Surgical Resection Of Tumor Research Articles

Epigenetic regulation of SST2 expression in small intestinal neuroendocrine tumors.

Somatostatin receptor type 2 (SST2) expression is critical for the diagnosis and treatment of neuroendocrine tumors and is associated with improved patient survival. Recent data suggest that epigenetic changes such as DNA methylation and histone modifications play an important role in regulating SST2 expression and tumorigenesis of NETs. However, there are limited data on the association between epigenetic marks and SST2 expression in small intestinal neuroendocrine tumors (SI-NETs). Tissue samples from 16 patients diagnosed with SI-NETs and undergoing surgical resection of the primary tumor at Erasmus MC Rotterdam were analysed for SST2 expression levels and epigenetic marks surrounding the SST2 promoter region, i.e. DNA methylation and histone modifications H3K27me3 and H3K9ac. As a control, 13 normal SI-tissue samples were included. The SI-NET samples had high SST2 protein and mRNA expression levels; a median (IQR) of 80% (70-95) SST2-positive cells and 8.2 times elevated SST2 mRNA expression level compared to normal SI-tissue (p=0.0042). In comparison to normal SI-tissue, DNA methylation levels and H3K27me3 levels were significantly lower at five out of the eight targeted CpG positions and at two out of the three examined locations within the SST2 gene promoter region of the SI-NET samples, respectively. No differences in the level of activating histone mark H3K9ac were observed between matched samples. While no correlation was found between histone modification marks and SST2 expression, SST2 mRNA expression levels correlated negatively with DNA methylation within the SST2 promoter region in both normal SI-tissue and SI-NETs (p=0.006 and p=0.04, respectively). SI-NETs have lower SST2 promoter methylation levels and lower H3K27me3 methylation levels compared to normal SI-tissue. Moreover, in contrast to the absence of a correlation with SST2 protein expression levels, significant negative correlations were found between SST2 mRNA expression level and the mean level of DNA methylation within the SST2 promoter region in both normal SI-tissue and SI-NET tissue. These results indicate that DNA methylation might be involved in regulating SST2 expression. However, the role of histone modifications in SI-NETs remains elusive.

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Association of Various Factors in Terms of Pathological Response in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Objective: To analyze the association of various factors in terms of pathological response among breast cancer patients.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Oncology Department, Combined Military Hospital, Rawalpindi Pakistan, from Jan 2019 to Jun 2020.
 Methodology: This study was conducted on 82 female patients with advanced breast cancer who required neo-adjuvant chemotherapy followed by surgical tumour resection. The pathological response was classed as complete, partial, and no response based on histological findings on resected tumour sample. In addition, the age of the patient, stage of disease at presentation, intrinsic (molecular) subtypes and pathological subtype were the factors correlated with response to treatment in the target population.
 Results: A total of 82 female patients were included in the final analysis. The mean age of the patients was 47.421±8.857 years. 27(32.9%) had a complete pathological response, 34(41.5%) had partial, and 21(25.6%) had no response to the neoadjuvant therapy. Intrinsic subtypes of the tumour were statistically significantly associated with pathological response to neoadjuvant therapy (p-value<0.05) in our study participants.
 Conclusion: Considerable number of patients with advanced breast cancer showed pathological responses to neoadjuvant chemotherapy. In addition, intrinsic subtyping significantly predicted pathological response to therapy in our patients, with triple-negative patients having more chances of complete response to neoadjuvant chemotherapy.

Acidic tumor microenvironment-activatable fluorescent diagnostic probe for the rapid identification and resection of human tumors via spraying

A fluorescent diagnostic probe for real-time intraoperative image-guided tumor resection can significantly improve the efficiency and quality of oncological therapy, but their development is challenging. Herein, a novel fluorescent diagnostic probe called HLTC based on β-carboline was designed and synthesized. HLTC was found to show a ∼10-fold enhancement of fluorescence quantum field with pH from 7.4 to 4.0, indicating its imaging potential in acid environment which is a typical hallmark of the tumor microenvironment (TME). Following fluorescence microscopy imaging showed HLTC could emit specific signals in cancer cells and sections, by both one-photon excitation and two-photon excitation. Importantly, HLTC enabled the precise and rapid delineation of both transplanted tumor and clinical tumor tissues within several minutes of simple topical spray. The tumor-to-background ratio (TBR) was up to 10.2 ± 1.0 at clinical liver cancer tissues and 9.9 ± 0.3 at clinical colon cancer tissues, allowing precise tumor margin identification and the effective guidance of surgical tumor resection. Furthermore, CCK8 assay, pharmacokinetic evaluation, blood analysis and H&E staining were performed, which verified high biocompatibility and biosafety of HLTC at working concentration. These results reveal the exciting potential of this small-molecule fluorescent diagnostic probe for real-time fluorescence-based navigation during surgical tumor resection.

