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Human Cell Jul 2024Approximately 3-5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors....
Approximately 3-5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months). In this study, we established tumoroids (PDT-LUAD#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALK v3 mutation. PDT-LUAD#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1). Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDT-LUAD#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.
Topics: Humans; Lung Neoplasms; Anaplastic Lymphoma Kinase; Carcinoma, Squamous Cell; Oncogene Proteins, Fusion; Mutation; Protein Kinase Inhibitors; Animals; Cell Transformation, Neoplastic; Adenocarcinoma; Tumor Suppressor Protein p53; Adenocarcinoma of Lung; Crizotinib; Cell Line, Tumor; Carcinoma, Non-Small-Cell Lung
PubMed: 38829559
DOI: 10.1007/s13577-024-01085-8 -
Oncology Letters Jul 2024There has been rapid advancement in the development of neoadjuvant therapy for non-small cell lung cancer (NSCLC), which holds great promise as an effective treatment...
There has been rapid advancement in the development of neoadjuvant therapy for non-small cell lung cancer (NSCLC), which holds great promise as an effective treatment strategy. Some clinical trials have confirmed that immunotherapy in combination with chemotherapy can be a recommended first-line regimen for neoadjuvant treatment of NSCLC. The present study describes the case of a male patient aged 65 years who was diagnosed with stage IIIA (cT2N2M0) adenosquamous carcinoma of the lung. After the administration of two cycles of neoadjuvant immunotherapy (sintilimab) in combination with chemotherapy, stable disease was observed in the primary tumor, whereas partial remission was detected in the mediastinal lymph nodes based on imaging assessment. The patient underwent an immediate upper lobectomy of the left lung. Pathological analysis revealed a complete response in the primary lesion, with only minimal presence of tumor cells observed in the lymph nodes surrounding the mediastinum and bronchi. This indicated that the present neoadjuvant therapy could be used in the treatment of stage III adenosquamous lung carcinoma; however, to conclusively determine its efficacy, further studies targeting this specific cancer type are essential.
PubMed: 38807664
DOI: 10.3892/ol.2024.14448 -
Journal of Surgical Case Reports May 2024A female in her 60s with vague abdominal symptoms was found to have a pancreatic mass in her CT scan. A core needle biopsy done endoscopically demonstrated a poorly...
A female in her 60s with vague abdominal symptoms was found to have a pancreatic mass in her CT scan. A core needle biopsy done endoscopically demonstrated a poorly differentiated adenocarcinoma. The patient completed nine cycles of neoadjuvant systemic mFOLFIRINOX. Repeat staging demonstrated a partial radiographic response. She underwent an open pylorus-preserving pancreatoduodenectomy with segmental superior mesenteric vein resection with primary reconstruction (ISGPS Type 3). The final pathology demonstrated a poorly differentiated adenosquamous carcinoma, R1 margin status. The case report demonstrates the effect of mFOLFIRINOX on pancreatic adenosquamous (PASC) carcinoma with a review of the microscopic pictures following the neoadjuvant therapy. It can be postulated that glandular component being the major component in a PASC has a good response to mFOLFIRINOX like that seen in pancreatic ductal adenocarcinoma with some presumed effect on the squamous component as well. From the above case report, we are proposing that mFOLFIRINOX can be an effective chemotherapy regime in the management of PASC.
PubMed: 38803839
DOI: 10.1093/jscr/rjae345 -
Animals : An Open Access Journal From... May 2024Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary...
Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.
PubMed: 38791685
DOI: 10.3390/ani14101469 -
Current Oncology (Toronto, Ont.) Apr 2024This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer-mixed adenosquamous...
This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer-mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate.
Topics: Humans; Male; Liver Neoplasms; Middle Aged; Prostatic Neoplasms; Carcinoma, Adenosquamous
PubMed: 38785459
DOI: 10.3390/curroncol31050178 -
Frontiers in Oncology 2024To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and...
The prognostic effect of tumor volume, reduction ratio, and cumulative doses on external beam radiotherapy with central-shielding method and image-guided adaptive brachytherapy for cervical cancer.
OBJECTIVE
To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTV D) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer.
METHODS
Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression.
RESULTS
A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All < 0.05). In this group, the patients with a cumulative CTV D < 69.6 Gy showed significantly worse PFS and LC ( = 0.042 and = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors ( = 0.045, = 0.009 and = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor ( = 0.041).
CONCLUSION
The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors.
PubMed: 38774419
DOI: 10.3389/fonc.2024.1366777 -
Heliyon May 2024Lung adenosquamous carcinoma (ASC) is a rare tumor with high invasive and metastatic potential. Few studies have explored metastatic patterns in patients with...
