Early Colon Carcinoma Research Articles

Changes of Kinesin Family Member 18 Pathway in Epithelial Mesenchymal Transformation and Effect of Butyrate on Migration and Invasion of Colon Cancer Cells

Colon cancer is a common digestive system disease with an increasing incidence. Severe migration and invasion aggravates the deterioration of colon cancer patients. Previous studies have found that epithelial mesenchymal transition (EMT) is closely associated with early transference of colon carcinoma and abnormal changes occur in KIF18 signaling pathway. Butyrate protects colonic mucosa with a considerable effect on the colon. This study predicts that butyrate may reverse EMT process of colon cancer cells through KIF18 signaling pathway, thereby inhibiting cell migration and invasion. In this experiment, EMT model of colon cancer was used to investigate migration and invasion. Human colon cancer cell line SW1116 was cultured and assigned into control group (0 mmol/L butyrate), low concentration group (2 mmol/L), medium concentration group (4 mmol/L), and high concentration group (10 mmol/L). After 72 hours, cell migration and invasion was analyzed by Transwell assays. E-cadherin, Vimentin, and KIF18 level was detected by Western blot and quantitative real-time PCR. After treatment, cell migration and invasion was significantly inhibited compared to control dose-dependently. In addition, Vimentin and KIF18 mRNA level was significantly lower and E-cadherin mRNA was higher in treatment groups than control group in a dose-dependent manner (P < 0.05). Consistently, the profile of protein level of these molecules was similar to mRNA expression profile. Electron microscope showed that after treatment with butyrate, the surface protuberances of colon cancer cells were abnormally increased, especially the vesicular protuberances, which were the microvilli of intestinal mucosal epithelium. In conclusion, KIF18 is crucial in EMT of colon cancer cells. Butyrate may elevate E-cadherin and suppress Vimentin and KIF18 by activating KIF18 signaling, thus inhibiting invasion and migration.

Novel Nomograms to Predict Lymph Node Metastasis and Liver Metastasis in Patients with Early Colon Carcinoma

Background: Lymph node status and liver metastasis (LIM) are important in determining the prognosis of early colon carcinoma. We attempted to develop and validate nomograms to predict lymph node metastasis (LNM) and LIM in patients with early colon carcinoma. Methods: A total of 32,819 patients who underwent surgery for pT1 or pT2 colon carcinoma were enrolled in the study based on their records in the SEER database. Risk factors for LNM and LIM were assessed based on univariate and multivariate binary logistic regression. The C-index and calibration plots were used to evaluate LNM and LIM model discrimination. The predictive accuracy and clinical values of the nomograms were measured by decision curve analysis. The predictive nomograms were further validated in the internal testing set. Results: The LNM nomogram, consisting of seven features, achieved the same favorable prediction efficacy as the five-feature LIM nomogram. The calibration curves showed perfect agreement between nomogram predictions and actual observations. The decision curves indicated the clinical usefulness of the prediction nomograms. Receiver operating characteristic curves indicated good discrimination in the training set (area under the curve [AUC] = 0.667, 95% CI=0.661-0.673) and the testing set (AUC=0.658, 95% CI=0.649-0.667) for the LNM nomogram and encouraging performance in the training set (AUC=0.766, 95% CI=0.760-0.771) and the testing set (AUC=0.825, 95% CI=0.818-0.832) for the LIM nomogram. Conclusion: Novel validated nomograms for patients with early colon carcinoma can effectively predict the individualized risk of LNM and LIM, and this predictive power may help doctors formulate suitable individual treatments.

Glandular orientation and shape determined by computational pathology could identify aggressive tumor for early colon carcinoma: a triple-center study

