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Therapeutic Advances in Urology 2024Renal cell carcinoma (RCC) is the most common type of kidney cancer and is divided into two distinct subtypes, clear cell renal cell carcinoma (ccRCC) and non-clear cell... (Review)
Review
Renal cell carcinoma (RCC) is the most common type of kidney cancer and is divided into two distinct subtypes, clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC). Although many treatments exist for RCC, these are largely based on clinical trials performed in ccRCC and there are limited studies on the management of nccRCC. Non-clear cell RCC consists of multiple histological subtypes: papillary, chromophobe, translocation, medullary, collecting duct, unclassified, and other rare histologies. Due to variations in pathogenesis and therapeutic response, therapy should be tailored to specific variant histologies. For patients with localized nccRCC, surgical resection remains the gold standard. In the metastatic setting, the standard of care has yet to be clearly defined, and most guidelines recommend clinical trial participation. General therapeutic options include immunotherapy, either as monotherapy or in combination, targeted therapies such as vascular endothelial growth factor tyrosine kinase inhibitors and MET inhibitors, and chemotherapy in certain subtypes. Here we present a review of the incidence and pathogenesis of the various subtypes, as well as available clinical data to support therapeutic recommendations for these subtypes. We also highlight currently available clinical trials in nccRCC and future directions in investigating novel treatment modalities tailored to patients with variant histology.
PubMed: 38434237
DOI: 10.1177/17562872241232578 -
EJNMMI Research Mar 2024We recently introduced radiohybrid (rh)-based minigastrin analogs e.g., DOTA-rhCCK-18 (DOTA-D-Dap(p-SiFA)-(D-γ-Glu)-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH), that revealed...
BACKGROUND
We recently introduced radiohybrid (rh)-based minigastrin analogs e.g., DOTA-rhCCK-18 (DOTA-D-Dap(p-SiFA)-(D-γ-Glu)-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH), that revealed substantially increased activity retention in the tumor. However, one major drawback of these first generation rh-based cholecystokinin-2 receptor (CCK-2R) ligands is their elevated activity levels in the kidneys, especially at later time points (24 h p.i.). Therefore, this study aimed to reduce kidney retention with regard to a therapeutic use via substitution of negatively charged D-glutamic acid moieties by hydrophilic uncharged polyethylene glycol (PEG) linkers of various length ((PEG) to (PEG)). Furthermore, the influence of differently charged silicon-based fluoride acceptor (SiFA)-moieties (p-SiFA: neutral, SiFA-ipa: negatively charged, and SiFAlin: positively charged) on in vitro properties of minigastrin analogs was evaluated. Out of all compounds evaluated in vitro, the two most promising minigastrin analogs were further investigated in vivo.
RESULTS
CCK-2R affinity of most compounds evaluated was found to be in a range of 8-20 nM (by means of apparent IC), while ligands containing a SiFA-ipa moiety displayed elevated IC values. Lipophilicity was noticeably lower for compounds containing a D-γ-glutamate (D-γ-Glu) moiety next to the D-Dap(SiFA) unit as compared to their counterparts lacking the additional negative charge. Within this study, combining the most favorable CCK-2R affinity and lipophilicity, [Lu]Lu-DOTA-rhCCK-70 (DOTA-D-Dap(p-SiFA)-D-γ-Glu-(PEG)-D-γ-Glu-(PEG)-Trp-(N-Me)Nle-Asp-1-Nal-NH; IC: 12.6 ± 2.0 nM; logD: - 1.67 ± 0.08) and [Lu]Lu-DOTA-rhCCK-91 (DOTA-D-Dap(SiFAlin)-D-γ-Glu-(PEG)-D-γ-Glu-(PEG)-Trp-(N-Me)Nle-Asp-1-Nal-NH; IC: 8.6 ± 0.7 nM; logD = - 1.66 ± 0.07) were further evaluated in vivo. Biodistribution data of both compounds revealed significantly reduced (p < 0.0001) activity accumulation in the kidneys compared to [Lu]Lu-DOTA-rhCCK-18 at 24 h p.i., leading to enhanced tumor-to-kidney ratios despite lower tumor uptake. However, overall tumor-to-background ratios of the novel compounds were lower than those of [Lu]Lu-DOTA-rhCCK-18.
