Common Subtype Research Articles

Tanshinone IIA Against Cerebral Ischemic Stroke and Ischemia-Reperfusion Injury: A Review of the Current Documents.

Stroke is a well-known neurological disorder that carries significant morbidity and mortality rates worldwide. Cerebral Ischemic Stroke (CIS), the most common subtype of stroke, occurs when thrombosis or emboli form elsewhere in the body and travel to the brain, leading to reduced blood perfusion. Cerebral Ischemia/Reperfusion Injury (CIRI) is a common complication of CIS and arises when blood flow is rapidly restored to the brain tissue after a period of ischemia. The therapeutic approaches currently recognized for CIS, such as thrombolysis and thrombectomy, have notable side effects that limit their clinical application. Recently, there has been growing interest among researchers in exploring the potential of herbal agents for treating various disorders and malignancies. One such herbal agent with medicinal applications is tanshinone IIA, an active diterpene quinone extracted from Salvia miltiorrhiza Bunge. Tanshinone IIA has shown several pharmacological benefits, including anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective properties. Multiple studies have indicated the protective role of tanshinone IIA in CIS and CIRI. This literature review aims to summarize the current findings regarding the molecular mechanisms through which this herbal compound improves CIS and CIRI.

Clinicodemographic and Dermoscopic Features of Basal Cell Carcinoma among Filipino Patients Seen in a Tertiary Care Clinic.

Dermoscopy enhances detection of basal cell carcinoma (BCC), especially for the pigmented subtype common among Asians. However, there is limited data on dermoscopic features of BCC in Filipinos. The objective of this study is to describe the clinicopathologic profile and dermoscopic features of BCC in Filipinos seen in a tertiary care clinic. A cross-sectional study was conducted in the Philippines from November 2019 to December 2021 in a tertiary care clinic. Fifty-three (53) lesions suspicious for BCC were analyzed using dermoscopy prior to histologic confirmation. Fifty (50) biopsy-proven BCC lesions were included in the analysis. Lesions were more commonly seen in females (72.50%), and located on the head and neck (88%). The most common histopathologic subtype was nodular (74%). The most common dermoscopic features were large blue-gray ovoid nests (86%) and ulcerations (70%). The most common BCC type among the study participants was nodular, with large blue-gray ovoid nests and ulceration seen on dermoscopy.

NT-proBNP levels in patients with primary hyperaldosteronism and autonomous cortisol cosecretion.

Patients with primary aldosteronism (PA) have higher cardiac comorbidities including more pronounced left ventricular hypertrophy than patients with essential hypertension. Autonomous cortisol cosecretion (ACS) is a common subtype in PA associated with a worse metabolic profile. Autonomous cortisol cosecretion may affect myocardial parameters and result in a worse cardiac outcome compared to patients with PA and without ACS. Three hundred and sixty-seven patients with PA undergoing 1 mg dexamethasone suppression test (DST) and echocardiography at baseline from 2 centers of the German Conn's Registry were included. Follow-up for up to 3.8 years was available in 192 patients. Patients with PA and ACS had higher NT-proBNP levels at baseline compared to patients with PA without ACS (114 vs 75.6 pg/mL, P = .02), but showed no difference in echocardiography values. NT-proBNP levels showed a significant positive correlation (r = 0.141, P = .011) with cortisol levels after DST at baseline. In response to therapy of PA, NT-proBNP levels decreased, but remained significantly higher in patients with ACS compared to patients without ACS. At follow-up, left ventricle end-diastolic dimension (LVEDD) decreased significantly only in patients without ACS. Left atrial diameter (LAD) decreased significantly in patients without ACS and in female patients with ACS but not in male patients. Left ventricular mass index (LVMI) significantly improved in female patients without ACS but remained unchanged in female patients with ACS as well as in male patients at follow-up. In patients with PA, concomitant ACS is associated with a worse cardiac profile and only partial recovery even years after initiation of targeted PA therapy.

