Bone mineral density (BMD) plays a crucial role in diagnosing and treating various systemic chronic diseases. Patients with multiple or singular spinal metastasis (SM) are typically in advanced stages of systemic cancer, often leading to significant alterations in BMD. The present study investigated the prognostic value of perioperative Hounsfield units (HU) as a surrogate independent marker for estimated BMD in patients with SM after surgical treatment (ST).

HU values, serving as a surrogate for estimated BMD, were measured from circular regions of interest (ROIs) in the spine -first lumbar vertebra (L1)- from routine preoperative staging computed tomography (CT) scans in 187 patients after ST. The estimated BMD was stratified into pathologic and physiologic values and correlated with survival parameters in our cohorts.

Median L1 BMD of 92 patients (49%) with pathologic BMD was 79.5 HU (IQR 67.25-93.5) compared to 145 HU (IQR 123-166) for 95 patients (51%) with physiologic BMD (p ≤ 0.001). Patients with pathological BMD exhibited a median overall survival of 8 months compared to 12.2 months in patients with physiologic BMD (p = 0.006). Multivariable analysis revealed pathologic BMD as an independent negative prognostic predictor for increased 1 year mortality (AUC: 0.637, 95% CI: 0.556-0.718; p = 0.001).

The present study demonstrates that decreased perioperative BMD values, as derived from HU measurements, may represent a previously unrecognized negative prognostic factor in patients of SM after ST. The estimated perioperative BMD could emerge as an individualized, readily available potential biomarker for prognostic, treatment, and discussion of affected patients with SM.

The interaction between breast cancer and stromal tissues varies significantly from patient to patient, greatly impacting cancer prognosis. However, conventional models struggle to accurately replicate these patient-specific interactions. Herein, a novel breast cancer-adipose composite tissue model capable of precisely adjusting the inter-tissue interaction is developed. The composite tissue model is produced through precise embedded bioprinting of breast-cancer spheroids and live-adipose-tissue ink. This model possessed not only precisely patterned cancer spheroids but also well-preserved intrinsic extracellular matrices (ECMs) and heterogeneous cell populations of adipose tissue (AT). Evaluation results successfully demonstrated that the bioprinted composite model can precisely regulate adipokine secretion, drug resistance, and cancer-cell invasion characteristics by adjusting the distance between the cancer spheroids and adipose tissue. The utility of the model is validated using adipokine-targeted therapies (C-compound/SC600125 (SC), AG 490 (AG), and Metformin (MET)). Interestingly, the inhibition of cancer cell proliferation and invasion by these adipokine-targeted drugs nearly doubled as the tissue distance decreased. This suggests that the efficacy of the drugs can be precisely evaluated using the new model. These findings underscore the potential of the developed composite model to replicate patient-specific crosstalk, thereby offering a promising platform for the sophisticated evaluation of various breast-cancer therapies.

Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM. Compared with cutaneous melanoma, ALM showed a lower frequency of tumor-reactive CD8 clusters and an enrichment of regulatory T cells with direct tumor recognition ability, suggesting a suppressive immune microenvironment in ALM. Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.

To spatially map the position of the facial artery and vein along the inferior border of the mandible based on specific facial reference points.

This cross-sectional study included 40 sides of 21 formalin-fixed cadaver heads (11 female, 10 male) with a mean age of 72.92 ± 11.72 years. Superficial dissection was performed to visualize the facial artery and vein at the inferior border of the mandible (FA and FV). Measurements were taken from the FA and FV to various facial landmarks using a digital caliper and medical protractor. Statistical analysis was conducted using Shapiro-Wilk, independent sample t-tests, and paired sample t-tests.

The mean distance between FA and FV was 6.20 ± 2.97 mm. Distances from FA and FV to gnathion, oral commissure, nasal wing, lateral canthus, angle of mandible, intertragic notch, and Manson's point were determined, with no significant differences found between sides and genders (p > 0.05). The closest distances from FA and FV to the line between the intertragic notch and oral commissure were 38.63 ± 4.86 mm and 37.78 ± 5.28 mm, respectively. The angular measurements of FA and FV with inferior border of mandible were 61.45 ± 13.71 and 76.56 ± 10.17 degrees, respectively. The angle between intertragic notch, FA and oral commisure was 102.40 ± 11.12 degrees.

The detailed measurements and analysis provided in this study aim to enhance the precision of surgical interventions involving the facial artery and vein. The practical localization methods proposed can assist in minimizing the risk of vascular injuries, improving outcomes in reconstructive and aesthetic procedures.