Identification of KRAS mutation and HER2 expression in Indonesian colorectal cancer population: a cross-sectional study.

This research is a cross-sectional study. The research subjects in this study were colorectal cancer patients in the digestive surgery division. There were 58 study subjects. Examination of KRAS mutations was carried out by PCR on fresh tumor tissue obtained from surgery or colonoscopy. Meanwhile, the HER2 examination used the immunohistochemistry method of paraffin blocks for anatomical pathology examination. Examination of KRAS mutations showed 28/58 (43.8%) patients with colorectal cancer, while HER2 overexpression was found in 6/58 (10.3%) patients with colorectal cancer. Univariate analysis of KRAS mutations and HER2 expression showed that four subjects with KRAS mutations had excess HER2 expression (P=0.341). There is no association between KRAS mutations and HER2 overexpression in colorectal cancer patients.

Abstract #1401779: Rare Case of Functional Gonadotroph Adenoma

Of all pituitary adenomas, approximately 25-35% are clinically nonfunctioning or "silent" and of those approximately 70-90% are gonadotropin adenomas making them the most common nonfunctional pituitary macroadenoma. However, it is important to know that gonadotropin adenomas can be functional and that gonadotropin excess can result in clinical symptoms and lab abnormalities. This case demonstrates an example of a functional gonadotropin pituitary adenoma overproducing FSH resulting in high-normal testosterone level in addition to compressive symptoms of the optic chiasm. 57-year-old African-American male with pre-diabetes mellitus and gout (only home meds are allopurinoL 300 MG once daily and indomethacin 50 MG three times daily) presented for evaluation of vision loss and large sellar mass on MRI. Vision loss first noted January 2022 along with occasional headaches for 3-4 months (no headaches prior). Patient eventually saw a neuro-ophthalmologist for visual field testing demonstrating left field deficits concerning for optic nerve compression. He then underwent orbital MRI which demonstrated a large sellar mass extending into bilateral cavernous sinus and effacing and displacing the optic chiasm. During visit, patient admitted to fatigue, constipation, polyuria, and nocturia. He denied‌ breast tenderness, nipple discharge, weight change, temp intolerance, skin/hair change, palpitations, tremors, increase hand/foot size, teeth spacing change, worse glycemic control, hypertension, joint pain, acne, hirsutism, striae, clotting disorders, fractures, decreased libido, or erectile dysfunction. He had no known allergies. Blood pressure109/83 | Pulse 101 | Ht 5' 10" (1.778 m) | Wt 88.2 kg (194 lb 7.1 oz) | SpO2 97% | BMI 27.90 kg/m2. Physical exam: Visual fields intact to confrontation but with some patchy deficits in the left eye only. No other notable findings. Subsequent labs demonstrated appropriate cortisol 11.8 ng/dL with normal ACTH of 17 pg/mL, normal IGF-1 of 95 ng/mL, normal TSH of 1.6 uIU/mL with normal free T4 of 0.8 ng/dL. However, prolactin was mildly elevated at 36.5 ng/mL (presumably from stalk effect given size of tumor) and FSH was impressively elevated at 70.3 mIU/mL with a normal LH of 6.5 mIU/mL and a high-normal total testosterone level of 890 ng/dL which was highly suggestive an FSH-producing functional gonadotropin adenoma. It is important to realize the efficacy of surgical resection of functional non-prolactinoma pituitary tumors, especially when the optic chiasm is involved. Patient underwent transsphenoidal resection of pituitary adenoma and indeed pathology revealed a gonadotroph adenoma with SF1 and alpha subunit. He reported slightly improved vision in left eye and had some residual occasional headaches. Awaiting post-operative labs but anticipate normalization of prolactin and FSH and a likely decrease in testosterone level. Awaiting post-operative visual field testing to demonstrate objective improvement. These should be available by the time of the conference.

Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU+DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release invitro and invivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU+DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU+DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.

Surgical resection of primary tumors improves survival in patients with lung metastases: a population-based SEER analysis.