The Effect of Surgical Resection on Cancer-Specific Mortality in Pelvic Soft Tissue Sarcoma According to Histologic Subtype and Stage

Background/Objectives: The impact of surgical resection versus non-resection on cancer-specific mortality (CSM) in soft tissue pelvic sarcoma remains largely unclear, particularly when considering histologic subtypes such as liposarcoma, leiomyosarcoma, and sarcoma NOS. The objective of the present study was to first report data regarding the association between surgical resection status and CSM in soft tissue pelvic sarcoma. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019, we identified 2491 patients diagnosed with pelvic soft tissue sarcoma. Cumulative incidence plots were used to illustrate CSM and other-cause mortality rates based on the histologic subtype and surgical resection status. Competing risk regression models were employed to assess whether surgical resection was an independent predictor of CSM in both non-metastatic and metastatic patients. Results: Among the 2491 patients with soft tissue pelvic sarcoma, liposarcoma was the most common subtype (41%), followed by leiomyosarcoma (39%) and sarcoma NOS (20%). Surgical resection rates were 92% for liposarcoma, 91% for leiomyosarcoma, and 58% for sarcoma NOS in non-metastatic patients, while for metastatic patients, the rates were 55%, 49%, and 23%, respectively. In non-metastatic patients who underwent surgical resection, five-year CSM rates by histologic subtype were 10% for liposarcoma, 32% for leiomyosarcoma, and 27% for sarcoma NOS. The multivariable competing risk regression analysis showed that surgical resection provided a protective effect across all histologic subtypes in non-metastatic patients (liposarcoma HR: 0.2, leiomyosarcoma HR: 0.5, sarcoma NOS HR: 0.4). In metastatic patients, surgical resection had a protective effect for those with leiomyosarcoma (HR: 0.6) but not for those with sarcoma NOS. An analysis for metastatic liposarcoma was not possible due to insufficient data. Conclusions: In non-metastatic soft tissue pelvic sarcoma, surgical resection may be linked to a reduction in CSM. However, in metastatic patients, this protective effect appears to be limited primarily to those with leiomyosarcoma.

WIMOAD: Weighted Integration of Multi-Omics data for Alzheimer's Disease (AD) Diagnosis.

As the most common subtype of dementia, Alzheimer's disease (AD) is characterized by a progressive decline in cognitive functions, especially in memory, thinking, and reasoning ability. Early diagnosis and interventions enable the implementation of measures to reduce or slow further regression of the disease, preventing individuals from severe brain function decline. The current framework of AD diagnosis depends on A/T/(N) biomarkers detection from cerebrospinal fluid or brain imaging data, which is invasive and expensive during the data acquisition process. Moreover, the pathophysiological changes of AD accumulate in amino acids, metabolism, neuroinflammation, etc., resulting in heterogeneity in newly registered patients. Recently, next generation sequencing (NGS) technologies have found to be a non-invasive, efficient and less-costly alternative on AD screening. However, most of existing studies rely on single omics only. To address these concerns, we introduce WIMOAD, a weighted integration of multi-omics data for AD diagnosis. WIMOAD synergistically leverages specialized classifiers for patients' paired gene expression and methylation data for multi-stage classification. The resulting scores were then stacked with MLP-based meta-models for performance improvement. The prediction results of two distinct meta-models were integrated with optimized weights for the final decision-making of the model, providing higher performance than using single omics only. Remarkably, WIMOAD achieves significantly higher performance than using single omics alone in the classification tasks. The model's overall performance also outperformed most existing approaches, highlighting its ability to effectively discern intricate patterns in multi-omics data and their correlations with clinical diagnosis results. In addition, WIMOAD also stands out as a biologically interpretable model by leveraging the SHapley Additive exPlanations (SHAP) to elucidate the contributions of each gene from each omics to the model output. We believe WIMOAD is a very promising tool for accurate AD diagnosis and effective biomarker discovery across different progression stages, which eventually will have consequential impacts on early treatment intervention and personalized therapy design on AD.

Head and neck sarcomas: Thirty years of experience in a tertiary referral center in Brazil.

This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil. HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors. A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence. In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.

Oncological outcomes and risk factors for recurrence of mucinous borderline ovarian tumors: A 15-year experience at a tertiary center.

