Microscopic Tumor Growth Research Articles

Prediction of tumor growth at the microscopic level through mathematical modeling

All articles must contain an abstract. The abstract text should be formatted using 10 point Times or Times New Roman and indented 25 mm from the left margin. Set the pre-paragraph to 0 pounds and the post-break to 22.7 pounds. Starting on the same page as the abstract. The abstract should give readers concise information about the content of the article and indicate the main results obtained and conclusions drawn. The abstract is not part of the text and should be complete in itself; no table numbers, figure numbers, references or displayed mathematical expressions should be included. It should be suitable for direct inclusion in abstracting services and should not normally exceed 200 words in a single paragraph. Since contemporary information-retrieval systems rely heavily on the content of titles and abstracts to identify relevant articles in literature searches, great care should be taken in constructing both. To gain valuable insights into the growth of microscopic tumors, which is crucial for advancing cancer research, scientists employ mathematical modeling techniques. These models help researchers to comprehend how cells interact, proliferate, and organize spatially within tumors, ultimately aiding in developing better treatment strategies, including personalized medicine. A recent study introduced a novel approach using the Occam Plausibility Algorithm (OPAL) for modeling tumor growth. OPAL is a probabilistic framework adept at generating and refining hypotheses based on complex datasets. In this study, researchers integrated two existing models, the Proliferation Invasion Model (PIM) and the Mathematical Phase Field Model (MPFM), to create a comprehensive understanding of microscopic tumor growth dynamics. In this research, we have employed a literature review methodology to explore how researchers utilize three various mathematical modeling techniques, including the Occam Plausibility Algorithm (OPAL), to delve deeply into the growth dynamics of microscopic tumors. The conclusions drawn emphasize the significant potential of mathematical modeling in advancing scientists understanding of microscopic tumor growth.

Treatment of advanced squamous cell carcinoma of the external auditory canal: Critical analysis of persistent failures in diagnosis and surgery with a competing-risk model.

BackgroundA series of temporal bone squamous cell carcinomas (TBSCCs) was analyzed with the aim of (i) better understanding the causes for the persistent high failure rate in advanced SCCs and (ii) discussing a possible way out from this stalemate in treatment.MethodsForty‐five TBSCCs consecutively treated surgically were reviewed.ResultsThe 5‐year cumulative incidence for postoperative local recurrence was 41.8%. At multivariable analysis, pT3‐4 stages were associated with eightfold relative incidence of developing local recurrence during follow‐up (sHR = 9.06, 95% confidence interval [CI] = 1.18–69.46, p = 0.034) and cause‐specific death (sHR = 7.95, 95%CI = 1.01–62.27, p = 0.048).ConclusionsThe poor outcome in advanced TBSCC occurred because of local recurrence due to defective resection. The fundamental pitfall of surgery on advanced TBSCC appeared to be the insufficient knowledge of microscopic tumor growth in the different sites and subsites of the temporal bone. The serial histopathological study of the en bloc surgical specimen and autopsy temporal bones seems to represent a way to enhance our understanding of these tumors.

Do morphologic characteristics play a role in nodal metastatic progression of well-differentiated pancreatic neuroendocrine tumors?

Pancreatic neuroendocrine neoplasms (NENs) are tumors with histopathologic and prognostic heterogeneity that pose difficulties in establishing standards for diagnosis, classification, and treatment. Among NENs, well-differentiated neuroendocrine tumors (NETs) have been classified as grade 1, 2, and 3 in the most recently released World Health Organization classification. Although well-differentiated NETs are associated with relatively better prognosis, they have a potential for malignant behavior such as extrapancreatic spread, metastasis, or recurrence. The present study aimed to evaluate clinical and histomorphologic findings of patients with well-differentiated pancreatic NETs and to identify histopathologic findings effective in predicting nodal metastatic progression. The study group consisted of 54 patients diagnosed with well-differentiated NET. All preparations and blocks of the patients were examined for the following histopathologic parameters: tumor diameter, microscopic tumor growth pattern (solid, trabecular, acinar, and mixed), cellular features (clear, eosinophilic, oncocytic, peliotic, and pseudopapillary), stromal changes (calcification, lymphocytic infiltration, and stromal hyalinization), presence of necrosis, perineural invasion, lymphovascular invasion, mitotic activity, and Ki67 proliferative index. Lymph node metastasis was present in 7 patients. Lymph node metastasis was significantly associated with tumor diameter of >2 cm (p = 0.012), Ki67 proliferative index of >20% (p = 0.022), grade 3 tumors (p = 0.002), presence of dense stromal hyalinization (p = 0.034), and mild lymphocytic infiltration (p = 0.041). The present study revealed that the new findings such as presence of dense stromal hyalinization and absence of remarkable lymphocytic infiltration could be predictive morphologic findings for the development of lymph node metastasis.

Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression.

BackgroundHyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study’s objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management.MethodsWe assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts.ResultsWe showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier.ConclusionsFor the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks.

Spatially quantifying microscopic tumor invasion and proliferation using a voxel‐wise solution to a glioma growth model and serial diffusion MRI

The purpose of this study was to develop a voxel-wise analytical solution to a glioma growth model using serial diffusion MRI. These cell invasion, motility, and proliferation level estimates (CIMPLE maps) provide quantitative estimates of microscopic tumor growth dynamics. After an analytical solution was found, noise simulations were performed to predict the effects that perturbations in apparent diffusion coefficient values and the time between apparent diffusion coefficient map acquisitions would have on the accuracy of CIMPLE maps. CIMPLE maps were then created for 53 patients with gliomas with WHO grades of II-IV. MR spectroscopy estimates of the choline-to-N-acetylaspartate ratio were compared to cell proliferation estimates in CIMPLE maps using Pearson's correlation analysis. Median differences in cell proliferation and diffusion rates between WHO grades were compared. A strong correlation (R(2) = 0.9714) and good spatial correspondence were observed between MR spectroscopy measurements of the choline-to-N-acetylaspartate ratio and CIMPLE map cell proliferation rate estimates. Estimates of cell proliferation and diffusion rates appear to be significantly different between low- (WHO II) and high-grade (WHO III-IV) gliomas. Cell diffusion rate (motility) estimates are highly dependent on the time interval between apparent diffusion coefficient map acquisitions, whereas cell proliferation rate estimates are additionally influenced by the level of noise present in apparent diffusion coefficient maps.

Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab′)2

To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.

Real-time whole-body imaging of an orthotopic metastatic prostate cancer model expressing red fluorescent protein.

We describe here, a whole-body imageable spontaneous metastatic model of human prostate cancer developed by surgical orthotopic implantation (SOI) and visualized by red fluorescent protein (RFP) expression. Human prostate cancer PC-3 cells were transduced with the pLNCX2-DsRed-2-RFP retroviral vector containing the RFP and neomycin-resistance genes. A stable RFP-expressing PC-3 clone was selected in 800 microg/ml G418 in vitro and injected subcutaneously in nude mice. Stable high-level expression of RFP was maintained in the subcutaneously-growing tumors. To utilize RFP expression for metastasis studies, fragments of the subcutaneously-growing tumor, which were comprised of RFP-expressing cells, were implanted by SOI in the prostate of nude mice. Primary tumor growth, progression, and subsequent lymphatic metastases were visualized in live, intact animals in real time by whole-body RFP fluorescence imaging. In total, 100% of the experimental animals developed lymphatic metastasis, the growth of which was monitored in real time by whole-body imaging. The aggressive lymphatic metastasis in this model reflects one of the major metastatic routes of prostate cancer in human patients. Intravital RFP imaging visualized single cancer cells in the lung and bladder. Open RFP imaging at autopsy visualized extensive primary growth and highly disseminated lymph-node metastases. The long-wavelength emission of RFP enabled high sensitivity and resolution of microscopic tumor growth using appropriate imaging techniques. The model should be useful for the real-time evaluation of novel therapeutics for metastatic prostate cancer.

Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation.

Ionizing radiation (IR) is frequently unsuccessful in the treatment of cancer because of local failure or distant metastases. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. We report that intratumoral injection of an adenoviral vector with interleukin-12 (IL-12) enhances local anti-tumor effects of irradiation (IR). We demonstrate that microscopic tumor growth at a distant site is suppressed following treatment of the primary tumor with adeno-murine IL-12 (Adm.IL-12). The results support a model in which the anti-angiogenic effects of IL-12 contribute to the local anti-tumor effects of radiation, while IL-12 induced immunity suppresses growth of microscopic tumors distant from the primary irradiated site. These data suggest that combining radiotherapy with IL-12 improves both local and distant tumor control compared to either treatment alone. Immunoradiotherapy may be employed in addition to or in place of current conventional therapies to increase local control and decrease distant tumor growth.

An immunohistochemical study of the expression of p53 protein in colon cancer.

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.

R�ntgenbefunde und mikroskopisches Wachstum von malignen Larynxtumoren

In a serie of laryngices with malignant tumors, which have been achieved by laryngectomie, the microscopic tumor growth in its total has been recognised in histological sections and has been compaired with the result of the pre-operative radiological examination (tomographie, laryngographie) of the larynx.