The lung is a common site for cancer metastasis. Some cancer patients would develop lung metastases throughout the course of their illness. However, choosing surgical resection of the primary tumor (SRPT) or palliative treatment in patients with lung metastases remains controversial. Lung metastatic patients diagnosed from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients were divided into two subgroups (surgery and non-surgery). Further, all the 58 tumor types were classified into 13 subtypes. The clinical and demographic features were examined by the Fisher's exact test, chi-squared test, or z-test. Overall survival (OS) was analyzed using the Kaplan-Meier (K-M) estimator and a log-rank test for each primary tumor type. Multivariable survival analyses of OS were performed using the Cox proportional hazards model. Among the 118,088 patients selected for study, 18,688 (15.83%) patients had undergone surgery. The analyses demonstrated that there was a significant association between SRPT and better OS in patients with lung metastases. The median survival time increased from 4.0 months in the non-surgery group to 19.0 months in the surgery group. Multivariate Cox regression analyses further validated that patients who underwent SRPT had an improved OS. The current study demonstrated that patients with lung metastases can benefit from SRPT. SRPT should be considered in patients with lung metastases. Properly designed prospective randomized clinical trials would be required to further verify the conclusion.

Pre-Operative Embolisation In Surgical Carotid Body Tumour Resection: Is It Really Useful?

Objective: Carotid body tumour (CBT) is the most common tumour in the family of head and neck paragangliomas, making up approximately 60 – 70% of them. They are typically diagnosed in the fourth to fifth decades with a female predilection. CBT present as soft tissue density on non-contrast CT and complete transfemoral angiography is considered the “gold standard” when establishing diagnosis of CBT with a 100% accuracy. Primary treatment consists of surgical resection to reduce tumour mass size and to decrease surgical risks associated with resection of these highly vascularised tumours, pre-operative embolisation of CBT has been proposed in the literature with varying results. There are no universal guidelines regarding pre-operative CBT embolisation and performance is mostly guided by preference of the surgeon and tumour size. The decision to perform pre-operative embolisation, usually 24 – 48 hours before surgery (though timing of surgical CBT resection following prior embolisation varies between 1 and 14 days post embolisation), is largely dependent on tumour size. Embolisation can be done via a transfemoral arterial route, or percutaneous (direct intralesional) route. The aim of this study was to investigate the efficacy of pre-operative embolisation prior to surgical CBT resection regarding intra-operative blood loss, operative time, length of hospital stay, and peri-operative complications (e.g., transient or ischaemic cerebrovascular event, vascular injury, or cranial nerve injury).

Easier way of managing gastric gastrointestinal stromal tumor located at unusual site: a case report

Intraluminal gastric gastrointestinal stromal tumors (GISTs) located at the posterior wall and near the gastroesophageal (GE) junction represent a surgical challenge. We present a easier laparoscopic assisted mini laparotomy approach for resection of gastric GISTs of such location. A 42 years old female presented with history of Malena and anemia. Endoscopic and contrast enhaced computerised tomography (CECT) scan findings were suggestive of GIST arising from posterior wall along lesser curvature in proximal body of stomach. We planned her for surgical resection of tumor. During laparoscopy, posterior wall stomach was completely mobilised after dividing gastrocolic and phrenogastric ligaments. Due to unfavourable location of tumor in posterior wall and proximity to GE junction, accessibility for negative resection margin was difficult, so we did mini laparotomy (approx 5 cm midline incision) and already mobilised stomach is delivered out, wedge resection of tumor done after assuring resection margin with direct palpation. GISTs of the posterior wall and in close proximity to the GE junction can be safely resected with laparoscopic assistance using such an approach. This technique is useful alternative in unavailability of simultaneous laparoscopy with endoscopy as required in laparoscopic and endoscopic cooperative surgery in such locations of tumor.

Recurrent metastatic retroperitoneal dedifferentiated liposarcoma: a case report and literature review

