CD10 Expression Correlates with Earlier Tumour Stages and Left-Sided Tumour Location in Colorectal Cancer but Has No Prognostic Impact in a European Cohort.

The role of CD10 expression in colorectal cancer has been controversially discussed in the literature. Some data suggest a predictive capacity for lymph node and liver metastases, thus influencing overall survival (OS) and disease-free survival (DFS). This study aims to analyse the relationship between CD10 expression and overall survival (OS) in a European cohort. To determine the association of CD10 expression with tumour phenotype, molecular features, and prognosis, a tissue microarray of 1469 colorectal carcinomas was analysed using immunohistochemistry and was compared with matched clinicopathologic data. CD10 expression correlated with earlier tumour stages (p = 0.017) and left-sided colon cancer (p < 0.001). However, no correlation was found between CD10 expression and lymph node involvement (p = 0.711), tumour grading (p = 0.397), or overall survival (p = 0.562). Even in the subgroup analysis of tumour or nodal stage, CD10 did not affect overall survival, although it was significantly associated with p53 and nuclear ß-catenin expression (p = 0.013 and p < 0.001, respectively). CD10 expression correlates with earlier tumour stages, colon cancer location, and indicators of aggressive CRC subtypes. However, we can exclude CD10 as a relevant independent prognosticator for CRC.

Parkinson's Disease and Subjective Prospects for the Future in Different Life Domains. Findings of a Nationally Representative Sample.

Purpose: To analyze the link between Parkinson's disease and perceived prospects for the future. Patients and Methods: Data were taken from the German Ageing Survey (year 2021; n=4296 individuals, thereof 33 individuals with Parkinson's disease) were used. This is a nationally representative sample of community-dwelling individuals ≥ 40 years in Germany. Perceived prospects for the future in different life domains (ie, living standard, health and general optimism) were used as outcomes. Physician-diagnosed Parkinson's disease served as key independent variable . It was adjusted for several covariates. Results: Individuals with Parkinson's disease had a markedly worse (Cohen's d=0.65) general optimism compared to individuals without Parkinson's disease. After adjusting for various factors, these differences disappeared in multiple linear regressions (ß=-0.04, p=0.72). Moreover, multiple ordered logistic regressions showed that individuals with Parkinson's disease had a worse future self-rated health (OR: 4.10, 95% CI: 1.99-8.47, p<0.001) compared to individuals without Parkinson's disease. Conclusion: Our study first showed that general optimism may be lower among individuals with Parkinson's disease (bivariate analysis). However, this association disappeared when it was adjusted for health-related factors in regression analysis. In sum, our findings indicate that more general future-related factors did not significantly differ between individuals with and without Parkinson's disease. However, there were significant differences in future self-rated health.

Loneliness and Social Isolation among Transgender and Gender Diverse People.

Here, we report the prevalence of loneliness and social isolation and investigate the levels of loneliness and social isolation among transgender and gender diverse people using cross-sectional data from the HH-TPCHIGV study. Using the De Jong Gierveld tool, we assess loneliness, using the Bude and Lantermann tool, we assess perceived social isolation and using the Lubben Social Network Scale, we assess objective social isolation. The prevalence rate of loneliness was 83.3% (perceived social isolation: 77.7%; objective social isolation: 34.4%). Regressions revealed that favorable outcomes (i.e., lower loneliness levels, lower perceived social isolation, and lower objective social isolation) were consistently associated with higher school education. Beyond that, we identify an association between particularly poor health-related factors and higher loneliness and objective social isolation levels. We also report that unemployment was significantly associated with higher levels of perceived social isolation. In conclusion, we show high prevalence rates of loneliness and social isolation among transgender and gender diverse people. Additionally, important correlates (e.g., education, health-related factors, or unemployment) were identified. Such knowledge may provide help to address transgender and gender diverse people at risk for loneliness and social isolation.

Are transgender people satisfied with their lives?

BACKGROUND: Our goal was to examine the proportion of transgender people satisfied with their lives (i.e., cognitive evaluation of life as a whole) and the determinants of life satisfaction level among transgender individuals. METHODS: Data were taken from the HH-TPCHIGV study. Included were 104 transgender people who had joined self-help groups to get and share information about the gender-affirming surgeries performed at the Division of Plastic, Reconstructive and Aesthetic Surgery at the University Medical Center Hamburg-Eppendorf. The established Satisfaction with Life Scale was used to quantify life satisfaction. Sociodemographic-, lifestyle-related and health-related determinants were included in multiple linear regressions. In regression analysis, life satisfaction served as outcome measure and in a robustness check ordered probit regressions were used. RESULTS: Among transgender people, 12.9% can be classified as "extremely dissatisfied", 18.3% can be classified as "dissatisfied", 12.9% can be classified as "slightly dissatisfied", 7.5% as "neutral", 30.1% as "slightly satisfied", 17.2% as "satisfied" and 1.1% as "extremely satisfied". Higher levels of life satisfaction were associated with higher age (ß = .15, p < .05), higher school education (ß = 5.54, p < .001), and favorable self-rated health (ß = 2.20, p < .001). CONCLUSIONS: Nearly half of the transgender people were at least "satisfied" with their lives. Knowledge about the correlates of life satisfaction may assist in addressing unsatisfied individuals.