The most common subtype of borderline ovarian tumors in Asia is mucinous borderline ovarian tumors (mBOTs). Intraoperative distinction from mucinous carcinoma can be difficult. Despite the indolent behavior of mBOTs, recurrence or metastases may occur. The objectives of this study were to determine the oncological outcomes of mBOTs and the risk factors for their recurrence. This retrospective study enrolled patients with mBOTs treated or referred to our institution between January 2005 and December 2019. Histological reviews of the recurrent cases (primary and recurrent or metastatic tumors) were performed. Patients with other tumor subtypes, pseudomyxoma peritonei, or no in-house operation were excluded. Two hundred thirty-two patients were diagnosed with mBOTs. The median follow-up was 52 months. Six patients (2.58%) had tumor recurrence or metastasis. The risk factors for recurrence were a ruptured tumor, residual tumor after an operation, high serum CA19-9 level, and stage of the disease. The recurrence rates of fertility-sparing and radical surgery were not significantly different. Detailed surgical staging, intraepithelial carcinoma, and microinvasion were also not associated with disease recurrence. mBOTs have an excellent prognosis. Currently, fertility-sparing surgery is the standard treatment, showing no significant difference in oncological outcomes compared to radical surgery. Patients with risk factors should be closely monitored.

Decreased PU.1 expression in mature B cells induces lymphomagenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells invivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function invivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development.

Epidemiology and Functional Outcome of Acute Stroke Patients in Korea using Nationwide data.

Korea's healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. 86,568 acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016 to 2021, focusing on acute subarachnoid hemorrhage, acute intracerebral hemorrhage, and acute ischemic stroke. Of these 86,568 patients, 8.3% was subarachnoid hemorrhage, 16.3% intracerebral hemorrhage, and 74.9% ischemic stroke. Trends showed decreasing subarachnoid hemorrhage and increasing intracerebral hemorrhage cases over the years. 68.3% stroke patients had the clear onset time. 49.6 % stroke patients arrived within 4.5 hours of symptom onset, with more treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of subarachnoid hemorrhage patients, 34.6% of intracerebral hemorrhage patients, and 63.8% of ischemic stroke patients. The results showed that ischemic stroke was the most common subtype, followed by intracerebral hemorrhage and subarachnoid hemorrhage. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and subarachnoid hemorrhage compared to intracerebral hemorrhage.

Characteristics, efficacy, and prognosis analysis of newly diagnosed marginal zone lymphoma.

To retrospectively analyze the characteristics of newly diagnosed marginal zone lymphoma (MZL) patients, evaluate the efficacy of different treatment regimens, and explore prognostic factors in the era of immunotherapy. We reviewed the clinical data of newly diagnosed MZL patients treated at the Department of Hematology, The First Hospital of Jilin University, from October 2013 to October 2023. Survival differences between groups were analyzed using the log-rank test, and prognostic factors were identified. A total of 265 newly diagnosed MZL patients were included, with a median age of 59 years (range 22-90). The most common pathological type was mucosa-associated lymphoid tissue (MALT) lymphoma, accounting for 66.0% of cases. Among the 147 MZL patients included in the efficacy analysis, the median follow-up was 43.4 months. Both the median progression-free survival (PFS) and overall survival (OS) were not reached. The 5-year PFS and OS rates were 76.0% and 86.6%, respectively. Patients who achieved complete response (CR) after induction therapy had significantly better PFS (P=0.0045), OS (P<0.001), and time to next treatment (TTNT) (P=0.0045) compared to those who did not achieve CR. A subgroup analysis was conducted on 51 MZL patients with high tumor burden who received ≥4 cycles of treatment. It was found that the CR rate (CRR) in patients receiving obinutuzumab (G) ± chemotherapy was significantly higher than in those receiving rituximab (R) ± chemotherapy (93.8% vs. 48.6%, P=0.002). Multivariate analysis revealed that disease progression or death within 24 months of initial treatment (POD24) was an independent risk factor affecting OS (P<0.001). Patients who experienced POD24 had a median survival of only 19.7 months, with a 3-year OS rate of just 37.6%, whereas those without POD24 had a 3-year OS rate of 97.3%. MZL is predominantly seen in middle-aged and elderly patients and is a specific indolent B-cell lymphoma, with MALT lymphoma being the most common subtype. Achieving CR after induction therapy significantly prolongs survival in MZL patients. Compared to R ± chemotherapy, G ± chemotherapy achieves a higher CRR in high tumor burden MZL patients. In the era of immunotherapy, POD24 is an independent prognostic factor for MZL.

