetishism, which deposits vital attributes in technology, and that its use will accentuate the degradation of human and planetary life. Another idea of medical progress is proposed, based on forms of organization that is conducive to the development of inquisitive, critical, and collaborative skills that promote permanent improvement, whose distant horizon is dignified progress: the spiritual, intellectual, moral, and convivial sublimation of collectivities in harmony with the planetary ecosystem.
Topics: Artificial Intelligence; Humans; Medicalization
PubMed: 38941644
DOI: 10.24875/BMHIME.M24000071 -
Boletin Medico Del Hospital Infantil de... 2024This essay questions, with regard to medicine, the idea of progress as technological development by focusing on people rather than things. It analyzes how the...
This essay questions, with regard to medicine, the idea of progress as technological development by focusing on people rather than things. It analyzes how the predominance of such an idea of progress converts today's societies to techno-fetishism that degrades community life and medical practice, contributing to the medicalization of social life. It is argued that the realization of technological potentialities depends on their forms of use; that the main motive of technological development is unlimited profit and that priority developments are those that enhance the social control that maintains the status quo. The intelligence as an intelligence quotient is criticized by proposing it as an attribute of the human being as a whole, manifested in the ways of thinking and proceeding of people in their circumstances, where affectivity and critical thinking are essential for their development; it is emphasized that its antecedent is the harmonic concert of planetary life that contrasts with the prevailing human disharmony. It is proposed that artificial intelligence is the most recent creation of techno-fetishism that deposits vital attributes in technology and that its forms of use will accentuate the degradation of human and planetary life. Another idea of medical progress is proposed, based on forms of organization conducive to the development of inquisitive, critical and collaborative skills that promote permanent improvement, whose distant horizon is dignifying progress: spiritual, intellectual, moral and convivial sublimation of collectivities in harmony with the planetary ecosystem.
Topics: Artificial Intelligence; Humans; Medicalization; Intelligence; Medicine
PubMed: 38941639
DOI: 10.24875/BMHIM.24000007