BackgroundIdentifying the early-stage colon adenocarcinoma (ECA) patients who have lower risk cancer vs. the higher risk cancer could improve disease prognosis. Our study aimed to explore whether the glandular morphological features determined by computational pathology could identify high risk cancer in ECA via H&E images digitally.Methods532 ECA patients retrospectively from 2 independent data centers, as well as 113 from The Cancer Genome Atlas (TCGA), were enrolled in this study. Four tissue microarrays (TMAs) were constructed across ECA hematoxylin and eosin (H&E) stained slides. 797 quantitative glandular morphometric features were extracted and 5 most prognostic features were identified using minimum redundancy maximum relevance to construct an image classifier. The image classifier was evaluated on D2/D3 = 223, D4 = 46, D5 = 113. The expression of Ki67 and serum CEA levels were scored on D3, aiming to explore the correlations between image classifier and immunohistochemistry data and serum CEA levels. The roles of clinicopathological data and ECAHBC were evaluated by univariate and multivariate analyses for prognostic value.ResultsThe image classifier could predict ECA recurrence (accuracy of 88.1%). ECA histomorphometric-based image classifier (ECAHBC) was an independent prognostic factor for poorer disease-specific survival [DSS, (HR = 9.65, 95% CI 2.15–43.12, P = 0.003)]. Significant correlations were observed between ECAHBC-positive patients and positivity of Ki67 labeling index (Ki67Li) and serum CEA.ConclusionGlandular orientation and shape could predict the high risk cancer in ECA and contribute to precision oncology. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.

Novel nomograms to predict lymph node metastasis and liver metastasis in patients with early colon carcinoma

BackgroundLymph node status and liver metastasis (LIM) are important in determining the prognosis of early colon carcinoma. We attempted to develop and validate nomograms to predict lymph node metastasis (LNM) and LIM in patients with early colon carcinoma.MethodsA total of 32,819 patients who underwent surgery for pT1 or pT2 colon carcinoma were enrolled in the study based on their records in the SEER database. Risk factors for LNM and LIM were assessed based on univariate and multivariate binary logistic regression. The C-index and calibration plots were used to evaluate LNM and LIM model discrimination. The predictive accuracy and clinical values of the nomograms were measured by decision curve analysis. The predictive nomograms were further validated in the internal testing set.ResultsThe LNM nomogram, consisting of seven features, achieved the same favorable prediction efficacy as the five-feature LIM nomogram. The calibration curves showed perfect agreement between nomogram predictions and actual observations. The decision curves indicated the clinical usefulness of the prediction nomograms. Receiver operating characteristic curves indicated good discrimination in the training set (area under the curve [AUC] = 0.667, 95% CI 0.661–0.673) and the testing set (AUC = 0.658, 95% CI 0.649–0.667) for the LNM nomogram and encouraging performance in the training set (AUC = 0.766, 95% CI 0.760–0.771) and the testing set (AUC = 0.825, 95% CI 0.818–0.832) for the LIM nomogram.ConclusionNovel validated nomograms for patients with early colon carcinoma can effectively predict the individualized risk of LNM and LIM, and this predictive power may help doctors formulate suitable individual treatments.

Novel Nomograms to Predict Lymph Node Metastasis and Liver Metastasis in Patients with Early Colon Carcinoma

Lymph node status and liver metastasis (LIM) are important in determining the prognosis of early colon carcinoma. We attempted to develop and validate nomograms to predict lymph node metastasis (LNM) and LIM in patients with early colon carcinoma. A total of 32,819 patients who underwent surgery for pT1 or pT2 colon carcinoma were enrolled in the study based on their records in the SEER database. Risk factors for LNM and LIM were assessed based on univariate and multivariate binary logistic regression. The C-index and calibration plots were used to evaluate LNM and LIM model discrimination. The predictive accuracy and clinical values of the nomograms were measured by decision curve analysis. The predictive nomograms were further validated in the internal testing set. The LNM nomogram, consisting of seven features, achieved the same favorable prediction efficacy as the five-feature LIM nomogram. The calibration curves showed perfect agreement between nomogram predictions and actual observations. The decision curves indicated the clinical usefulness of the prediction nomograms. Receiver operating characteristic curves indicated good discrimination in the training set (area under the curve [AUC] = 0.667, 95% CI=0.661-0.673) and the testing set (AUC=0.658, 95% CI=0.649-0.667) for the LNM nomogram and encouraging performance in the training set (AUC=0.766, 95% CI=0.760-0.771) and the testing set (AUC=0.825, 95% CI=0.818-0.832) for the LIM nomogram. Novel validated nomograms for patients with early colon carcinoma can effectively predict the individualized risk of LNM and LIM, and this predictive power may help doctors formulate suitable individual treatments. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81572407, 81602112, 81672405, 81702404 ); Key project of Natural Science Foundation of Guangdong Province, China (No. 4210016041); Science and Technology Program of Guangdong Province, China (No.2015A030313096, 2016A030313184, 2017A030313536); Natural Science Foundation of Guangzhou, China (No. 4250016043). Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The ethics committee board of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, approved the use of patients with early colon carcinoma for this study.

MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma.

Worldwide, colon cancer is among the most common cancer entities. Understanding the molecular background is the key to enable accurate stage determination, which is crucial to assess optimal therapy options. The search for preoperative biomarkers is ongoing. In recent years, several studies have proposed a diagnostic and prognostic role for miRNAs in cancer. Aim of this study was to evaluate miRNA expression patterns correlating with tumor stage, especially lymph node metastasis, in primary colon carcinoma tissue. Screening was accomplished using GeneChip® miRNA v3.0 arrays (Thermo Fisher Scientific, Waltham, MA, USA) and validated via TaqMan® qPCR assays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate miRNA expressions in 168 FFPE and 83 fresh frozen colon carcinoma samples. Regarding lymph node status, analyses displayed no significantly differential miRNA expression. Interestingly, divergent expression of miR-18a-5p, miR-20a-5p, miR-21-5p, miR-152-3p and miR-1973 was detected in stage pT1. Although miRNAs might not represent reliable biomarkers regarding lymph node metastasis status, they could support risk assessment in stage T1 tumors.

Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden

BackgroundColorectal cancer (CRC) screening programs result in the detection of early-stage asymptomatic carcinomas suitable to be surgically cured. Lymph nodes (LN) from early CRC are usually small and may be difficult to collect. Still, at least 12 LNs should be analyzed from colectomies, to ensure a reliable pN0 stage. Presurgical endoscopic tattooing improves LN procurement. In addition, molecular detection of occult LN tumor burden in histologically pN0 CRC patients is associated with a decreased survival rate. We aimed to study the impact of presurgical endoscopic tattooing on the molecular detection of LN tumor burden in early colon neoplasms.MethodsA prospective cohort study from a CRC screening-based population was performed at a tertiary academic hospital. LNs from colectomies with and without preoperative endoscopic tattooing were assessed by two methods, hematoxylin and eosin (HE), and RT-LAMP, to detect tumor cytokeratin 19 (CK19) mRNA. We compared the amount of tumor burden and LN yields from tattooed and non-tattooed specimens.ResultsHE and RT-LAMP analyses of 936 LNs were performed from 71 colectomies containing early carcinomas and endoscopically unresectable adenomas (8 pT0, 17 pTis, 27 pT1, 19 pT2); 47 out of 71 (66.2 %) were tattooed. Molecular positivity correlated with the presence of tattoo in LN [p < 0.001; OR 3.1 (95 % CI 1.7–5.5)]. A significantly higher number of LNs were obtained in tattooed specimens (median 17 LN vs. 14.5 LN; p = 0.019).ConclusionsEndoscopic tattooing enables the analysis of those LNs most prone to harbor tumor cells and improves the number of LN harvested.

