Impact of Low BMI and Nutritional Status on Quality of Life and Disease Outcome in Breast Cancer Patients: Insights From a Tertiary Cancer Center in India.

This study investigates the impact of Body Mass Index (BMI) on Quality of Life (QoL) and treatment outcomes in breast cancer (BC) patients, particularly focusing on underweight individuals with compromised nutritional status. A nonrandomized prospective study comprising 121 newly diagnosed patients across various BMI categories utilized FACT-B & FACIT-Sp-12 questionnaires. Follow-ups occurred at baseline, during (3rd and 6th), and after (12th month) anthracycline-taxane chemotherapy, either sequentially or concomitantly. Patients with low BMI (<18.5 kg/m2; 53.7%) exhibited significantly poorer QoL, marked by compromised nutritional indicators (low MUAC and SFT). Repeated measures ANOVA identified significant correlations between BMI groups in functional, social, and emotional QoL aspects (p < 0.05), with no notable differences in other domains. A Chi-square (ꭓ2) test underscored a significant link between BMI and treatment response (p < 0.0001), showing higher rates of non-responders among underweight patients (p = 4.259e-14). The study advocates pretreatment consultation with a dietitian as standard care for Indian BC patients, offering complimentary nutritional support for improved QoL outcomes and treatment responses.

Pyrazole-based and N,N-diethylcarbamate functionalized some novel aurone analogs: Design, synthesis, cytotoxic evaluation, docking and SAR studies, against AGS cancer cell line.

The present study involves the design, synthesis, and biological evaluation of a series of thirty-three, pyrazole-based and N,N-diethylcarbamate functionalized, novel aurone analogs, against AGS cancer cell line. These novel aurone analogs are obtained from the reaction of pyrazole-based 6-hydroxyaurones with diethyl carbamoyl chloride using mild basic reagent. The cytotoxic activities of these compounds were evaluated against a human gastric adenocarcinoma cell line (AGS) and disclosed some potential outcomes as several analogs were found to have cytotoxicity better than the reference drugs Oxaliplatin and Leucovorin. The structure-activity relationship (SAR) study further unveiled the critical role of replacing the hydroxyl group in ring A with a carbamoyl group for cytotoxic activity. Among these aurone analogs, 8e and 8f, with IC50 values of 6.5 ± 0.024 µM and 6.6 ± 0.035 µM, respectively, are identified as the most active compounds. Molecular docking studies were conducted against HER2, a human epidermal growth factor involved in gastric and ovarian cancer, to investigate the binding interactions between the compounds and the protein HER2, where7e and 8e exhibited maximum interactions.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

OBJECTIVE: Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. MATERIALS AND METHODS: 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. RESULTS: The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences (P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis (P = 0.015). CONCLUSIONS: TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Effect of adjuvant autologous platelet concentrates on secondary repair of alveolar clefts: A systematic review and meta-analysis.

OBJECTIVE: To review the existing evidence on the adjuvant use of autologous platelet concentrates (APCs) with iliac crest bone graft (ICBG) in the reconstruction of the secondary alveolar cleft. METHODS: Electronic databases were searched systematically until November 2022. Clinical trials comparing the three-dimensional radiological outcomes of patients who underwent secondary alveolar bone grafting (SABG) with ICBG and APCs to those with ICBG alone and the radiological outcomes assessed 6 months after surgery were included. Two authors performed the study selection and the assessment of the risk of bias. Meta-analysis was performed using the random-effects model to determine the risk ratio (RR) for developing wound dehiscence and the mean difference (MD) with a 95% confidence interval (CI) for the percentage of newly formed bone. RESULTS: Nine studies (seven RCT and two CCT) were included with a low to high risk of bias. At the 6-month follow-up, the study group revealed insignificant results regarding the percentage of newly formed bone (MD = 6.49; 95% CI: -0.97, 13.94; p = .09; χ2  = 0.01; I2  = 71%). In addition, the overall risk of developing wound dehiscence was lower in the study group (RR = 0.34; 95% CI: 0.15, 0.78; p = .01; χ2  = 0.67; I2  = 0%). CONCLUSION: Currently, there is insufficient evidence to support the adjuvant use of APCs with ICBG on enhanced bone regeneration following secondary alveolar bone grafting. However, combining ICBG and APCs might be beneficial in reducing the risk of developing wound dehiscence.

Emerging Futuristic Targeted Therapeutics: A Comprising Study Towards a New Era for the Management of TNBC.

Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal. The critical need for more effective therapies underscores the urgency to discover potent novel treatments, including molecular and immune targets, as well as emerging strategies. This review provides a comprehensive analysis of conventional treatment approaches and explores emerging molecular and immune-targeted therapeutics, elucidating their mechanisms to address the existing obstacles for a more effective management of triple-negative breast cancer.