BackgroundRetroperitoneal liposarcoma (RPLPS), a rare tumor, is often treated using surgical procedures as the first choice for treatment. However, there is no consensus on the scope of surgical resection. In addition, the treatment outcomes of conventional radiotherapy and chemotherapy have not been satisfactory, particularly for specific types of LPS, such as dedifferentiated LPS. In this case study, we present a brief review of other cases of RPLPS, highlighting the selection of surgical scope for RPLPS and related adjuvant treatment for advanced RPLPS.Case presentationA case study is reported regarding an extremely rare recurrent and metastatic retroperitoneal dedifferentiated LPS. The primary RPLPS tumor, with a diameter of 20 cm and a weight of 2.5 kg, occupied the whole left abdomen and adhered to the left kidney. A surgical tumor resection combined with a left nephrectomy is performed. During the 6th -month postoperative follow-up examination, we observed the local recurrence of the tumor in the operation area, in addition to multiple metastatic tumors in both lungs. Further, the prescribed 3-month targeted treatment with anlotinib significantly reduced the size of the metastatic pulmonary tumors. However, the recurrent retroperitoneal tumors showed no significant change in size. Eventually, we observed no substantial evidence of tumor progression, with the patient’s condition under control.ConclusionThe case demonstrated that the postoperative recurrence of widespread RPLPS required R0 resection to cure the disease, considering targeted therapy for advanced RPLPS control.

Volume-based 18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters correlate with delayed neck metastasis in clinical early-stage oral squamous cell carcinoma.

There is no known preoperative marker that can effectively predict the risk of delayed neck metastasis (DNM), which is an important factor that determines the prognosis of early-stage oral cancer. In this study, we examined whether 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) uptake parameters of primary cancer can predict the risk of DNM in early-stage oral squamous cell carcinoma (OSCC). Data from patients with stage I-II OSCC who underwent surgical resection of the primary tumor without elective neck dissection between January 2009 and December 2016 were retrospectively reviewed. Patient characteristics, histopathological factors, and PET/CT parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were evaluated for their association with DNM. DNM rates were calculated, and the parameters that were statistically significant in the univariate analysis were used as explanatory variables. Independent factors associated with DNM were identified using multivariate analysis. For all statistical analyses, p-values < 0.05 were considered statistically significant. Data from 71 patients were analyzed in the study. The overall DNM rate among all patients was 21.8%. The univariate analysis showed that the T classification, depth of invasion, pattern of invasion, lymphovascular invasion, SUVmax, MTV, and TLG were significant predictors of DNM. However, the multivariate analysis revealed that only the depth of invasion, MTV, and TLG were independent predictors of DNM. This study suggests that, in addition to conventional predictors, volume-based PET parameters are useful predictors of DNM in those with early-stage OSCC.

Improving outcomes in patients with oesophageal cancer

The care of patients with oesophageal cancer or of individuals who have an elevated risk of oesophageal cancer has changed dramatically. The epidemiology of squamous cell and adenocarcinoma of the oesophagus has diverged over the past several decades, with a marked increase in incidence only for oesophageal adenocarcinoma. Only in the past decade, however, have molecular features that distinguish these two forms of the disease been identified. This advance has the potential to improve screening for oesophageal cancers through the development of novel minimally invasive diagnostic technologies predicated on cancer-specific genomic or epigenetic alterations. Surgical techniques have also evolved towards less invasive approaches associated with less morbidity, without compromising oncological outcomes. With improvements in multidisciplinary care, advances in radiotherapy and new tools to detect minimal residual disease, certain patients may no longer even require surgical tumour resection. However, perhaps the most anticipated advance in the treatment of patients with oesophageal cancer is the advent of immune-checkpoint inhibitors, which harness and enhance the host immune response against cancer. In this Review, we discuss all these advances in the management of oesophageal cancer, representing only the beginning of a transformation in our quest to improve patient outcomes.

Brain-Mimicking Phantom for Photoablation and Visualization.

While the use of tissue-mimicking (TM) phantoms has been ubiquitous in surgical robotics, the translation of technology from laboratory experiments to equivalent intraoperative tissue conditions has been a challenge. The increasing use of lasers for surgical tumor resection has introduced the need to develop a modular, low-cost, functionally relevant TM phantom to model the complex laser-tissue interaction. In this paper, a TM phantom with mechanically and thermally similar properties as human brain tissue suited for photoablation studies and subsequent visualization is developed. The proposed study demonstrates the tuned phantom response to laser ablation for fixed laser power, time, and angle. Additionally, the ablated crater profile is visualized using optical coherence tomography (OCT), enabling high-resolution surface profile generation.

Renal Tumours Of Non-Clear Cell Histology; 10 Years' Experience In A Specialized Centre.