Griseofulvin (GF), which is mainly extracted from Penicillium griseofulvum, is a heat-resistant, chlorine-containing non-polyene antifungal antibiotic. Previous research shows that GF has a variety of pharmacological effects, such as anti-inflammatory, antifungal, antiviral, and antitumor effects. In recent years, GF has received extensive attention for its antitumor effects as a natural compound, offering a low price, a wide range of uses, and other beneficial characteristics. However, no comprehensive review of GF pharmacological activity in tumors has been published so far. In order to fully elucidate the antitumor activities of GF, this review focuses on the antitumor potential and toxicity of GF and its derivatives, based on a literature search using PubMed, Web of Science, and other databases, to lay a good foundation for further research of GF and the development of new drugs for antitumor activities.

Heat shock protein 90 (HSP90) plays a crucial role in cancer cell growth and metastasis by stabilizing overexpressed signaling proteins. Inhibiting HSP90 has emerged as a promising anti-cancer strategy. In this study, we aimed to develop and characterize a HSP90-targeted molecular imaging probe, [64Cu]Cu-DOTA-BDA-GM, based on a specific HSP90 inhibitor, geldanamycin (GM), for PET imaging of cancers. GM is modified at the C-17 position with 1,4-butane-diamine (BDA) and linked to 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for 64Cu radiolabeling. We evaluated the probe's specific binding to HSP90-expressing cells using Chinese hamster ovary (CHO) cells and breast cancer cells including MDA-MB-231, MDA-MB-435S, MCF7, and KR-BR-3 cell lines. A competition study with non-radioactive GM-BDA yielded an IC50 value of 1.35 ± 0.14 nM, underscoring the probe's affinity for HSP90. In xenograft models of MDA-MB-231 breast cancer, [64Cu]Cu-DOTA-BDA-GM showcased targeted tumor localization, with significant radioactivity observed up to 18 h post-injection. Blocking studies using unlabeled GM-BDA and treatment with the anticancer drug Vorinostat (SAHA), which can affect the expression and activity of numerous proteins, such as HSPs, confirmed the specificity and sensitivity of the probe in cancer targeting. Additionally, PET/CT imaging in a lung metastasis mouse model revealed increased lung uptake of [64Cu]Cu-DOTA-BDA-GM in metastatic sites, significantly higher than in non-metastatic lungs, illustrating the probe's ability to detect metastatic breast cancer. In conclusion, [64Cu]Cu-DOTA-BDA-GM represents a sensitive and specific approach for identifying HSP90 expression in breast cancer and metastases, offering promising implications for clinical diagnosis and monitoring.

The Ppy gene encodes pancreatic polypeptide (PP) secreted by PP- or γ-cells, which are a subtype of endocrine cells localised mainly in the islet periphery. For a detailed characterisation of PP cells, we aimed to establish PP cell lines. To this end, we generated a mouse model harbouring the SV40 large T antigen (TAg) in the Rosa26 locus, which is expressed upon Ppy-promoter-mediated Cre-loxP recombination. Whereas Insulin1-CreERT-mediated TAg expression in beta cells resulted in insulinoma, surprisingly, Ppy-Cre-mediated TAg expression resulted in the malignant transformation of Ppy-lineage cells. These mice showed distorted islet structural integrity at 5 days of age compared with normal islets. CK19+ duct-like lesions contiguous with the islets were observed at 2 weeks of age, and mice developed aggressive pancreatic ductal adenocarcinoma (PDAC) at 4 weeks of age, suggesting that PDAC can originate from the islet/endocrine pancreas. This was unexpected as PDAC is believed to originate from the exocrine pancreas. RNA-sequencing analysis of Ppy-lineage islet cells from 7-day-old TAg+ mice showed a downregulation and an upregulation of endocrine and exocrine genes, respectively, in addition to the upregulation of genes and pathways associated with PDAC. These results suggest that the expression of an oncogene in Ppy-lineage cells induces a switch from endocrine cell fate to PDAC. Our findings demonstrate that Ppy-lineage cells may be an origin of PDAC and may provide novel insights into the pathogenesis of pancreatic cancer, as well as possible therapeutic strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Tumors of the spine are challenging in terms of diagnoses and interdisciplinary treatment. This study was conducted to evaluate and characterize a large multicenter cohort of surgically treated spine tumor patients.Data of the German Spine Society (DWG) were used to characterize a cohort of all surgically treated spine tumor cases that were registered between 2017 and 2021. Subgroup analysis was performed for tumor entity, tumor localization, height of most severely affected segments, surgical treatment, and demographic parameters.In total, there were 9686 cases, of which 6747 were "malignant", 1942 were "primary benign", 180 were "tumor-like lesions", and 488 were "other" spinal tumors. Subgroups showed differences in number of affected segments as well as localization. There were further significant differences in surgical complication rates (p = 0.003), age (p < 0.001), morbidity (p < 0.001), and duration of surgery (p = 0.004).This is a representative study on spinal tumors from a large spine registry and allows for the epidemiological characterization of surgically treated tumor subgroups and quality control of registry data.