Unlocking DCAFs To Catalyze Degrader Development: An Arena for Innovative Approaches.

Chemically induced proximity-based targeted protein degradation (TPD) has become a prominent paradigm in drug discovery. With the clinical benefit demonstrated by certain small-molecule protein degraders that target the cullin-RING E3 ubiquitin ligases (CRLs), the field has proactively strategized to tackle anticipated drug resistance by harnessing additional E3 ubiquitin ligases to enrich the arsenal of this therapeutic approach. Here, we endeavor to explore the collaborative efforts involved in unlocking a broad range of CRL4DCAF for degrader drug development. Throughout the discussion, we also highlight how both conventional and innovative approaches in drug discovery can be taken to realize this objective. Moving ahead, we expect a greater allocation of resources in TPD to pursue these high-hanging fruits.

A Rare Incidence of Nonsyndromic Mandibular Incisor Agenesis in a Three-generation Family: Case Report and Literature Review.

Hypodontia is an inherited condition involving the absence of one to six teeth. The permanent dentition is the most frequently affected; however, it may also affect the primary dentition. A congenitally missing tooth (CMT) is the most common dental abnormality, with the missing mandibular second premolar, maxillary lateral incisor, maxillary second premolar, and mandibular central incisor accounting for 90% of CMT in hypodontia studies. The etiology of CMT has been attributed to environmental and genetic contributing factors, with the latter having a strong influence. It may occur in isolation or in association with syndromes. Congenitally missing mandibular incisor is more common in the Asian population and females. Depending on the number and location of missing teeth, hypodontia may be a considerable issue for the clinician since it may impact occlusal balance, mastication, speech, and esthetics and often requires a multidisciplinary approach. Missing mandibular incisors are of particular interest to orthodontists because of the possibility of mandibular retrognathism, the potential for the development of malocclusion, and difficulty in achieving a balanced occlusion. This case report describes the skeletal and dental features of a nonsyndromic familial occurrence of missing mandibular incisors in three generations. A comprehensive literature search was also performed to review the familial cases with missing mandibular incisors. How to cite this article: Selvaraj M, Sennimalai K, Samrit VD, et al. A Rare Incidence of Nonsyndromic Mandibular Incisor Agenesis in a Three-generation Family: Case Report and Literature Review. Int J Clin Pediatr Dent 2023;16(2):388-395.

Quantitative Evaluation of Pentraxin-3 in Peri-Miniscrew Implant Crevicular Fluid in Patients Undergoing Orthodontic Treatment: A Prospective Study.

OBJECTIVE: To assess the levels of Pentraxin-3 (PTX3) in peri-miniscrew implant crevicular fluid (PMICF) before and after orthodontic force application Material and Methods: This study included 40 miniscrew implants (MSI) sites in 11 orthodontic patients with high arch discrepancy requiring first premolar extraction using maximum anchorage mechanics for the retraction of anterior teeth. After alignment, the en-masse anterior retraction was carried out using the MSI-supported direct anchorage method. PMICF was collected from the crevice of MSI using Periopaper strips 1.2µl (Oraflow Inc. USA) after one hour, 24 hours, and three weeks of MSI insertion and after one hour, 24 hours, seven days, three weeks, and six weeks of the force application. Samples were quantitatively analyzed for PTX3 levels through enzyme-linked immunosorbent assay (ELISA). RESULTS: The trend in the change of PTX3 levels was evaluated using the Wilcoxon signed-rank test. The mean concentration of PTX3 immediately after MSI insertion was 1.19 ng/ml, significantly higher than after 3 weeks after MSI insertion (0.72 ng/ml), which may correspond to the baseline. After loading, the mean PTX3 concentration increased significantly with the peak at 24 hrs (1.28 ng/ml), followed by a gradual decline till the completion of the study (0.5 ng/ml). CONCLUSION: After MSI insertion, a rise in PTX3 levels in PMICF suggests an underlying inflammatory process. The slow decline in PTX3 level and return to the baseline after loading suggests an adaptive bone response to the stimulus.

Binder's syndrome: A narrative review.

AIM: The classical features of Binder's syndrome (BS) have been widely reported, yet there is a lack of information on diagnostic and treatment challenges. Therefore, we aimed to review the literature on various aspects, including the role of a multidisciplinary approach in the management of BS. METHODS: A thorough literature search was performed on PubMed, Scopus, Embase, Ovid, Web of Science, EBSCOhost, and Google Scholar using the keywords"Maxillonasal dysplasia", "Maxillonasal dysostosis", "nasomaxillary hypoplasia", "Binder type", "Binder syndrome", "Binder phenotype", and "OMIM 155050". In addition, the articles published in the English language from the inception of the database until June 2021 were considered. RESULTS: The search of different databases yielded 958 publications, out of which 145 relevant articles were reviewed. The studies were categorised by year of publication, study design, and theme. Most of the studies were case reports (42%) followed by case series (19%). The most reported topic was based on different surgical techniques (42%). Finally, the results were synthesised into a narrative review. CONCLUSIONS: The need for a multidisciplinary approach involving clinicians from different specialities is highlighted. Future research is warranted to develop concrete clinical guidelines for the management of this syndrome.