Abstract C039: Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study

Abstract Background: Associations of nativity and breast cancer (BC) mortality are mixed in studies using cancer registry data. We examined associations in diverse women with detailed individual-level data on BC treatment and subtype. Methods: The study population included 5,718 Asian (n=722, 71% foreign-born), Hispanic (n=631, 42% foreign-born), and non-Hispanic White (n=4,365, 9% foreign-born) women from the ENCLAVE Study diagnosed with invasive BC from 1996-2013 using pooled, harmonized data from two (of three) cohorts with data on BC subtype. Data on nativity, reproductive and behavioral factors were self-reported from questionnaires; data on disease severity, BC subtype (luminal A, luminal B, Her2 expressing, triple negative breast cancer), treatment, and mortality were obtained from cancer registries and electronic health records. Recurrences were identified by recurrence algorithms and medical record review. We fit Cox proportional hazards regression models to examine associations between self-reported nativity and recurrence, BC-specific mortality, and overall mortality. Covariates included age, sociodemographic factors, disease severity, and treatment, reproductive and behavioral factors. We also examined associations by race, ethnicity, and BC subtype. Results: Compared to US-born women, foreign-born women had lower total mortality (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.64-0.89); lower risks were suggested for recurrence (HR=0.85, 95% CI: 0.68-1.06) and breast cancer-specific mortality (HR=0.87, 95% CI: 0.66-1.14). Stratified by BC subtype, foreign- (vs. US-) born women had a lower risk of overall mortality among those with luminal A (HR=0.72, 95% CI: 0.56-0.92) and luminal B (HR=0.66, 95% CI: 0.48-0.91) but not other subtypes. Among women with luminal B BC, these associations reached statistical significance for recurrence (HR=0.65, 95% CI: 0.45-0.94) and BC-specific mortality (HR=0.53, 95% CI: 0.33-0.84). We noted no associations in other BC subtypes though analyses of less common subtypes were underpowered. Associations did not differ by race or ethnicity. Conclusion: Foreign-born women with BC had lower risk of overall mortality than US-born women. Risks of recurrence and BC-specific mortality were lower in foreign-born vs. US-born women among those with the luminal B BC subtype. Associations were not explained by behavioral or reproductive factors. Citation Format: Candyce Kroenke, Rhonda Aoki, Stacey Alexeeff, Scarlett Gomez, Bette Caan, Brittany Morey, Jacqueline Torres, Larry Kushi. Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C039.

Prognostic analysis of Pneumocystis jirovecii pneumonia in patients with systemic vasculitides: a retrospective cohort study

ObjectivesPneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors.MethodData on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared.ResultsAmong 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD.ConclusionsMPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.Key Points• Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients.• Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis.• In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.