Current treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT.

Single center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR.

15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7-10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1-1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery).

50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Prostate cancer is the second most commonly diagnosed cancer in men. The mammalian insulin-like growth factor (IGF) family is made up of three ligands (IGF-I, IGF-II, and insulin), three receptors (IGF-I receptor (IGF-1R), insulin receptor (IR), and IGF-II receptor (IGF-2R)), and six IGF-binding proteins (IGFBPs). IGF-I and IGF-II were identified as potent mitogens and were previously associated with an increased risk of cancer development including prostate cancer. Several reports showed controversy about the expression of the IGF family and their connection to prostate cancer risk due to the high degree of heterogeneity among prostate tumors, sampling bias, and evaluation techniques. Despite that, it is clear that several IGF family members play a role in prostate cancer development, metastasis, and androgen-independent progression. In this review, we aim to expand our understanding of prostate tumorigenesis and regulation through the IGF system. Further understanding of the role of IGF signaling in PCa shows promise and needs to be considered in the context of a comprehensive treatment strategy.

Existing data on the histopathological correlation of testicular tumors with lymph node prognosis have been poorly explored. We aimed to investigate the relationship of the histopathological properties of testicular tumors with lymph nodes and their involvement with chemoresistance and heterogeneity of testicular tumors.

Patients with non-seminomatous germ cell tumor (NSGCT) were selected for histopathological correlation of testicular tumor with lymph nodes and its relationship with chemoresistance and heterogeneity. Histopathological and radiological parameters associated with the risk of chemoresistance and tumor progression were measured pre- and post-chemotherapy. Binomial logistic regression and Kaplan-Meier analysis were implemented to determine the predictors of progression and adverse overall patient survival. All categorical variables were analyzed using the Chi-square test, while Pearson's R coefficient determined the correlation.

Male patients who were diagnosed with NSGCT from March 2017 to December 2018 at Guwahati Medical College, Guwahati, India, were included in this study. Lymph node groups were predominantly incriminated with the EYST or EYS groups and minimally linked with the pure E and YCS groups. Furthermore, the highest number of lymph node stations was associated with pre-chemotherapy. In salvage chemotherapy in the form of VIP, we found exciting outcomes, as approximately 41% of cases responded positively, especially in the EYS group.

Our study classifies NSGCT according to the most favorable histopathological grouping and explores the tumoral response in different intrinsic and extrinsic variables. Our analysis can serve as a triumphant histopathological nomogram for a sublime management protocol to deal with the onerous histological pairing in NSGCT.

Colorectal cancer (CRC) screening rates in the United States remain persistently below guideline targets, partly due to suboptimal patient utilization and provider reimbursement. To guide long-term national utilization estimates and set reasonable screening adherence targets, this study aimed to quantify trends in utilization of and reimbursement for CRC screenings using Medicare claims.

Inflation-adjusted reimbursements and utilization volume associated with each CRC screening code were abstracted from Medicare claims between 2000 and 2019. Screenings, screenings/100 000 enrolees and reimbursement/screening were analysed with linear regression and compared with the equality of slopes tests. Average reimbursement per screening was compared using analysis of variance with Dunnett's T3 multiple comparisons test.

The growth rate of multitarget stool DNA tests (mt-sDNA)/100 000 was the highest at 170.4 screenings/year (R2 = 0.99, p ≤ 0.001), while that of faecal occult blood tests/100 000 was the lowest at -446.4 screenings/year (R2 = 0.90, p ≤ 0.001) (p ≤ 0.001). Provider reimbursements averaged $546.95 (95% CI $520.12-$573.78) per mt-sDNA screening, significantly higher than reimbursements for all invasive screenings. Only FOBTs significantly increased in reimbursement per screening at $0.62/year (R2 = 0.91, p ≤ 0.001).