CONCLUSION
We could show that the reduction of negative charges within the linker section of radiohybrid-based minigastrin analogs led to decreased activity levels in the kidneys at 24 h p.i., while maintaining a good tumor uptake. Thus, favorable tumor-to-kidney ratios were accomplished in vivo. However, further optimization has to be done in order to improve tumor retention and general biodistribution profile.
PubMed: 38429609
DOI: 10.1186/s13550-024-01087-5 -
Archives of Endocrinology and Metabolism Feb 2024Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a... (Review)
Review
Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Phenylurea Compounds; Adenocarcinoma; Prognosis
PubMed: 38427812
DOI: 10.20945/2359-4292-2023-0375 -
Asian Pacific Journal of Cancer... Feb 2024Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral...
INTRODUCTION
Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral infections, has been extensively investigated. Recently, the link between HBV infection and breast cancer patients has garnered attention. The present research aims to assess the prevalence of HBV markers among women diagnosed with breast cancer in Ahvaz city, Iran.
MATERIALS AND METHODS
Serum specimens were procured from 90 patients who had been clinically diagnosed with breast cancer. The age of the patients ranged from 29 to 80 years, with a mean age of 49.42±10.7. Histological examination of biopsy specimens revealed that 75 (83.33%) were ductal, 11 (8.88%) lobular, 2 (2.22%) mucinous, 1 (1.11%) medullary, and 1 (1.11%) was metastatic. The serum samples were subjected to initial HBsAg and anti-HBc testing via ELISA. Samples that tested seropositive (HBsAg + anti-HBc) were subsequently analyzed for the S region of HBV through nested PCR and DNA sequencing. Finally, a phylogenetic tree was constructed for positive HBV DNA tests.
RESULTS
Among the 5/90 (5.55%) cancer patients, it was found that 3 (3.33%) cases of ductal carcinoma and one (1.11%) lobular carcinoma displayed positivity for HBV markers (HBsAg, anti-HBc, HBV PCR). Notably, one (1.11%) patient with ductal carcinoma solely demonstrated anti-HBc positivity. The phylogenetic tree analysis of the S region revealed that all HBV strains identified were categorized as genotype D.
CONCLUSION
The statistical analysis did not reveal any significant findings (p= 0.315) in the distribution of cancer types across different age groups. Among patients diagnosed with breast cancer, a notable prevalence of 5.5% was observed in HBV markers. The dominant HBV genotype among breast cancer patients was identified as genotype D.
Topics: Humans; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Hepatitis B virus; Hepatitis B; Hepatitis B Surface Antigens; Breast Neoplasms; Prevalence; Phylogeny; Hepatitis B Antibodies; Carcinoma, Ductal; DNA, Viral
PubMed: 38415541
DOI: 10.31557/APJCP.2024.25.2.547 -
Translational Cancer Research Jan 2024Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and...
BACKGROUND
Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients.
METHODS
A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy.
RESULTS
There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors.
CONCLUSIONS
MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.
PubMed: 38410238
DOI: 10.21037/tcr-23-858 -
Discover Oncology Feb 2024Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy,... (Review)
Review
BACKGROUND
Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy, highlighting a need for innovative approaches.
METHODS
We analyzed 658 articles and 87 eligible clinical trials using bibliometric tools and database searches, including annual publication and citation trends, were executed using Web of Science, CiteSpace, and VOS Viewer.
RESULTS
Post-2018, there is a surge in thyroid cancer immunotherapy research, primarily from China and the University of Pisa. Of the 87 trials, 32 were Phase I and 55 were Phase II, mostly exploring combination therapies involving immune checkpoint inhibitors.
CONCLUSION
The study's dual approach verifies the swift advancement of thyroid cancer immunotherapy from diverse perspectives. Immune checkpoint inhibitors have become the preferred regimen for advanced MTC and ATC in late therapeutic lines. However, since ICB plays a pivotal role in ATC, current clinical trial data show that ATC patients account for more and the curative effect is more accurate. Anticipated future developments are inclined toward combination regimens integrating immunotherapy with chemotherapy or targeted therapies. Emerging approaches, such as bispecific antibodies, cytokine-based therapies, and adoptive cell therapies like CAR-T and TCR-T, are exhibiting considerable potential. Upcoming research is expected to concentrate on refining the tumor immune milieu and discovering novel biomarkers germane to immunotherapeutic interventions.