Abstract C171: Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities

Abstract Lung cancer remains the leading cause of cancer-related mortality globally and continues to contribute significantly to cancer health disparities. Black/African American (B/AA) men exhibit a higher risk of lung cancer compared to White men; B/AA individuals also exhibit lower 5-year survival and stage-specific survival rates than White subjects. Biological factors, including genetic differences in cancer driver mutation, may influence this disparity. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer across all ethnic groups, including B/AA individuals. Our study aims to characterize the main driver and co-mutation signatures of LUAD in B/AA individuals, who are significantly underrepresented in current mutational studies. We hypothesize that B/AA individuals will have a unique repertoire of cancer driver genes, which could contribute to genetic differences and response to targeted therapies compared to LUAD of White subjects. We are obtaining 100 de-identified archival formalin-fixed, paraffin-embedded (FFPE) LUAD samples from B/AA subjects from cancer registries in Florida and California. Extraction of DNA from the FFPE samples is in progress, and samples have been sent for whole exome sequencing (WES) and ancestry determination. This data will then be analyzed and compared with known LUAD mutation profiles from other ethnicities. Identification of cancer driver mutations will then inform the development of in vitro models for therapeutic testing. To date, the limited information on cancer driver genes in LUAD from B/AA subjects suggests that KRAS is the most common cancer driver gene, just like in LUAD from White subjects, and is found in ∼34% of cases. Therefore, we anticipate identifying KRAS mutations similar to this proportion based on the collection of previously published literature analyses. One key goal of this study is to obtain more information about the exact spectrum of KRAS mutations in LUAD from B/AA subjects. In addition, our work may unveil new variants of known cancer driver mutations such as KRAS, EGFR, BRAF, etc., and finally, “new” driver genes. Our efforts will address critical gaps in the understanding of lung cancer driver genes, a key step to developing personalized treatment of lung cancer and mitigating cancer health disparities between B/AA and White individuals. Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI), the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI, and by the Undergraduate Research Associates Program supported by the USC Provost. Citation Format: Davin Pan, Daniel J. Mullen, Colton Stensrud, Jose Aparicio, Christina M. Gobin, Sofia Lugo, Kweku Ofosu-Asante, Justin K. Mensah-Mamfo, Kyle R Phillips, Yong Huang, Nazarius S. Lamango, William D Wallace, Suhn K Rhie, Kristinanna M. Fredenburg, Ite A. Offringa. Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C171.

Abstract C168: Developing lung adenocarcinoma cell lines to mitigate lung cancer health disparities

Abstract Lung cancer continues to be the number one cause of cancer-related deaths worldwide and remains a prominent source of cancer health disparities. Black/African American (B/AA) males exhibit a 12% higher lung cancer incidence rate and a 15% higher lung cancer death rate when compared to white males. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer in all ethnic/racial groups, including B/AAs. To further examine this phenomenon, we want to create a collection of lung cancer cell lines that would be useful for molecular studies of lung cancer development, progression, development of new targeted therapies, and pre-clinical drug testing. After reviewing the literature (Leon et al. 2023, Frontiers in Oncology, Vol. 13, p. 1187585, 2023), we identified only 30 unique B/AA cell lines out of ∼800, the majority of which are derived from White and Asian patients. Moreover, only 6 of the 30 cell lines are derived from patients with LUAD. We are in the process of deriving more LUAD cell lines from B/AA patients as well as alveolar epithelial cell lines in order to study the development of LUAD. In addition, we are creating a collection of multiple independent isogenic cell line variants from an existing lung cancer cell line NCI-H23. NCI-H23 was derived from a B/AA male LUAD patient and harbors a KRASG12C heterozygous mutation. G12C is the most common KRAS mutation in LUAD (∼40% of KRAS mutations) followed by G12V (∼20%), G12D (∼15%), G12A (∼10%), and G13C (∼6%). We used CRISPR/Cas-9 genome- based editing to replace the KRASG12C mutation with KRASG12V, KRASG12D, KRASG12A, and KRASG13C. We have derived multiple independent cell lines for most mutations. We are in the process of performing whole genome sequencing of these cell lines to exclude any off-target effects that may have arisen from the CRISPR/Cas-9 engineering. In addition, we will carry out whole genome RNA sequencing to assess the effect of the engineering and/or KRAS mutation switching. As a control, we are also sequencing the genomes and transcriptomes of three monoclonal cell lines we derived from NCI-H23 cells, to determine what variability ensues with the derivation of monoclonal lines, since that is required to obtain the CRISPR/Cas9-edited cells. We will use this collection of cell lines to study the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs) and other drugs on cell lines bearing these KRAS mutations. PCAIs were developed to target cells carrying mutant KRAS. Our efforts will provide new cell lines to study lung adenocarcinoma in B/AA subjects, addressing a key shortcoming and disparity in the lung cancer research toolkit. Citation Format: Sofia A. Lugo, Christopher Leon, Matthew A. Gladstone, Chunli Yan, Daniel J. Mullen, Pablo E. Puente, Kweku Ofosu-Asante, Justin K. Mensah-Mamfo, Kyle R. Phillips, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Developing lung adenocarcinoma cell lines to mitigate lung cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C168.