Early diagnosis of the colon carcinoma during the treatment with acitretin

Sir, Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis and various other skin disorders, such as lichen planus, ichthyosis, lupus erythematosus. The mechanism of action of acitretin is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. The most frequent adverse reactions associated with this drug are the mucocutaneous effects on the lips, eyes, mouth, and other epidermal surfaces [1]. Herein, we present a case of a 54-year old man who developed rectal bleeding and detection of early stage colon carcinoma during the treatment with systemic acitretin for psoriasis vulgaris. A 54-year old man with 15-year history of psoriasis vulgaris, resistant to several topical agents, was presented to our out-patient clinic. He had generalised erythematous plaques. His only other medical problem was diabetes mellitus. Routine laboratory tests were normal. Therapy with oral acitretin (25 mg/day) was initiated. A month after starting the acitretin treatment, he developed symptoms of rectal bleeding which was intensified by defecation. He also complained of cheilitis, xerosis, and eye dryness. The patient was referred to department of general surgery. Abdominal examination was unremarkable. Pelvic ultrasonography did not revealed any abnormalities. Stool examination for occult blood was negative, and tumor markers (CEA, CA19.9) were normal. The colonoscopy was performed and this revealed a flat polyp measuring 2,5×1,7x1,5 cm located in the sigmoid colon. Snear polypectomy was performed. A histological evaluation revealed a well differentiated adenocarcinoma penetrating the submucosa. Histologically, the tumor was composed of neoplastic cells that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and CT scanning with positron-emission tomography (PET-CT) showed no evidence of primary lesions or distant metastasis. Based on clinical and histopathological features, a diagnosis of early stage colon carcinoma was made. We suspected that the acitretin was causing the complaints and recommended discontinuation of the drug. Once this occurred, the problems subsided gradually over the next two weeks. Acitretin is a retinoid drug used for systemic treatment of severe cases of psoriasis and keratinization disorders. The most common side-effects of acitretin are dry lips and cheilitis, occuring in up to 75-100 % of patients. Other mucocutaneous effects include conjunctivitis, dry nose, epistaxis and sticky skin [1,2]. Rectal bleeding are not commonly documented side effects in dermatological practice. Previously, Erpolat et al. reported a case who developed anal fissures, rectal bleeding soon after receiving systemic retinoid therapy [3]. But detection of occult malignancy after the use of acitretin has never been documented. Interestingly, our patient had a malignancy but he was not aware of this condition. Because the tumor was very small and did not caused any symptoms, we think that the rectal bleeding was caused by the acitretin as it related to the dryness of the rectal mucosa. Rectal bleeding can be occured as a result of trauma, such as forceful defecation in xerotic, fissured rectal mucosa. As a result, the use of the acitretin in our patient caused the rectal bleeding and provided early diagnosis of the colon carcinoma. It can be said that clinicians should be aware of the possible mucocutaneous side effects of acitretin. These side effects sometimes may provide detection of occult malignancy.

TGF-Beta Suppresses VEGFA-Mediated Angiogenesis in Colon Cancer Metastasis

The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered FET cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These cells readily formed xenograft tumors in athymic nude mice. Importantly, FETα cells retained their response to TGF-beta-mediated growth inhibition, and, like the parental FET cells, expression of a dominant negative TGF-beta type II receptor (DNRII) in FETα cells (FETα/DNRII) abrogated responsiveness to TGF-beta-induced growth inhibition and apoptosis under stress conditions in vitro and increased metastatic potential in an orthotopic model in vivo, which indicates metastasis suppressor activity of TGF-beta signaling in this model. Cancer angiogenesis is widely regarded as a key attribute for tumor formation and progression. Here we show that TGF-beta signaling inhibits expression of vascular endothelial growth factor A (VEGFA) and that loss of autocrine TGF-beta in FETα/DNRII cells resulted in increased expression of VEGFA. Regulation of VEGFA expression by TGF-beta is not at the transcriptional level but at the post-transcriptional level. Our results indicate that TGF-beta decreases VEGFA protein stability through ubiquitination and degradation in a PKA- and Smad3-dependent and Smad2-independent pathway. Immunohistochemical (IHC) analyses of orthotopic tumors showed significantly reduced TGF-beta signaling, increased CD31 and VEGFA staining in tumors of FETα/DNRII cells as compared to those of vector control cells. These results indicate that inhibition of TGF-beta signaling increases VEGFA expression and angiogenesis, which could potentially contribute to enhanced metastasis of those cells in vivo. IHC studies performed on human colon adenocarcinoma specimens showed that TGF-beta signaling is inversely correlated with VEGFA expression, indicating that TGF-beta-mediated suppression of VEGFA expression exists in colon cancer patients.

A study of Fuji Intelligent Chromo Endoscopy in the diagnosis of colonrectal neoplasia

Objective To investgate the value of Fuji Intelligent Chromo Endoscopy(FICE)for the diagnosis of colonrectal polympus.Methods 197 patients who had colon polypoid lesion examined with ordinary colonoscopy from March 2009 to January 2010 were enrolled in this study.The patients were examined with magnifying conventional colonoscopy,magnifying FICE technique and magnifying chromoendoscopy technique,the pit pattern and blood capillary form.The endoscopic diagnosis was made,and compared with pathologic diagnosis.Results 359 neoplasms were detected in the197 patients,among those 91.2% were detected with magnifying conventional endoscopy,97.8% were detected with FICE technique ,there was significant difference between the two methods.the structure and form of mucosal blood capillary saw mere clearly in FICE than that in chromoendoscopy technique,(P ＜ 0.01),there was no significant difference between the two methods for showing the pit pattern.The coincident rate of FICE for the diagnosis of tumor and non-tumor polynpus was 90.3%,which was significant higher than that of chromoendoscopy 82.5% (P ＜ 0.01).Conclusion Magnifying FICE endoscopy could show mucosal microstructure and blood capillary form.It hav the superiority of high coincident rate in distinguishing neoplastic from non-neoplastic colorectal polympus compared with conventional magnifying colonoscopy and magnifying chromoendoscopy.The detected rate of early carcinoma of colon is dramatically increased with FICE.FICE could be easily operated,and hare satisfactory clinical practical value. Key words: Fuji Intelligent Chromo Endoscopy; Colon polympus; Diagnosis