PubMed: 38403820
DOI: 10.1007/s12672-024-00904-6 -
Molecular Imaging and Radionuclide... Feb 2024We present the case of a 58-year-old man with advanced medullary thyroid carcinoma who had a treatment history with different types of modalities. In the follow-up, the...
We present the case of a 58-year-old man with advanced medullary thyroid carcinoma who had a treatment history with different types of modalities. In the follow-up, the patient had rising calcitonin and CEA levels. Metastatic lymph nodes, liver, and bone metastases with varying degrees of uptake were detected on F-fluorodeoxyglucose (FDG) and Ga-DOTATATE positron emission tomography/computed tomography (PET/CT). Ga prostate-specific membrane antigen (PSMA) PET/CT was performed to explore whether the patient might have a chance for PSMA-targeted radionuclide therapy, and increased PSMA expression was noted in most of the metastatic lesions, even some of which have higher PSMA uptake than F-FDG and Ga-DOTATATE.
PubMed: 38390812
DOI: 10.4274/mirt.galenos.2023.47855 -
The Journal of Veterinary Medical... Apr 2024Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia....
Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia. RICT is a rare tumor in dogs, originating from renal interstitial cells. While several renal tumors such as renal lymphoma, adenocarcinoma, carcinoma, sarcoma, fibrosarcoma and nephroblastoma may cause polycythemia, polycythemia caused by RICT has never been reported in dogs. The tumors in both dogs were solitary and lied within cortex or cortico-medullary junction. Histopathology revealed spindle-shaped cells suggesting mesenchymal origin, with no mitotic figures suggesting that the tumors in both dogs were benign. Following surgical removal of the affected kidney, serum erythropoietin level and polycythemia normalized in both dogs.
Topics: Male; Dogs; Animals; Polycythemia; Leydig Cell Tumor; Erythropoietin; Dog Diseases; Kidney Neoplasms
PubMed: 38383003
DOI: 10.1292/jvms.23-0413 -
Translational Oncology May 2024The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune...
BACKGROUND
The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping.
METHODS
Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation.
RESULTS
Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established.
CONCLUSION
Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.
PubMed: 38382228
DOI: 10.1016/j.tranon.2024.101889 -
Endocrine-related Cancer May 2024The incidence rate of medullary thyroid carcinoma (MTC) continues to grow, along with its mortality rate in the USA. However, the subgroup trends in MTC have not yet...
Subgroup analysis of steadily increased trends in medullary thyroid carcinoma incidence and mortality in the USA, 2000-2020: a population-based retrospective cohort study.
The incidence rate of medullary thyroid carcinoma (MTC) continues to grow, along with its mortality rate in the USA. However, the subgroup trends in MTC have not yet been established. This population-based retrospective cohort study was based on the Surveillance, Epidemiology, and End Results (SEER) 17/12 registry database. Subgroup analysis was performed through clinicopathological and treatment-related characteristics. Annual average percentage change (AAPC) was calculated using joinpoint regression analysis. A total of 3833 MTC patients and 536 death cases were diagnosed in the SEER database. Between 2000 and 2019, the incidence (AAPC = 1.64) and mortality (AAPC = 3.46) rates of MTC continued to rise. Subgroup analysis showed the proportion of elderly patients (65-84 years) gradually increased in incidence between 2000 and 2020. Patients with early-stage tumors, such as tumors ≤20 mm, showed the same trends. Aspects of treatment, the implementation rate of total thyroidectomy (AAPC = 0.38) and lymph node dissection (AAPC = 1.06) also increased persistently in almost all of the age subgroups. The incidence and mortality of MTC consistently increased from 2000 to 2019. Subgroup analysis indicated a significant increase in elderly patients and early-stage patients, and more attention should be paid to the management of these increased subgroups.
Topics: Humans; United States; Aged; Retrospective Studies; Incidence; SEER Program; Thyroid Neoplasms; Carcinoma, Neuroendocrine
PubMed: 38376827
DOI: 10.1530/ERC-23-0319