We derived forecastable trend numbers for utilization and provider reimbursement. Faecal immunochemical tests/100 000 and mt-sDNA screenings/100 000 increased most rapidly during the entire study period. The number of nearly all invasive screenings/100 000 decreased rapidly; the number of colonoscopies/100 000 increased slightly, probably due to superior diagnostic strength. These trends indicate the that replacement of other invasive modalities with accessible noninvasive screenings will account for much of future screening behaviour and thus reductions in CRC incidence and mortality, especially given providers' reimbursement incentive to screen average-risk patients with stool-based tests.

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.

Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection.

From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM.

The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74).

Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.

Rhabdomyosarcoma of the female genital tract often involves the vagina and cervix. It usually occurs in infants and children. Such tumors are uncommon in the uterus, especially in adults. Treatment options are based on studies of younger individuals.

Rhabdomyosarcoma (RMS) is a malignant mesenchymal neoplasm with a tendency to differentiate into skeletal muscle cells. RMS is an aggressive tumor that tends to develop in children and younger patients. A vast majority of genital tract RMSs occur in the vagina and cervix. Such tumors rarely occur in adults. Usually, these tumors either occur as a component of a biphasic uterine tumor (carcinosarcoma or adenosarcoma) or can be a pure heterologous tumor. Pure uterine RMSs are extremely rare in adult patients and difficult to diagnose. Accurate diagnosis of these tumors depends on precise histopathological evaluation. The present report describes a rare case of embryonal RMS of the uterus in a postmenopausal female and explores the most recent literature. The aim is to strengthen the existing literature and aid clinicians in the management of similar cases. A 64-year-old postmenopausal female presented with a history of abdominal pain associated with abdominal distension, per vaginal bleeding, and foul-smelling discharge for 6 months. A transabdominal ultrasound revealed a bulky uterus with a well-circumscribed heterogeneous lesion. Histopathology confirmed the diagnosis of high-grade embryonal RMS within the corpus region of the uterus. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, followed by adjuvant chemotherapy to prevent relapse of the disease. Six months after oncological care has passed, the patient remains symptoms-free without evidence of recurrence or metastasis.

Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC.

We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3).

Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022).

The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 μg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15-17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32-6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association.

Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by a more precise molecular based one. As validated, convenient, and cost-effective molecular-based tests emerge, molecular diagnostics will play a greater role in the clinical and histologic diagnosis of melanoma. Artificial intelligence augmented clinical and histologic diagnosis of melanoma is expected to make the process more streamlined and efficient. A more accurate model of prognosis and staging of melanoma is emerging based on molecular understanding melanoma. This contribution summarizes the recent advances in melanoma epidemiology, classification, diagnosis, and prognosis.

Prostate cancer (PCa) has become the major health problem and the leading causes of cancer mortality among men. PCa often progresses from an early androgen-dependent form of cancer to a late (metastatic) androgen-independent cancer, for which no effective treatment options are available. Current therapies target testosterone depletion, androgen axis inhibition, androgen receptor (AR) downregulation and regulation PSA expression. These conventional treatment options, however, are intense and pose severe side effects. From the past few years, plant-derived compounds or phytochemicals have attracted much attention by the researchers worldwide for their promising approach in inhibiting the development and growth of cancer. This review emphasizes mechanistic role of promising phytochemicals on PCa. This review imparts to score anticancer efficacy of promising phyto-agents luteolin, fisetin, coumestrol and hesperidin with focus on the mechanistic action in management and treatment of PCa. These phytocompounds were also selected for their best binding affinity with the ARs on the basis of molecular docking studies.

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.

Recently, endoplasmic reticulum stress related gene (ERS) markers have performed very well in predicting the prognosis of tumor patients.

The differentially expressed genes in Oral squamous cell carcinoma (OSCC) were obtained from TCGA and GTEx database. Three prognosis-related and differentially expressed ERSs were screened out by Least Absolute Selection and Shrinkage Operator (Lasso) regression to construct a prognostic risk model. Receiver Operating Characteristic Curve (ROC), riskplots and survival curves were used to verify the model's accuracy in predicting prognosis. Multi-omics analysis of immune infiltration, gene mutation, and stem cell characteristics were performed to explore the possible mechanism of OSCC. Finally, we discussed the model's clinical application value from the perspective of drug sensitivity.