Long-term care need, loneliness, and perceived social isolation during the COVID-19 pandemic: evidence from the German Ageing Survey.

BACKGROUND: There is a complete lack of studies focusing on the association between care degree (reflecting the long-term care need) and loneliness or social isolation in Germany. AIMS: To investigate the association between care degree and loneliness as well as perceived social isolation during the COVID-19 pandemic. METHODS: We used data from the nationally representative German Ageing Survey, which covers community-dwelling middle-aged and older individuals aged 40 years or over. We used wave 8 of the German Ageing Survey (analytical sample: n = 4334 individuals, mean age was 68.9 years, SD: 10.2 years; range 46-100 years). To assess loneliness, the De Jong Gierveld instrument was used. To assess perceived social isolation, the Bude and Lantermann instrument was used. Moreover, the level of care was used as a key independent variable (absence of care degree (0); care degree 1-5). RESULTS: After adjusting for various covariates, regressions showed that there were no significant differences between individuals without a care degree and individuals with a care degree of 1 or 2 in terms of loneliness and perceived social isolation. In contrast, individuals with a care degree of 3 or 4 had higher loneliness (ß = 0.23, p = 0.034) and higher perceived social isolation scores (ß = 0.38, p < 0.01) compared to individuals without a care degree. DISCUSSION/CONCLUSIONS: Care degrees of 3 or 4 are associated with higher levels of both loneliness and perceived social isolation. Longitudinal studies are required to confirm this association.

Decreased expression of prolyl hydroxylase 1 is associated with poor prognosis in colorectal cancers.

BACKGROUND: Prolyl hydroxylase 1 (PHD1) is a prognostic marker in several cancers. AIMS AND SCOPES: This study was undertaken to elucidate the clinical relevance of PHD1 in colorectal cancer (CRC) prognosis. MATERIALS AND METHODS: We compared PHD1 expression on a tissue microarray (TMA) containing samples from 1800 CRCs with corresponding clinicopathological tumor variables and patient survival. RESULTS: While PHD1 staining was always high in benign colorectal epithelium, high PHD1 staining was detectable in only 71.8% of CRCs. Low PHD1 staining was associated with advanced tumor stage (p = 0.0101) and shortened overall survival in CRC patients (p = 0.0011). In a multivariable analysis including tumor stage, histological type and PHD1 staining revealed tumor stage and histological type (p < 0.0001 each), but also PHD1 staining (p = 0.0202) to be independent prognostic markers for CRC. CONCLUSIONS: In our cohort, loss of PHD1 expression independently identified a subset of CRC patients with poor overall survival and might, thus, be a promising prognostic marker. PHD1 targeting may even allow for specific therapeutic approaches for these patients.

Prevalence and Determinants of Depressive and Anxiety Symptoms among Transgender People: Results of a Survey.

OBJECTIVES: The aim was to investigate the prevalence of probable depression and probable anxiety and to investigate the determinants of depressive symptoms and anxiety symptoms among transgender people. METHODS: In this "Transgender Survey" (n = 104) we included transgender people who had joined self-help groups to obtain and share information about the gender-affirming surgeries performed at the Division of Plastic, Reconstructive and Aesthetic Surgery at the University Medical Center Hamburg-Eppendorf. Data collection took place between April and October 2022. To measure probable depression, the patient health questionnaire-9 was used. The generalized anxiety disorder-7 was used to quantify probable anxiety. RESULTS: The prevalence of probable depression was 33.3% and it was 29.6% for probable anxiety. Multiple linear regressions showed that both more depressive symptoms and anxiety symptoms were significantly associated with younger age (ß = -0.16, p < 0.01; ß = -0.14, p < 0.01), being unemployed (e.g., full-time employed compared to unemployment: ß = -3.05, p < 0.05; ß = -2.69, p < 0.05), worse self-rated health (ß = -3.31, p < 0.001; ß = -1.88, p < 0.05), and having at least one chronic disease (ß = 3.71, p < 0.01; ß = 2.61, p < 0.05). CONCLUSIONS: Remarkably high prevalence rates were identified among transgender people. Furthermore, risk factors of poor mental health (e.g., unemployment or younger age) were identified-which can help to address transgender people at risk for poor mental health.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.

PURPOSE: Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). METHODS: RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. RESULTS: While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915). CONCLUSION: Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

CD147 expression lacks prognostic relevance in esophageal cancer.