A quantitative analysis of macrophage-colony-stimulating factor in peri-miniscrew implant crevicular fluid before and after orthodontic loading.

OBJECTIVES: To analyze macrophage-colony-stimulating factor (M-CSF), a bone remodeling biomarker in the peri-miniscrew implant crevicular fluid (PMICF) after insertion and orthodontic loading. MATERIALS AND METHODS: This prospective study included 40 miniscrew implant (MSI) sites in 10 subjects undergoing fixed orthodontic mechanotherapy utilizing miniscrew anchorage. After dental alignment, miniscrews were inserted between the second premolar and first molar roots. After 21 days of insertion, MSIs were direct loaded with closed-coil springs (200 g force) for en masse retraction of anterior teeth. PMICF was collected with Periopaper™ strips from the gingival crevice around MSIs at six time points (T1-T6: 1 hour, 1 day, 21 days postinsertion, and 7, 21, and 42 days postloading). PMICF was quantified for M-CSF by enzyme-linked immunosorbent assay. Paired comparison of mean M-CSF concentrations before and after loading stages (T1-T6) was made using the Wilcoxon signed-rank test. RESULTS: The mean M-CSF concentration showed a significant peak at T3 (21 days postinsertion; 12.646 pg/mL; T1 vs T3: P < .0001). After orthodontic loading of miniscrews, M-CSF levels increased to 13.570 pg/mL at T4 (7 days after loading; T1 vs T4: P < .001) and maintained at a plateau to T5 (21 days postloading; 11.994 pg/mL). However, the difference between preloading and postloading was not statistically significant (T3 vs T4). CONCLUSIONS: The maximum M-CSF activity around MSIs was observed at around 3 weeks of miniscrew insertion, suggesting underlying bone remodeling after surgical injury. However, orthodontic force on MSIs did not cause any significant surge in M-CSF levels postloading.

PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer.

Triple-negative breast cancer lacks an expression of ER, PR, and Her-2, has a poor prognosis, and there are no target therapies available. Therapeutic options to treat TNBC are limited and urgently needed. Strong evidence indicates that molecular signaling pathways have a significant function to regulate biological mechanisms and their abnormal expression endows with the development of cancer. PIM kinase is overexpressed in various human cancers including TNBC which is regulated by various signaling pathways that are crucial for cancer cell proliferation and survival and also make PIM kinase as an attractive drug target. One of the targets of the STAT3 signaling pathway is PIM1 that plays a key role in tumor progression and transformation. In this review, we accumulate the current scenario of the PIM-STAT3 axis that provides insights into the PIM1 and STAT3 inhibitors which can be developed as potential co-inhibitors as prospective anticancer agents.

In-silico and in-vitro investigation of STAT3-PIM1 heterodimeric complex: Its mechanism and inhibition by curcumin for cancer therapeutics.

The functional activity among STAT3 and PIM1, are key signaling events for cancer cell function. Curcumin, a diarylheptanoid isolated from turmeric, effectively inhibits STAT3 signaling. Selectively, we attempted to address interactions of STAT3, PIM1 and Curcumin for therapeutic intervention using in silico and in vitro experimental approaches. Firstly, protein-protein interactions (PPI) between STAT3-PIM1 by molecular docking studies reflected salt bridges among Arg279 (STAT3)-Glu140 (PIM1) and Arg282 (STAT3)-Asp100 (PIM1), with a binding affinity of -38.6 kcal/mol. Secondly, molecular dynamics simulations of heterodimeric STAT3-PIM1 complex with curcumin revealed binding of curcumin on PIM-1 interface of the complex through hydrogen bonds (Asp155) and hydrophobic interactions (Leu13, Phe18, Val21, etc.) with a binding energy of -7.3 kcal/mol. These PPIs were confirmed in vitro by immunoprecipitation assays in MDA-MB-231 cells. Corroborating our results, expression levels of STAT3 and PIM1 decreased after curcumin treatment. We observed that PIM1 interacts with STAT3 and these functional interactions are disrupted by curcumin. The calculated band energy gap of heterodimeric STAT3-PIM1-Curcumin complex was of 9.621 kcal/mol. The present study revealed the role of curcumin in STAT3/PIM1 signaling and its binding affinity to the complex for design of advanced cancer therapeutics.

Evaluation of numerical rating scale and neuropathic pain symptom inventory pain scores in advanced ovarian carcinoma patients undergoing surgery and first-line chemotherapy.

