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Biomedical subjects

Masaru Yokoyama

Publications and source records attributed to Masaru Yokoyama.

At least 19 recordsLinked to original sources

Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus.

To understand the pathogenesis and develop an animal model of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), the Frankfurt 1 SARS-CoV isolate was passaged serially in young F344 rats. Young rats were susceptible to SARS-CoV but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. After 10 serial passages, replication and virulence of SARS-CoV were increased in the respiratory tract of young rats without clinical signs. By contrast, adult rats infected with the passaged virus showed respiratory symptoms and severe pathological lesions in the lung. Levels of inflammatory cytokines in sera and lung tissues were significantly higher in adult F344 rats than in young rats. During in vivo passage of SARS-CoV, a single amino acid substitution was introduced within the binding domain of the viral spike protein recognizing angiotensin-converting enzyme 2 (ACE2), which is known as a SARS-CoV receptor. The rat-passaged virus more efficiently infected CHO cells expressing rat ACE2 than did the original isolate. These results strongly indicate that host and virus factors such as advanced age and virus adaptation are critical for the development of SARS in rats.

Age Factors↗

Primitive neuroectodermal tumor arising in the colon: report of a case.

Peripheral primitive neuroectodermal tumors (pPNETs) are usually found in the soft tissue of the extremities, paravertebral region, and chest wall. We report a rare case of a pPNET arising in the colon. A 59-year-old man underwent left hemicolectomy for an infiltrative ulcerating tumor, 11 cm long, in the descending colon. Histological examination of the resected specimen revealed small, round cell proliferation with rosette-like structures, and confirmed regional lymph node involvement and peritoneal dissemination near the primary tumor. Immunohistochemically, the tumor cells were positive for synaptophysin and MIC2 (CD 99). ESW-FLI1 chimeric mRNA was detected in the tumor by reverse transcriptase-polymerase chain reaction. The patient underwent resection of recurrence in the retroperitoneum 3 months later, but metastasis rapidly developed and he died of the disease 7 months after his first operation.

Base Sequence↗

[Hepatic lymph node involvement in patients with synchronous multiple liver metastases of colorectal cancer].

BACKGROUND AND PURPOSE: Hepatic arterial infusion chemotherapy for unresectable liver metastases of colorectal cancer is generally indicated to patients without extra hepatic lesions. This study was performed to examine the status of hepatic lymph node metastasis as an extra hepatic lesion in patients with synchronous multiple liver metastases of colorectal cancer. PATIENTS AND METHODS: A total of 111 hepatic lymph nodes were removed from 33 patients with synchronous liver metastases of colorectal cancer during resection of the primary tumor at the D2- or D3- level. The frequency of hepatic lymph node metastases and factors predictive for hepatic lymph node metastasis were examined. RESULTS: Hepatic lymph node metastasis was detected in nine patients (27%): The sites were classified into three categories: (1) along the hepatic arteries in three, (2) in the hepato-duodenal ligament except the peri-hepatic arterial region in three, and (3) both in three. The serum level of CEA (p = 0.02), CA19-9 (p = 0.05), and the rate of lymph node metastasis of the primary lesion (p = 0.08) were higher or tended to be higher in patients with hepatic lymph node metastases than in those without. There was no significant relationship between the involvement of hepatic lymph nodes and the other clinicopathologic factors examined. CONCLUSION: We should note the frequency of hepatic lymph node metastasis in the treatment of unresectable liver metastases of colorectal cancer.

Carcinoembryonic Antigen↗

[The relationship between plasma level of VEGF or soluble Flt-1 and efficacy of hepatic arterial chemotherapy in patients with liver metastasis of colorectal cancer].