INTRODUCTION: The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world. METHODS: To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data. RESULTS: CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer. CONCLUSION: Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.

Truncated O-GalNAc glycans impact on fundamental signaling pathways in pancreatic cancer.

Truncated O-GalNAc glycosylation is an important feature of pancreatic ductal adenocarcinomas (PDAC) and expression of truncated O-GalNAc glycans is strongly associated with decreased survival and poor prognosis. It has been proven, that aberrant O-GalNAc glycosylation influence PDAC signaling to promote oncogenic properties, but elucidation of the influence of truncated O-GalNAc glycosylation on different signaling molecules has just been started. We herein elucidated the impact of aberrant O-GalNAc glycosylation on two important PDAC signaling pathways, namely AKT/mTOR and RAS/MAPK. In PDAC cells expressing truncated O-GalNAc glycans, we identified differentially expressed proteins associated with AKT/mTOR and RAS/MAPK pathways using quantitative proteomics. Since AKT, a key-signaling molecule in PDAC, was among the identified proteins, we analyzed AKT and found a strikingly enhanced S473 phosphorylation and identified a previously unknown O-GalNAc-modification. Consecutive analysis of COSMC knockdowns in PDAC revealed strong effects on AKT upstream and downstream effector molecules. Interestingly, truncated O-GalNAc glycans could facilitate an mTORC1 inhibitor resistance using AZD8055. In addition, as AKT/mTOR pathway has extensive cross talks with RAS/MAPK pathway we analyzed the pathways and found it negatively regulated. Finally, we found that the expression of epithelial-mesenchymal-transition markers, key features of aggressive PDACs cells, are enhanced and truncated O-GalNAc glycans enhance pancreatic cancer cell growth in a xenograft mouse model. Our study demonstrates that truncated O-GalNAc glycans have a strong impact on AKT/mTOR and RAS/MAPK signaling pathways, are modulated by EGF or IGF-1 signaling and should be considered for targeted therapy of these pathways in PDAC.

Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients.

INTRODUCTION: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients. RESULTS: In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085). CONCLUSION: However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers.

Acute Mesenteric Infarction: The Chameleon of Acute Abdomen Evaluating the Quality of the Diagnostic Parameters in Acute Mesenteric Ischemia.

INTRODUCTION/OBJECTIVE: Acute mesenteric ischemia (AMI) is difficult to diagnose. Since the established parameters have low sensitivity and specificity, the aim of this study is to analyze the diagnostic quality of the established parameters of AMI. METHODS: All patients that underwent emergency surgery due to suspected diagnosis of mesenteric ischemia at the University Medical Center Hamburg-Eppendorf between 2008 and 2014 were evaluated. Overall, 275 patients were enrolled and pre-, intra- and postoperative data were evaluated. RESULTS: In 200 patients, a mesenteric ischemia was confirmed intraoperatively, and 75 patients had no ischemia. Comparing these groups, the rate of patients with pH < 7.2 (25 vs. 12%; p = 0.021) and elevated mean CRP level (175 ± 117 mg/L vs. 139 ± 104 mg/L; p = 0.019) was significantly higher in ischemic patients. There was no significant difference in the level of preoperative lactate. Concerning abdominal CT scan, a sensitivity and specificity of 61 and 68%, respectively, was found. CONCLUSION: New diagnostic parameters are needed. So far, explorative laparotomy is the only reliable diagnostic method to detect mesenteric infarction.

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer.

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.

Cholecystokinin-8 treatment reduces acinar necrosis and edema of pigs with induced pancreatitis.

BACKGROUND: Acute pancreatitis is an inflammatory process of the pancreas and a leading cause of hospitalization amongst gastrointestinal disorders. Previously, cholecystokinin (CCK) has been described to play a role in regeneration of pancreas. The aim of this study was to analyse the function of cholecystokinin octapeptide (CCK-8) during induced pancreatitis in an animal model. METHODS: Overall acute pancreatitis was induced in 38 pigs. After the induction of acute pancreatitis, half of the animals were treated with CCK-8. Intraoperative clinical data, postoperative blood parameters, 'Porcine Well-being' (PWB) and fitness score and post-mortal histopathological data were analysed. RESULTS: At baseline, physiologically parameters of the pigs of both groups were comparable. No differences were observed regarding the overall survival of animals (p = 0.97). Postoperative PWB score were significantly enhanced in animals treated with CCK-8 as compared to the control group (p = 0.029). Moreover, histopathological analysis of the pancreatic tissue revealed that acinar necrosis and edema were significant reduced in the CCK-8 group in comparison to the control group (p = 0.016 and p = 0.019). CONCLUSIONS: In conclusion, we found that CCK-8 treatment reduces acinar necrosis and edema of pancreatic tissue after induction of an acute pancreatitis in pigs.