Evaluation of endoscopy-assisted laparoscopic surgery in the treatment of early colon cancer

To evaluate the endoscopy-assisted laparoscopic surgery in the treatment of early colon carcinoma. The data of 55 early colon cancer patients, including 30 male, 25 female with mean age of 54 years(ranged 42 to 68), undergone endoscopy-assisted laparoscopic surgery at the colon were reviewed retrospectively. From March 2002 to December 2007, 55 early colon cancer patients were treated with endoscopy-assisted laparoscopic surgery in our institute. In 53 cases, a laparoscopic and endoscopic cooperative bowel segment resection was performed at first. Of these 53 patients, 11 cases then received laparoscopic and endoscopic cooperative radical anatomical resection according to the result of frozen section. Two cases were transferred to open surgery because of small intestinal inflation after endoscopic location. The mean operative time of cooperation was 90 min (55-240 min), and the mean blood loss was 50 ml(10-200 ml). In 51 cases(92.7%), the time for flatus passage was 2 to 3 days. The mean postoperative hospital stay was 5 d(2-15 d). No postoperative complications were found. Follow-up data were obtained by clinical examination and personal communication via telephone. The median follow-up was 42 months(ranged 3-72). Most of the patients were alive except one case died of myocardial infarction during the follow-up period. None of the patients with early colon cancer treated by the cooperative surgery had relapse or metastasis. Two cases of T1N1Mx underwent adjuvant chemotherapy. Endoscopy-assisted laparoscopic surgery offers a minimal-invasive and safe therapeutic approach for early colon cancer. The early colon cancer may be a good indication for endoscopy-assisted laparoscopic surgery when the endoscopic mucosal resection is inadequate.

487 Gene Expression Profiles for Prognosis Provide a Novel Approach for Selection of Individualized Therapies in Early Stage Colon Carcinoma

487 Gene Expression Profiles for Prognosis Provide a Novel Approach for Selection of Individualized Therapies in Early Stage Colon Carcinoma

Occurrence and Biological Properties of Sphingolipids - A Review

Sphingolipids are a complex group of polar lipids. Variations in their components (backbone, polar head group and fatty acid) engenders a large and complex structural variety which affects the biological properties of the individual molecules. Sphingolipids are omnipresent in foodstuffs, can cross the intestinal barrier and are biologically active. The quantities in food range from a few μg/kg in fruits and some vegetables up to 1 g/kg in milk products, eggs, meat and soybeans. Several positive impacts of sphingolipids on human health have been described: In vitro experiments measuring the antibacterial properties of sphingolipids have been successfully carried out. A sphingolipid-enriched diet showed inhibitory effects on the formation of early colon carcinoma precursors (Aberrant Crypt Foci (ACF)) in mice. Sphingolipid metabolites also induce apoptosis in transformed human cell cultures. Taken together, there is a high probability that sphingolipids have anticancerogenic properties in humans. Finally, a specific group of sphingolipids is essential for the maintenance of nerve function and structure and the enrichment of sphingomyelin in a cholesterol-rich diet successfully reduces cholesterol absorption. Although sphingolipids are probably not essential dietary components, they can significantly contribute to human health. Keywords: Sphingolipids, sphingomyelin, human nutrition, biological activity, cholesterol, cancer

Activation of the TGFalpha autocrine loop is downstream of IGF-I receptor activation during mitogenesis in growth factor dependent human colon carcinoma cells.