Non-clear cell renal cell carcinomas are uncommon renal tumours with diverse histologically and genetically defined entities. Due to limited clinical outcomes data, no standardized management approach can be offered to these patients. This study aimed to analyse outcomes of non clear cell renal cell carcinoma after surgical resection of localized renal tumours in our population. Patients with renal tumours who underwent partial or radical nephrectomy at the Department of Urology, from January 2010 to December 2019 were identified and evaluated, in terms of prevalence, presentation, recurrence, and survival outcome. Non-clear cell tumours were found in one-fourth of the total number of nephrectomies performed during this period for renal cell carcinoma (RCC). The mean age was 50.48±14.76 years (range 18-89 years) with 57% being of the male gender. The predominant types were chromophobe RCC, papillary RCC, and sarcomatoid RCC, in all non-clear cell renal tumours. Mean Recurrence Free Survival (RFS) for all tumours was 75.26±2.7 months. The projected 5 years RFS of papillary RCC, chromophobe RCC and sarcomatoid RCC were 94.2%, 84.3% and 62.5% respectively. RCC of non-clear-cell histology depicts excellent survival in patients with localized renal tumours. Furthermore, sarcomatoid RCC has worse recurrence free survival followed by chromophobe RCC and papillary RCC, in our population subset.

Machine learning prediction of venous thromboembolism after surgeries of major sellar region tumors

PurposeTo describe and predict the risk of venous thromboembolism (VTE) after surgical resection of major sellar region tumors. MethodPatients with sellar region tumors were identified from a database. The outcome was VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) within 60 days after surgery. We trained regression and machine learning models to predict the outcome using baseline characteristics, surgical findings and postoperative laboratory tests. ResultsAmong 3818 patients included, 124 patients developed VTE after surgery. The total 60-day VTE incidence was 3.2 %, with incidence peak within ten days after the surgery. The risk increased in patients >65 years old (OR 2.96, p < 0.001), in patients with chordoma (OR 3.40, p = 0.006) or craniopharyngioma (OR 1.86, p = 0.036), in patients underwent craniotomy approach (OR 2.78, p = 0.017), in patients with high volume CSF leakage (OR 4.24, p < 0.001), and in patients with longer surgical duration (OR 1.78, p = 0.029). The linear discriminant analysis algorithm had the highest AUC (0.869, 95%CI, 0.840–0.898) in predicting the outcome. The specificity, accuracy, and sensitivity of the best model were 61.8 %, 93.6 %, and 92.8 %, respectively. Risk stratification using our best model suggested that 1.3 % and 24.5 % of the patient developed VTE in the low-risk group and in the high-risk group, respectively. We developed an online decision-support tool available on https://deepvep.shinyapps.io/VTEpred/. ConclusionThe overall incidence of VTE after surgical resection of major sellar region tumors was clinically significant, especially in older patients with chordoma or craniopharyngioma.

Human intravital microscopy in the study of sarcomas: an early trial of feasibility.

ClinicalTrials.gov, identifier NCT03517852; ClinicalTrials.gov, identifier NCT03823144.

A prediction model of nodal metastasis in cN0 oral squamous cell carcinoma using metabolic and pathological variables

BackgroundThe efficacy of 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography(PET/CT) in evaluating the neck status in clinically node-negative (cN0) oral squamous cell carcinoma(OSCC) patients was still unsatisfying. We tried to develop a prediction model for nodal metastasis in cN0 OSCC patients by using metabolic and pathological variables.MethodsConsecutive cN0 OSCC patients with preoperative 18F-FDG PET/CT, subsequent surgical resection of primary tumor and neck dissection were included. Ninety-five patients who underwent PET/CT scanning in Shanghai ninth people’s hospital were identified as training cohort, and another 46 patients who imaged in Shanghai Universal Medical Imaging Diagnostic Center were selected as validation cohort. Nodal-status-related variables in the training cohort were selected by multivariable regression after using the least absolute shrinkage and selection operator (LASSO). A nomogram was constructed with significant variables for the risk prediction of nodal metastasis. Finally, nomogram performance was determined by its discrimination, calibration, and clinical usefulness.ResultsNodal maximum standardized uptake value(nodal SUVmax) and pathological T stage were selected as significant variables. A prediction model incorporating the two variables was used to plot a nomogram. The area under the curve was 0.871(Standard Error [SE], 0.035; 95% Confidence Interval [CI], 0.787–0.931) in the training cohort, and 0.809(SE, 0.069; 95% CI, 0.666–0.910) in the validation cohort, with good calibration demonstrated.ConclusionsA prediction model incorporates metabolic and pathological variables has good performance for predicting nodal metastasis in cN0 OSCC patients. However, further studies with large populations are needed to verify our findings.