Three genes used in the model (IBSP, RDM1, RBP4) were identified as prognostic risk factors. Bioinformatics analysis, tissue and cell experiments have fully verified the abnormal expression of these three genes in OSCC. Multiple validation methods and internal and external datasets confirmed the model's excellent performance in predicting and discriminating prognosis. Cox regression analysis identified risk score as an independent predictor of prognosis. Multi-omics analysis found strong correlations between risk scores and immune cells, cell stemness index, and tumor mutational burden (TMB). It was also observed that the risk score was closely related to the half maximal inhibitory concentration of docetaxel, gefitinib and erlotinib. The excellent performance of the nomogram has been verified by various means.

A prognostic model with high clinical application value was constructed. Immune cells, cellular stemness, and TMB may be involved in the progression of OSCC.

Early detection is crucial for the treatment and prognosis of oral cancer, a potentially lethal condition. Tumor markers are abnormal biological byproducts produced by malignant cells that may be found and analyzed in a variety of bodily fluids, including saliva. Early detection and appropriate treatment can increase cure rates to 80-90% and considerably improve quality of life by reducing the need for costly, incapacitating medicines. Salivary diagnostics has drawn the interest of many researchers and has been proven to be an effective tool for both medication monitoring and the diagnosis of several systemic diseases. Since researchers are now searching for biomarkers in saliva, an accessible bodily fluid, for noninvasive diagnosis of oral cancer, measuring tumor markers in saliva is an interesting alternative to blood testing for early identification, post-treatment monitoring, and monitoring high-risk lesions. New molecular markers for oral cancer detection, treatment, and prognosis have been found as a result of developments in the fields of molecular biology and salivary proteomics. The numerous salivary tumor biomarkers and how they relate to oral cancer and pre-cancer are covered in this article. We are optimistic that salivary protein biomarkers may one day be discovered for the clinical detection of oral cancer because of the rapid advancement of proteomic technology.

In our recent study, advanced disease stage and nonreceipt of surgery were the most important mediators of the racial disparity in breast cancer survival. The purpose of this study was to quantify the racial disparity in these two intermediate outcomes and investigate mediation by the more proximal mediators of insurance status and neighborhood poverty.

This was a cross-sectional study of non-Hispanic Black and non-Hispanic White women diagnosed with first primary invasive breast cancer in Florida between 2004 and 2015. Log-binomial regression was used to obtain prevalence ratios (PR) with 95% confidence intervals (CIs). Multiple mediation analysis was used to assess the role of having Medicaid/being uninsured and living in high-poverty neighborhoods on the race effect.

There were 101,872 women in the study (87.0% White, 13.0% Black). Black women were 55% more likely to be diagnosed with advanced disease stage at diagnosis (PR, 1.55; 95% CI, 1.50-1.60) and nearly twofold more likely to not receive surgery (PR, 1.97; 95% CI, 1.90-2.04). Insurance status and neighborhood poverty explained 17.6% and 5.3% of the racial disparity in advanced disease stage at diagnosis, respectively; 64.3% remained unexplained. For nonreceipt of surgery, insurance status explained 6.8% while neighborhood poverty explained 3.2%; 52.1% was unexplained.

Insurance status and neighborhood poverty were significant mediators of the racial disparity in advanced disease stage at diagnosis with a smaller impact on nonreceipt of surgery. However, interventions designed to improve breast cancer screening and receipt of high-quality cancer treatment must address additional barriers for Black women with breast cancer.

Retrospective Cohort Study.

Octogenarians living with spinal metastases are a challenging population to treat. Our objective was to identify the rate, types, management, and predictors of complications and survival in octogenarians following surgery for spinal metastases.

A retrospective review of a prospectively collected cohort of patients aged 80 years or older who underwent surgery for metastatic spinal tumor treatment between 2008 and 2019 were included. Demographic, intraoperative, complications, and postoperative follow-up data was collected. Cox proportional hazards regression and logistic regression were used to associate variables with overall survival and postoperative complications, respectively.

78 patients (mean 83.6 years) met inclusion criteria. Average operative time and blood loss were 157 minutes and 615 mL, respectively. The median length of stay was 7 days. The overall complication rate was 31% (N = 24), with 21% considered major and 7% considered life-threatening or fatal. Blood loss was significantly associated with postoperative complications (OR = 1.002; P = 0.02) and mortality (HR = 1.0007; P = 0.04). Significant associations of increased risk of death were also noted with surgeries with decompression, and cervical/cervicothoracic index level of disease. For deceased patients, median time to death was 4.5 months. For living patients, median follow-up was 14.5 months. The Kaplan-Meier based median overall survival for the cohort was 11.6 months (95% CI: 6.2-19.1).