Analysis of HIV-1 Subtypes and Transmitted Drug Resistance in Hospitalized Treatment-Native Patients With AIDS

To investigate the distribution characteristics of HIV-1 subtypes, the status of transmitted drug resistance (TDR), and the influencing factors of TDR in treatment-naive patients with AIDS who are hospitalized. Treatment-naive patients with AIDS who were admitted to the Infectious Disease Department, Public Health Clinical Center of Chengdu between January 2020 and December 2022 were enrolled in the study. The diagnosis and confirmation diagnosis of all the subjects were made at the same hospital. Blood samples were collected from the subjects before antiretroviral therapy (ART). The in-house method was used for HIV gene amplification and sequencing. A phylogenetic tree was constructed to analyze the HIV-1 subtypes. The Stanford HIV Drug Resistance Database was used to conduct an online comparative analysis of the drug resistance mutation sites and to determine the types and levels of drug resistance. The distribution characteristics of HIV-1 subtypes, the occurrence of TDR, and the influencing factors of TDR were analyzed. A total of 213 patients were included in the study and their blood samples were collected. HIV-1 subtypes were successfully amplified in 83.10% (177/213) of the subjects. Ten HIV subtypes were identified, with CRF07_BC being the most common subtypes, accounting for 43.50% (77/177), which was followed by CRF01_AE at 37.85%. Unique recombinant forms (URFs) were relatively uncommon, accounting for 8.47%. The other subtypes accounted for 10.17%. These 4 categories of HIV-1 subtypes were distributed with statistically significant differences in different age groups (P=0.024). Further analysis revealed significant differences in the distribution of the HIV-1 subtypes of CRF01_AE and URFs between the groups of patients aged 30-50 years and those over 50. In addition, URFs accounted for a higher proportion in patients aged 30 to 50 years (P=0.008). The incidences of TDR were 6.49%, 8.96%, 13.33%, and 5.56% for CRF07_BC, CRF01_AE, URFs, and other subtypes, respectively, showing no significant difference (P>0.05). The overall TDR was 6.57%. The TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 5.16%, and the main mutation sites were V179D/E, E138A/G, V106M/I, and Y181C. The TDR for nucleoside reverse transcriptase inhibitors (NRTIs) was 1.88%, and the main mutation site was M184V. One patient was found to be resistant to both NNRTIs and NRTIs. The highly resistant rate was 4.23%, moderate resistance was 0.47%, and low resistance was 1.88%. No significant effects of the specific years, demographic characteristics, transmission route, baseline condition, and opportunistic infections on TDR were found in this study (P>0.05). The HIV-1 subtypes are diverse and complex in treatment-naive patients with AIDS who were hospitalized. The overall prevalence of TDR is relatively high. It is necessary to strengthen HIV drug resistance testing to optimize ART treatment and reduce the risk of drug resistance transmission.

Sinonasal intestinal-type adenocarcinoma in northern Portugal: a woodworker’s occupational hazard

Abstract Background Sinonasal carcinomas (SNC) constitute about 3% of all head and neck carcinomas, squamous cell carcinoma being the most common histologic subtype. Some geographical patterns in incidence are observed, as occupational exposure to wood dust is associated with intestinal-type adenocarcinoma (ITAC). Aims This study aims to describe the prevalence and characteristics of sinonasal ITAC cases in a region of northern Portugal with a robust wood industry. Methods A retrospective study of all sinonasal malignancies diagnosed over 5 years, in a tertiary hospital, primarily focused on ITAC subtypes. Data on sociodemographic and clinical variables were collected through electronic medical records and telephonic assessments. Results Of all 33 cases, 85% were ITAC. ITAC predominantly affected males (96%) with a mean age of 66.2 years. Most patients diagnosed with sinonasal ITAC had occupational wood dust exposure (96%), particularly to hardwoods. Initial symptoms included unilateral nasal obstruction (75%) and epistaxis (71%). Despite a median time of 3 months from symptoms to consultation, 50% presented at an advanced stage, with a 29% mortality rate. Conclusions Sinonasal ITAC is an occupational hazard of woodworkers and represents the vast majority of SNC in the region. This study advocates for targeted community interventions, emphasizing occupational safety measures and healthcare awareness to reduce morbimortality associated with this occupational cancer.