BACKGROUND
Lung adenosquamous carcinoma (ASC) is a rare tumor with high invasive and metastatic potential. Few studies have explored metastatic patterns in patients with advanced-stage ASC.
METHODS
Patients diagnosed with ASC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015 were selected. Descriptive statistics were obtained to characterize the metastatic sites of the study participants. The Kaplan-Meier method was applied to compare survival curves among patients with different metastatic patterns. Cox regression analysis was performed to evaluate risk factors for metastasis.
RESULTS
A total of 858 eligible patients with ASC were enrolled; the mean age was 71.5 years (standard deviation ± 7.8 years). There was a slightly higher proportion of male patients (54.0 %). A total of 63.2 % of patients harbored single-site metastasis (median OS: 5 months), 23.6 % of patients had two-site metastasis (median OS: 4 months), and approximately 10 % of patients harbored three or more sites metastasis (median OS: 3 months). Bone (56.9 %) was the most frequent site of metastasis (median OS: 4 months), followed by lung metastasis (37.6 %, median OS: 5 months), liver metastasis (22.1 %, median OS: 5 months), and brain metastasis (21.4 %, median OS: 4 months). Chemotherapy decreased the risk of death by 70 % (HR = 0.296, 95 % CI 0.241-0.363), 70 % (HR = 0.302, 95 % CI 0.224-0.406), 78 % (HR = 0.218, 95 % CI 0.151-0.314), and 70 % (HR = 0.302, 95 % CI 0.231-0.396) in patients harboring bone, liver, brain and lung metastases, respectively. The brain increased the risk of death by 50 % (HR = 1.501, 95 % CI 1.209-1.865), 64 % (HR = 1.644, 95 % CI 1.126-2.402), and 128 % (HR = 2.284, 95 % CI 1.653-3.157) in patients harboring bone, liver and lung metastases, respectively.
CONCLUSION
Patients with advanced-stage ASC have unfavorable outcomes. Early detection and aggressive treatment can improve patients outcomes.
PubMed: 38765098
DOI: 10.1016/j.heliyon.2024.e30641 -
Journal of Gastrointestinal Oncology Apr 2024The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is a potent negative regulator of T-cell-mediated immune response that is...
BACKGROUND
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is a potent negative regulator of T-cell-mediated immune response that is upregulated in many neoplasms. Pancreaticobiliary adenosquamous carcinoma (PB-ASC) is an aggressive cancer that carries a poorer prognosis compared with pure pancreaticobiliary adenocarcinoma (PB-AC). To date, there is little published information regarding PD-L1 expression in PB-ASC. The aim of the study was to examine the relationship between PD-L1 expression and tumor-infiltrating lymphocytes in PB-ASC and PB-AC.
METHODS
We evaluated 15 PB-ASCs (10 pancreatic, 5 gallbladder) and 34 control PB-ACs (22 pancreatic ductal, and 12 gallbladder) for tumor expression of PD-L1 using anti-PD-L1 (E1L3N) antibody. All tumors were classified into three immune phenotypes: immune inflamed (II), immune excluded (IE), and immune desert (ID) according to the distribution of tumor-infiltrating lymphocytes in tumor tissues.
RESULTS
The frequency of PD-L1 expression was significantly higher in PB-ASC (10/15; 66.7%) than in PB-AC (3/34; 8.8%). In PB-ASC, PD-L1 expression occurred exclusively in the squamous component in six cases, exclusively in the glandular component in one case, and in both the squamous and the glandular components in three cases. PD-L1 expression in PB-ASC was irrespective of the tumor immune status, whereas its expression in PB-AC was observed only in tumors with the II or IE phenotype. The ID phenotype was relatively rare (4/15; 26.7%) in PB-ASC compared with PB-AC (22/34; 65%; P=0.02).
CONCLUSIONS
PB-ASCs are notably enriched in inflammatory response and showed significantly higher PD-L1 expression than PB-AC (P<0.001), suggesting a potential therapeutic role for immune checkpoint inhibitors in managing patients with PB-ASC.
PubMed: 38756636
DOI: 10.21037/jgo-24-9 -
Annals of Surgical Oncology May 2024Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for...
BACKGROUND
Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus. We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC.
METHODS
CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig. 1).
RESULTS
The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig. 2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion, while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1).
CONCLUSIONS
This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.
PubMed: 38730117
DOI: 10.1245/s10434-024-15380-z -
PloS One 2024It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression....
It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.
Topics: Adult; Female; Humans; Middle Aged; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Shelterin Complex; Telomerase; Telomere-Binding Proteins; Tripeptidyl-Peptidase 1; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms
PubMed: 38722833
DOI: 10.1371/journal.pone.0298118