In octogenarians undergoing surgery with instrumentation for spinal metastases, the median overall survival is 11.6 months. There is an increased complication rate, but only 7% are life-threatening or fatal. Patients are at increased risk for complications and mortality particularly when performing decompression with stabilization, with increasing intraoperative blood loss, and with cervical/cervicothoracic tumors.

Paclitaxel in combination with ramucirumab is the standard of care second-line therapy in gastro-esophageal adenocarcinoma (GEA). As the number of taxane pretreated patients in the perioperative or first-line setting is increasing, it is unknown whether these patients benefit from re-applying a taxane in using the combination of paclitaxel and ramucirumab. Furthermore, the rates of neurotoxicity with first-line FOLFOX or FLOT range from 30%-70%, making second-line taxane-containing therapy less suitable to a meaningful portion of patients. This patient group is likely to benefit from a taxane-free second-line chemotherapy regimen, such as FOLFIRI and ramucirumab (FOLFIRI-Ram). Therefore, the RAMIRIS phase III trial evaluates the effects of the regimen of FOLFIRI-Ram in the second-line treatment after a taxane-based chemotherapy in patients with advanced GEA.

The RAMIRIS trial is a randomized, open-label, multicenter phase II/III study comparing treatment of FOLFIRI-Ram (arm A) with paclitaxel and ramucirumab (arm B). The Phase II is already closed with 111 enrolled patients. In the phase III, 318 taxane-pretreated patients with advanced GEA will be recruited and randomized 1:1 to FOLFIRI (5-FU 2400 mg/m2 over 46 h i.v., irinotecan 180 mg/m2 i.v.; 5-FU 400 mg/m2 bolus; leucovorin 400 mg/m2 i.v.; on day 1 and 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m2 (days 1, 8, 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm B). The primary endpoints are overall survival (OS) and objective overall response rate (ORR). Secondary endpoints are progression-free survival (PFS), disease control rate and safety and quality of life as assessed by EORTC-QLQ-C30 questionnaire.

The already completed RAMIRIS phase II demonstrated feasibility and efficacy of FOLFIRI-Ram. Especially docetaxel-pretreated patients seemed to markedly benefit from FOLFIRI-Ram, with favorable response- and PFS rates and lower toxicity. This offers a rationale for the phase III trial. If the RAMIRIS III trial transfers and confirms the results, they will affect the current treatment guidelines, recommending the combination therapy of FOLFIRI-Ram for taxane-pretreated patients with advanced GEA.

NCT03081143 Date of registration: 13.11.2015.

Lung cancer cells overexpress mucin 1 (MUC1) and active subunit MUC1-CT. Although a peptide blocks MUC1 signalling, metabolites targeting MUC1 are not well studied. AICAR is a purine biosynthesis intermediate.

Cell viability and apoptosis were measured in AICAR-treated EGFR-mutant and wild-type lung cells. AICAR-binding proteins were evaluated by in silico and thermal stability assays. Protein-protein interactions were visualised by dual-immunofluorescence staining and proximity ligation assay. AICAR-induced whole transcriptomic profile was determined by RNA sequencing. EGFR-TL transgenic mice-derived lung tissues were analysed for MUC1 expression. Organoids and tumours from patients and transgenic mice were treated with AICAR alone or in combination with JAK and EGFR inhibitors to evaluate treatment effects.

AICAR reduced EGFR-mutant tumour cell growth by inducing DNA damage and apoptosis. MUC1 was one of the leading AICAR-binding and degrading proteins. AICAR negatively regulated JAK signalling and JAK1-MUC1-CT interaction. Activated EGFR upregulated MUC1-CT expression in EGFR-TL-induced lung tumour tissues. AICAR reduced EGFR-mutant cell line-derived tumour formation in vivo. Co-treating patient and transgenic mouse lung-tissue-derived tumour organoids with AICAR and JAK1 and EGFR inhibitors reduced their growth.

AICAR represses the MUC1 activity in EGFR-mutant lung cancer, disrupting protein-protein interactions between MUC1-CT and JAK1 and EGFR.

Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution though regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first-in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen.

Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from January 1, 1970, to August 1, 2022.

PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.

The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM).

AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated.

There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054).

In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

The aims of the study are to explore spinal magnetic resonance imaging (MRI)-based radiomics to differentiate spinal metastases from primary nonsmall cell lung cancer (NSCLC) or breast cancer (BC) and to further predict the epidermal growth factor receptor (EGFR) mutation and Ki-67 expression level.