Abstract 3963: Mass spectrometry reveals a downregulation of calreticulin after neoadjuvant chemotherapy in pancreatic cancer

Abstract Introduction: Pancreatic ductal adenocarcinomas are one of the deadliest cancer types with limited response to current therapies. Thus, this study examined changes in the proteome of epithelial cells in pancreatic cancer after neoadjuvant chemotherapy with gemcitabine, to identify new therapeutic targets. Methods: Upon receiving patient consent, fresh pancreatic cancer tissue was received from surgical tumor resections at the University Hospital of Bonn. We mechanically and enzymatically digested and purified the tissue to create single-cell suspensions. After staining the cells against CD45 und CD326, we purified epithelial cells, blood cells, and stroma through FACS. To analyze their proteome, the sorted cells were lysed in TEAB buffer and the protein lysates were measured by the mass spectrometry core facility at the University of Bonn. We then analyzed the data using DAVID and Shiny GO. Results: Gene enrichment analyses showed a significantly reduced expression of calreticulin after neoadjuvant chemotherapy in epithelial cells. A direct comparison between untreated and treated epithelium cancer cells using a heat map showed a decreased expression of actin and enzymes of glycolysis in treated cancer cells. Moreover, untreated epithelial cells showed an increase of proteins related to MHC class Ib protein complex assembly and antigen processing and presentation of endogenous peptide antigen via MHC class. In contrast, treated cells showed a higher presence of proteins for nutrient supply from the blood. Furthermore, untreated stroma cells exhibited an increased number of proteins responsible for mesenchymal migration and for actin filament fragmentation. Conclusion: This study shows that neoadjuvant chemotherapy with gemcitabine leads to distinct changes in the proteome of tumor cells in pancreatic cancers. In particular, a decreased expression of the “eat-me-signal” calreticulin impairs macrophage-mediated cancer cell phagocytosis, thereby indicating a mechanism by which cancer cells protect themselves after chemotherapy. Citation Format: Michael C. Stoffel, Elisabeth BH Dingendorf, Dahlia L. Kittel, Glen Kristiansen, Tristan Lerbs. Mass spectrometry reveals a downregulation of calreticulin after neoadjuvant chemotherapy in pancreatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3963.

Abstract 1349: Exploring CD63 as a targetable mediator of the pro-tumorigenic tissue microenvironment in HNSCC

Abstract Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancer types worldwide - ranked on the sixth position with 560,000 new diagnoses and 270,000 deaths in 2020. The survival could be increased only slightly over the past decades and in addition the incidence of HNSCC continues to rise. In this study, we investigated the role of the tetraspanin CD63 during cancer progression. Methods: First, we performed survival analyses with available statistics from data bases to correlate CD63 and survival. Then, we established a 20-marker spectral FACS panel to identify different fibroblast subpopulations in patient tissue. Upon receiving patient consent, fresh HNSCC tissue was received from surgical tumor resections at the University Hospital of Bonn. We mechanically and enzymatically digested and purified the tissue of ten patients to create single-cell suspensions. After staining, the cells were measured on a Sony ID7000 Spectral Analyzer and interpreted with FlowJo. To identify whether CD63 on fibroblasts affects the differentiation of macrophages in vitro, we isolated primary fibroblasts and monocytes from HNSCC patients and deleted CD63 in fibroblasts by CRISPR-Cas9. Thereafter, we co-incubated fibroblasts (without and with the CD63-Knockout) and macrophages over ten days in M-CSF containing medium, and measured the expression of M1 and M2 markers through flow cytometry. Results: First, correlating CD63 gene expression with the patient outcome showed that CD63 correlated with a decreased survival. Then, analyzing fresh tumor specimens with the multicolor panel showed an increase of CD63 expression in different fibroblast subpopulations in the tumor specimens, e. g. CD9+ CD34+ CD63+ CD90+ fibroblasts increased more than eightfold. Investigating potential mechanisms, by which CD63 expression on fibroblasts affects tumor progression, deleting CD63 steered macrophages towards the pro-inflammatory M1 phenotype. Conclusion: This study demonstrates that HNSCC increases CD63 expression in different fibroblast populations and that deleting CD63 on fibroblasts can steer macrophages towards the pro-inflammatory phenotype, thereby suggesting a rationale for testing CD63 as a therapeutic target. Citation Format: Elisabeth B. Dingendorf, Michael C. Stoffel, Dahlia L. Kittel, Glen Kristiansen, Tristan Lerbs. Exploring CD63 as a targetable mediator of the pro-tumorigenic tissue microenvironment in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1349.