The inappropriate expression of TGFalpha in growth arrest contributes to malignant progression in human colon carcinoma cells. Early stage, non-progressed colon tumor cells show a down-regulation of TGFalpha in growth arrest and require both nutrients and growth factors for re-entry into the cell cycle. In contrast, highly progressed cells up-regulate TGFalpha during growth arrest and require only nutrients for re-entry. Given the importance of TGFalpha in malignant progression, this work addressed the regulation of TGFalpha expression in the early stage colon carcinoma cell line, FET. Growth-arrested FET cells down-regulated the expression of TGFalpha, EGFr and, in turn, EGFr activation. These quiescent cells continued to express high levels of IGF-IR protein, but IGF-IR activation was undetectable. Cell cycle re-entry required exogenous growth factor activation of the IGF-IR by insulin or IGF-I. This IGF-IR activation resulted in S phase re-entry and was accompanied by an approximate threefold induction of TGFalpha expression along with EGFr activation at 1 h following release from growth arrest. Activation of IGF-IR occurred within 5 min of cell-cycle re-entry. Previously identified DNA binding proteins which bind to a unique TGFalpha/EGF response element within the TGFalpha promoter were similarly induced following IGF-IR activation. The addition of EGFr neutralizing antibodies abolished the activated IGF-IR stimulated S phase re-entry. Moreover, disruption of the growth arrest associated down-regulation of TGFalpha in FET cells by constitutive TGFalpha expression abrogated the requirement for IGF-IR activation for cell cycle re-entry. Consequently, this study indicates, for the first time, that IGF-IR activation up-regulates components of the TGFalpha autocrine loop resulting in TGFalpha-mediated EGFr activation which was critical for IGF-IR mediated re-entry into the cell cycle from the growth-arrested state.

Early sigmoid colon carcinoma developed from a pedunculated polyp

A 60‐year‐old man underwent routine colonoscopy, and was noted to have a pedunculated polyp in the sigmoid colon. The pathologic diagnosis was adenoma, and due to patient’s personal circumstances, the lesion was left untreated. The colonoscopic examination was repeated 4 years and 11 months later, to find that the polyp had transformed into an elevated lesion with irregularly depressed surface. The patient was diagnosed as having early sigmoid cancer, and underwent sigmoidectomy. The histologic examination of the excised specimen revealed well‐differentiated adenocarcinoma with invasion into the submucosal layer. Through studying the natural course of colon cancer, it has become known that the advanced cancers commonly develop from polyps with short pedicles (sessile polyps). This case represents an early sigmoid cancer developed from a pedunculated polyp, which differs from the current mainstream concept of ‘polyp‐cancer sequence of colon cancer.’

RESECTED SOLITARY SPLENIC METASTASIS 2 YEARS AFTER EARLY COLONIC CARCINOMA IN ONE ADULT

We report a resected case of solitary splenic metastasis after polypectomy of early sigmoid colon cancer two years before. The patient was an 82-year-old woman. She had under gone an endoscopic polypectomy for a sigmoid lp typed polypoid lesion at another hospital in October 1994. Histologically, Diagnosis was moderately differentiated adenocarcinoma invading the submnucosa (sm 2, ly 1, v 1, ce [-]). An additional resection was recommended, but she refused and had been followed-up carefilly. She was seen at our hospital because of urological symptoms in October 1996. An abdominal ultrasonography and a computed tomography showed a 3cm tumor of the spleen. The serum lactase dehydrogenase (LDH) level was slightly elevated, Ga scintigraphy revealed a slight accumulation in the spleen and no abnormality in any other organ. A preoperative diagnosis of primary tumor of the spleen was made and laparoscopic splenectomy was performed. Histopathological findings of the resected splenic tumor detected the same histological type as the early sigmoid polypoid carcinpma. Therefore, a diognosis was determined of metastasis of the early sigmoid colon carcinoma to the spleen without any other distant metastases. This case was unique in that the tumor of early stage colon cancer resulted in splenic metastasis in two years.

日本住血吸虫卵が介在した異時性多発早期大腸癌の１例

日本住血吸虫卵が介在した異時性多発早期大腸癌の１例

C-Ha-ras not c-Ki-ras activation in three colon tumour cell lines.

Using the NIH 3T3 transformation assay system, an activated c-Ha-ras transforming gene has been identified in three distinct early passage colon carcinoma cell lines isolated from an invasive, differentiated, adenocarcinoma. The p21 c-Ha-ras gene product from these cell lines displayed an altered electrophorectic mobility and a point mutation in the DNA coding sequence leading to an amino acid substitution at position 12.