In total, 268 patients with spinal metastases from primary NSCLC (n = 148) and BC (n = 120) were enrolled between January 2016 and December 2021. All patients underwent spinal contrast-enhanced T1-weighted MRI before treatment. Two- and 3-dimensional radiomics features were extracted from the spinal MRI images of each patient. The least absolute shrinkage and selection operator regression were applied to identify the most important features related to the origin of the metastasis and the EGFR mutation and Ki-67 level. Radiomics signatures (RSs) were established using the selected features and evaluated using receiver operating characteristic curve analysis.

We identified 6, 5, and 4 features from spinal MRI to develop Ori-RS, EGFR-RS, and Ki-67-RS for predicting the metastatic origin, EGFR mutation, and Ki-67 level, respectively. The 3 RSs performed well in the training (area under the receiver operating characteristic curves: Ori-RS vs EGFR-RS vs Ki-67-RS, 0.890 vs 0.793 vs 0.798) and validation (area under the receiver operating characteristic curves: Ori-RS vs EGFR-RS vs Ki-67-RS, 0.881 vs 0.744 vs 0.738) cohorts.

Our study demonstrated the value of spinal MRI-based radiomics for identifying the metastatic origin and evaluating the EGFR mutation status and Ki-67 level in patients with NSCLC and BC, respectively, which may have the potential to guide subsequent individual treatment planning.

Tumors arising within the parotid encompass a heterogeneous mix of benign and malignant neoplasms and other tissue growths. The purpose of this study was to determine the association between the location of intraparotid masses and the risk of malignancy. A retrospective cohort study was performed of patients diagnosed with parotid tumors following open tumor excision. The primary predictor variable was the location of the epicenter of the tumor in three-dimensional space, as determined from preoperative imaging. Other variables were patient demographics and clinical parameters. The primary outcome variable was the final histopathologic diagnosis of a benign or malignant process. A χ² analysis was performed to test for any significant associations between demographic, clinical, and radiographic factors in relation to the outcome, and backwards stepwise logistic regression analysis was used to control for variables. Both increasing age (P = 0.002) and the presence of local pain (P = 0.020) were associated with malignancy. Tumors located anterior to the posterior border of the retromandibular vein had 2.18 times higher odds of malignancy (95% confidence interval 1.13-4.21; P = 0.020). Multivariate regression analysis suggested that patient age, the presence of pain, and tumor location anterosuperiorly and superoinferiorly could all assist in determining the odds of malignancy.

To explore the direct and indirect heat damage zone of radiofrequency ablation (RFA) in porcine vertebrae and to verify the safety of RFA in a vascularized vertebral tumor model.

RFA was performed in the porcine lumbar vertebrae. Magnetic resonance (MR) imaging, hematoxylin and eosin (HE), and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) were used to assess the extent of direct and indirect injuries after RFA. The cavity of lumbar vertebrae was made, and the adjacent muscle flap was used to fill the cavity to make a vertebrae tumor model. RFA was performed in the vascularized vertebral tumor model.

T1-weighted images showed a hypointensive region in the center surrounded by a more hypointensive rim on day 0 and 14. T2-weighted images showed that RFA zone was hypointensive on day 0. On day 7, hypointensity was detected in the center surrounded by a hyperintensive rim. HE showed that the RFA zone could be clearly observed on day 14. Thin bone marrow loss areas were seen around the RFA zone, which was consistent with the hyperintensive rim on the T2-weighted images. TUNEL showed a large number of apoptotic cells in the RFA zone. During RFA in the vertebral tumor model, the temperature of all monitoring positions was less than 45 °C.

Using in vivo experiments, the effective zone of RFA was evaluated by MR imaging and pathology, and the direct and indirect damage range were obtained. The safety of RFA was verified by RFA in a vascularized vertebral tumor model.

Lung cancer is the leading cause of cancer death globally. There is a causal relationship between smoking and lung cancer; nearly 90% of cases are caused by cigarette smoking.

To investigate the public interest in the relationship between lung cancer and tobacco smoking through an analysis of searches in Google Trends over the past 16 years.

We conducted a systematic search through Google Trends using the search terms "lung cancer" and "smoking" to identify the numbers of lung cancer and tobacco smoking searches in populations from Turkey, the United States, and the whole world between January 1, 2004 and December 31, 2019.