BACKGROUND AND AIM: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel. METHODS: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles. RESULTS: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment (P > 0.05) and between the responder and non-responder categories (P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences (P = 0.001) in the neoadjuvant chemotherapy group. CONCLUSION: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment. RELEVANCE FOR PATIENTS: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India.

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

Effects of submucosally administered platelet-rich plasma on the rate of tooth movement.

OBJECTIVES: To evaluate the effects of submucosally administered platelet-rich plasma (PRP) on the rate of maxillary canine retraction. Levels of soluble receptor activator of nuclear factor-κb ligand (sRANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) were also measured over 2 months. MATERIALS AND METHODS: This split-mouth trial involved 20 sites in 10 subjects randomly assigned to PRP (experimental) side and control side. After alignment, the freshly prepared PRP was injected submucosally distal to the experimental side maxillary canine, and retraction was performed using NiTi closed-coil springs (150 g) on 0.019 × 0.025-inch stainless steel wire. The rate of canine movement was assessed using digital model superimposition at 0, 30, and 60 days. The OPG and sRANKL were assayed using enzyme-linked immunosorbent assay from GCF collected at 0, 1, 7, 21, 30, and 60 days. RESULTS: Twenty sites were analyzed using paired t test. The rate of tooth movement increased significantly by 35% on the PRP side compared with the control side in the first month (P = .0001) and by 14% at the end of the second month (P = .015). Using the Mann-Whitney U test, OPG levels were found to be significantly decreased on the 7th (P = .003) and 30th day on the PRP side (P = .01), while sRANKL became detectable by the third week postinjection on the PRP side (P = .069). CONCLUSIONS: Submucosal injection of platelet-rich plasma significantly increased tooth movement during the 60-day observation period. Local injection of PRP significantly altered the levels of OPG and sRANKL in GCF.

Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC), which shows immunohistochemically negative expression of hormone receptor i.e., Estrogen receptor and Progesterone receptor along with the absence of Human Epidermal Growth Factor Receptor-2 (HER2/neu). In Indian scenario the prevalence of BC is 26.3%, whereas, in West Bengal the cases are of 18.4%. But the rate of TNBC has increased up to 31% and shows 27% of total BC. Conventional chemotherapy is effective only in the initial stages but with progression of the disease the effectivity gets reduced and shown almost no effect in later or advanced stages of TNBC. Thus, TNBC patients frequently develop resistance and metastasis, due to its peculiar triple-negative nature most of the hormonal therapies also fails. Development of chemoresistance may involve various factors, such as, TNBC heterogeneity, cancer stem cells (CSCs), signaling pathway deregulation, DNA repair mechanism, hypoxia, and other molecular factors. To overcome the challenges to treat TNBC various targets and molecules have been exploited including CSCs modulator, drug efflux transporters, hypoxic factors, apoptotic proteins, and regulatory signaling pathways. Moreover, to improve the targets and efficacy of treatments researchers are emphasizing on targeted therapy for TNBC. In this review, an effort has been made to focus on phenotypic and molecular variations in TNBC along with the role of conventional as well as newly identified pathways and strategies to overcome challenge of chemoresistance.

Comparison of the efficacy of two-time versus one-time micro-osteoperforation on maxillary canine retraction in orthodontic patients: A split-mouth randomized controlled clinical trial.

BACKGROUND: Micro-osteoperforation (MOP), a minimally invasive technique for accelerating the rate of orthodontic tooth movement has been research extensively, but with varied clinical results. OBJECTIVE: To compare the efficacy of one-time versus two-time micro-osteoperforation on the rate of maxillary canine retraction, its influence on anchorage loss, canine angulation and the levels of interleukin (IL-1ß) in gingival crevicular fluid (GCF). MATERIALS AND METHODS: The split-mouth study included 16 patients in which the left and right sides were randomly allocated to the control side (one-time MOP) and experimental side (two-time MOP). MOP was performed on both sides distal to the maxillary canines and canine retraction was carried out using NiTi closed coil springs (150gm) and direct anchorage with miniscrew implants. The second MOP was performed on experimental side one month after the first MOP. The rate of canine movement was assessed using 3D model superimposition over a period of six months. The type of tooth movement, anchorage loss and levels of IL-1ß were also evaluated. RESULTS: Sixteen patients (mean age, 17.87±3.34 years) were analysed for a rate of canine retraction, anchorage loss, and type of tooth movement, while 15 patients were analysed for IL-1ß. The rate was significantly higher on two-time MOP side after two months (P<0.001). No statistical difference was found in anchorage loss and controlled tipping of canines was observed. The IL-1ß levels immediately after 2nd MOP were significantly higher than 1st MOP (P<0.001). CONCLUSION: The two-time intervention of MOP is more efficacious than one-time MOP in accelerating tooth movement.