C-Reactive Protein in the Prediction of Localization of Gastrointestinal Perforation.

AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. METHODS: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. RESULTS: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). CONCLUSION: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.

Microbial findings, sensitivity and outcome in patients with postoperative peritonitis a retrospective cohort study.

BACKGROUND: Acute postoperative peritonitis resulting from previous abdominal surgery is still a severe and potentially fatal disease, which is associated with high morbidity and mortality. The aim of the present study was to evaluate patients' outcome after postoperative peritonitis and identify the most effective empiric antibiotic regimes. METHODS: 422 patients with acute postoperative peritonitis as a result to earlier abdominal operation (e.g. anastomotic leakage) were analyzed retrospectively focusing on the origin of the peritonitis, microbial flora and resistance patterns. Furthermore, mortality was estimated according to sensitivity results of the tested antibiotics. RESULTS: In 50% of the patients, anastomotic leakage was located in the colon. The predominantly cultured microorganisms were Escherichia coli and Enterobacteriaceae. The combination of meropenem and vancomycin was effective in 96% of these microbes. The frequently used combinations of piperacillin/sulbactam and cefotaxime/metronidazole were effective in only 67% and 43%, respectively. CONCLUSIONS: We were able to show that the currently used antibiotic regimes with piperacillin/sulbactam and cefotaxime/metronidazole are ineffective in a relevant number of patients with anastomotic leakage. Only meropenem or meropenem/vancomycin cover most of the microbes predominant in postoperative peritonitis.

Clinical outcome of patients undergoing abdominoplasty after massive weight loss.

BACKGROUND: Abdominoplasty is one of the most commonly performed surgical procedures to reshape the body contour in patients who have undergone massive weight loss. OBJECTIVES: This study was undertaken to assess the clinical outcome, complication rates, and risk factors for complications of patients undergoing abdominoplasty after massive weight loss. SETTING: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. METHOD: Clinical outcome was retrospectively analyzed in 121 patients, who underwent abdominoplasty. The retrospective analysis included demographic data of patients, such as sex, age, body mass index (BMI), and pre-existing illnesses. Moreover, postoperative complications including seroma, hematoma, wound infection, and tissue necrosis were analyzed. RESULTS: In our study cohort, the median age was 43.7 years, the median weight was 94.7 kg, and the median BMI was 32.3 kg/m2. The majority of included patients were women (70.3%). Death occurred in none of the patients. Among individuals, wound infection occurred in 3.3%, tissue necrosis in 1.7%, seroma in 7.4%, and hematoma in 3.3% of patients during the postoperative course. Reoperations were necessary in 2 patients (1.7%) due to postoperative bleeding and tissue necrosis of the navel. Tissue necrosis was significantly more often seen in a subset individual with type 2 diabetes (P = .006). Moreover, the rate of reoperations was significantly higher in patients with pre-existing cardiovascular illnesses compared with cardiovascular healthy patients (P = .036). Multivariate analysis analyzing risk factors for postoperative complications, including sex, age, BMI, diabetes, pulmonary disease, and cardiovascular disease, revealed strong independent relevance for type 2 diabetes (P = .024). CONCLUSIONS: We found that abdominoplasty is a safe operative procedure. In addition, the risk for complications is significantly increased in the subgroup of diabetic patients and patients with cardiovascular diseases.

Aberrant expression of Sec61α in esophageal cancers.

INTRODUCTION: The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients. MATERIALS AND METHODS: Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry. RESULTS: Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751). CONCLUSIONS: Thus, Sec61α measurement has not an additional prognostic benefit for the patients.

Separating Response of Tumor and non-Tumor Cells to Drug In Vitro by Quantifying a Mutation.

BACKGROUND/AIM: Conventional in vitro assays measure the effect of drugs on total cells, while separating the effect to those on tumor and non-tumor cells is important for assessing drug specificity. Our aim was to evaluate the feasibility of separating the efficacy of vemurafenib on tumor and non-tumor cells in a mixed culture. MATERIALS AND METHODS: Melanoma A2058 cells and CCD18Co non-tumor cells were mixed and treated with vemurafenib. DNA was subjected to digital PCR to determine the ratio of the mutant 1799A to the wild-type 1799T alleles and viabilities of total cells were subsequently calculated as percentages of tumor and non-tumor cells. RESULTS: The set-up proportion of tumor cells correlated well with the calculated one. The calculated viability of tumor cells decreased with increasing doses of vemurafenib while that of the non-tumor cells remained rather constant. Variability of digital PCR data was high. CONCLUSION: Using the BRAF mutation 1799T>A to separate the response of tumor and non-tumor cells to a drug, such as vemurafenib, is feasible, supporting a foundation for a genetic in vitro tool for testing drug efficacy and specificity.