A mini-update on chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses and the nasal cavity lasting longer than 12 weeks. This disease is a common clinical syndrome with significant monetary burden due to the high costs of medical visits, diagnostic tests, medications, and surgical therapies. CRS without nasal polyposis (CRSsNP) is the most common subtype of CRS, accounting for about 70% of all patients. Other subtypes include CRS with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). CRSwNP has the worldwide prevalence of 2% to 4% and is often accompanied by type 2 inflammation and asthma as a comorbid condition. Pediatric chronic sinusitis is distinct from adult chronic sinusitis and is currently considered an infectious process, characterized by persistent inflammation representing an exaggerated immune response to an external stimulus. The medical and surgical management of CRS has been remarkably modified in the past two decades. The aim of this study was to present an update on CRS based on the recent years’ literature.

Acute Myeloid Leukemia among Patients attending Sana’a Hospitals, Yemen: Prevalence, Subtypes and Hematological Patterns

Objectives: Acute myeloid leukemia (AML) is malignant disorder of cells of myeloid lineage in the bone marrow due to chromosomal abnormalities, leading to accumulation of myeloblasts in the bone marrow and infiltration to peripheral tissues. The aim of this study was to determine the prevalence, subtypes and hematological patterns of AML among patients attending Sana’a hospitals, Yemen. Materials and methods: This cross-sectional study was carried out on total 257 patients with hematological malignancies (HMs) during the period from November 1, 2023 to March 31, 2024. Among HMs, there were 79 patients diagnosed with AML by complete blood count (CBC), by Giemsa stained blood/BM films, and by immunophenotyping using flow cytometry. Data was analyzed using SPSS-26. Results: Among 257 patients with HMs, AML was found in 79 patients with prevalence of 30.7%. AML patients included 53 (67.1%) males and 26 (32.9%) females., with M:F ratio of 2:1 and aged between 4 and 80 years, FAB-M2 was the most common subtype of AML in 30 (37.97%) of patients; among them, there were 19 (24.05%) males and 11 (13.92%) females, the M:F ratio is 1.7:1. FAB-M2 was followed by M1 (26.58), M5 (17.2), M3 (7.59), M4 (5.06), M0 (3.8) and M7 (1.26). The hematological patterns included decreased Hb, increased WBC and decreased platelets in 97.5%, 82.3% and 96.2% of patients, respectively. Conclusion: Leukemia was the most prevalent type among hematological malignancies. The prevalence of AML was high and represent the second leukemia type. AML-M2 was the common subtype of AML.

An Oral Botanical Supplement Improves Small Intestinal Bacterial Overgrowth (SIBO) and Facial Redness: Results of an Open-Label Clinical Study.

Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

The Landscape of Breast Cancer Molecular and Histologic Subtypes in Canada.

Purpose: To characterize the histologic and molecular subtype distribution of, and survival from, breast cancer (BC) among Canadian women overall, and by stage and age at diagnosis. Methods: Invasive BC cases from the Canadian Cancer Registry for women aged 15-99 years between 2012 and 2017 in Canada, excluding Quebec, were examined using pre-existing mortality linkages. Stage at diagnosis, molecular, and histologic subtypes, and 5-year net survival (NS) by age, subtype, and stage were determined. Results: 107,271 women with BC were included. Luminal A was the most common subtype, present in increasing proportions as women aged, up to a maximum of 55% of cases in 70-74. Ductal and luminal A were most likely to be diagnosed at stage I, while HER2+ had the highest proportion of diagnosis at stage III; triple negative (TN) and unknown had the highest proportion of stage IV. For all stages combined, luminal A had a five-year NS of 98%, while TN was 74%. NS for stage I BC was 99-100% for all subtypes, excepting TN, which was 96%. Survival decreased with advancing stage, most markedly for TN, for which stage III was 47% and stage IV 7%. Survival by equivalent stage and subtype was comparable across age groups but declined in older age categories. Conclusions: The varying natural histories of BC subtypes and histologies can inform prognoses, health system economics, and screening practices. The NS of 96% or greater for stage I, regardless of subtype, highlights the importance of early detection for all subtypes of BC, especially in aggressive subtypes.