Online searches that reflect public awareness are nearly identical for both lung cancer and smoking; however, there is an inverse correlation between population interest and incidences of lung cancer and smoking. Furthermore, the numbers of searches on lung cancer and smoking decrease gradually in Turkey, in the world, and in the United States over the years, displaying a slight seasonal pattern.

Informative and educational campaigns covering the whole year are required to raise awareness of the relationship between lung cancer and smoking and keep people argus-eyed.

Male breast cancer is rare but its incidence and mortality are increasing in the United States, with racial/ethnic disparities in survival reported. There is limited evidence for cardiotoxicity of cancer treatment among men with breast cancer. We evaluated the relation between breast cancer treatment and cardiovascular disease (CVD) mortality among men and investigated the salient roles that race/ethnicity play on this relation. Data were from 5216 men with breast cancer aged ≥ 40 years from the Surveillance, Epidemiology, and End Results program who were diagnosed from 2000 to 2019 and underwent surgery. Competing risk models were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). During a median follow-up of 5.6 years, 1914 deaths occurred with 25% attributable to CVD. In multivariable-adjusted models, men who received chemotherapy had elevated risk for CVD (HR: 1.55, 95%CI: 1.18-2.04). This risk was higher among Hispanic men (HR: 3.96, 95%CI: 1.31-12.02) than non-Hispanic Black and non-Hispanic White men. There was no significant association between radiotherapy and CVD deaths. In this population-based study, treatment with chemotherapy was associated with elevated risk of CVD mortality in men with breast cancer. Racial/ethnic disparities in the association of chemotherapy and CVD mortality were observed.

Patients with endometrial cancer (EC) frequently have metastases to lungs, extra-pelvic nodes, and liver. Although an uncommon occurrence, cases of EC metastasis to bone, prevalently in vertebral bone, have also been reported. The objective of this study was to analyze clinical and pathological profiles of patients with EC metastatic to vertebral bone. We carried out a retrospective case series on surgically treated patients for this pathology. From 2001 to 2021, out of 775 patients with bone metastasis, 1.6% had bone metastasis from EC. The median time between the diagnosis of primary tumor and that of bone metastases was 31.5 months. Solitary bone lesion was present in 7 patients and lumbar vertebrae were the segments most affected. Pathological fractures in 46.2% of patients and spinal pain in all were present. In terms of location, 46.2% of bone metastases resided within the anterior section of the vertebra, while the remaining presented an extension within the anterior and posterior sections, with 46.1% of cases showing an extradural extra-osseous extension and paraspinous envelope. Median survival after diagnosis of bone metastasis was 11.5 months. Vertebral bone metastasis in EC is a rare phenomenon, with severe prognosis. An in-depth understanding of this topic may guide future management and treatment decisions, thus improving life expectancy and quality.

Lung cancer is the second leading cause of cancer-related mortality globally, and non-small-cell lung cancer accounts for most lung cancer cases. Nanotechnology-based drug-delivery systems have exhibited immense potential in lung cancer therapy due to their fascinating physicochemical characteristics, in vivo stability, bioavailability, prolonged and targeted delivery, gastrointestinal absorption and therapeutic efficiency of their numerous chemotherapeutic agents. However, traditional chemotherapeutics have systemic toxicity issues; therefore, dietary polyphenols might potentially replace them in lung cancer treatment. Polyphenol-based targeted nanotherapeutics have demonstrated interaction with a multitude of protein targets and cellular signaling pathways that affect major cellular processes. This review summarizes the various molecular mechanisms and targeted therapeutic potentials of nanoengineered dietary polyphenols in the effective management of lung cancer.

Metastatic castration-resistant prostate cancer (mCRPC) with high mortality has seriously threatened men's health. Bifunctional agents simultaneously degrade and antagonize androgen receptor (AR), display robust AR signaling pathway blockade, and show the therapeutic prospect for mCRPC. Herein, systemic structural modifications on the C-3, C-6, and C-17 positions of galeterone led to the discovery of 67-b with the dual functions of AR antagonism and degradation. In vitro, 67-b exhibited excellent antiproliferative activity and potent AR degradation activity in different PCa cells (LNCaP and 22RV1), as well as outstanding antagonistic activity against wild-type and mutant (W741L, T877A, and F876L) ARs. In vivo, 67-b effectively inhibited the growth of hormone-sensitive organs in the Hershberger assay and exhibited tumor regression in the enzalutamide-resistant (c4-2b-ENZ) xenograft model. These results confirmed 67-b to be a promising AR degrader and antagonist for the treatment of mCRPC patients.