PURPOSE: To clarify the clinical significance of determining plasma levels of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in colorectal cancer, changes in plasma levels of VEGF and sFIt 1 during hepatic arterial chemotherapy were investigated in patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: The relationship between plasma level of VEGF or sFlt-1 and serum level of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), or the efficacy of hepatic arterial chemotherapy was investigated in patients with liver metastases of colorectal cancer (n=19). Plasma levels of VEGF and sFlt-1 were determined by the enzyme linked immunosorbent assay. RESULTS: There was a positive relationship between plasma level of sFlt-1 and serum level of CEA (p = 0.13). The other combinations did not show any statistical correlations. Also, in terms of the doubling time (DT), there was a positive relationship between the sFlt1-DT and the CEA-DT (p = 0.04). The levels of VEGF tended to change in accordance with the efficacy of chemotherapy. In contrast, plasma levels of sFlt-1 increased in patients with the progressive disease, whereas the levels did not decrease in patients with the partial response. CONCLUSIONS: These results suggested that (1) VEGF may be a useful tumor marker during the chemotherapy in patients, whose CEA and CA19-9 are below the cutoff, and (2) the shrinkage of liver metastases may not cause a decrease in sFlt-1 or the half-life of sFlt-1 may be considerably long.

Antineoplastic Combined Chemotherapy Protocols↗

HIV-1 proteases from drug-naive West African patients are differentially less susceptible to protease inhibitors.

BACKGROUND: Now that highly active antiretroviral therapy (HAART) is being initiated on a large scale in West Africa, it remains controversial whether protease inhibitors (PIs), originally designed and tested against human immunodeficiency virus type 1 (HIV-1) subtype B, are equally effective against the non-B subtypes that are prevalent in West African countries. In this study, we investigated whether Ghanaian HIV-1 isolates, as representatives of West African isolates, are susceptible to PIs. METHODS: We first generated an HIV-1 protease cassette vector proviral DNA carrying a luciferase gene, which allows patient-derived HIV-1 proteases to be inserted and to be subjected to both genotypic and phenotypic assays. HIV-1 protease genes derived from 39 treatment-naive Ghanaian patients were used in this experiment as representatives of West African strains. The cloned patient-derived HIV-1 protease genes were first sequenced and then genetically compared. Phenotypic analysis was performed with Ghanaian HIV-1 protease-chimeric viruses in the presence of 6 different PIs. Structural models of HIV-1 protease homodimers were constructed by the molecular modeling software. RESULTS: Genetic analysis of cloned patient-derived HIV-1 protease genes indicated that most of the Ghanaian HIV-1 proteases are placed as subtype CRF02_AG strains, which are phylogenetically distant from subtype B strains, and that Ghanaian HIV-1 proteases do not harbor known major mutations influencing drug resistance but commonly carry 2-3 minor mutations. Phenotypic analysis performed with HIV-1 protease-recombinant viruses in the presence of 6 different PIs revealed that Ghanaian HIV-1 proteases are differentially less susceptible to the PIs. In support of this finding of differential susceptibility, structural analysis showed a significant distortion of nelfinavir, but not of amprenavir, in the Ghanaian protease pocket, suggesting nelfinavir might be less insertable into the Ghanaian protease than into the protease of subtype B. CONCLUSIONS: These findings provide implications for the combination of PIs during the introduction of HAART into West Africa.

Adult↗

Incarcerated recurrent rectal prolapse with ileal strangulation: report of a case.

We report a rare case of incarcerated rectal prolapse with ileal strangulation occurring after a Gant-Miwa procedure with anal encircling (Thiersch's procedure) for recurrent rectal prolapse. The patient was a 78-year-old woman who presented to our outpatient clinic the day after sudden rectal protrusion had occurred. She had undergone a Gant-Miwa procedure for rectal prolapse 4 years previously, and another Gant-Miwa procedure with anal encircling for recurrent rectal prolapse 18 months earlier. The patient attempted to reduce the prolapse manually, but was unsuccessful. On admission, a 10 x 4-cm semispherical mass was observed extra-anally, with a necrotic surface. We performed an emergency laparotomy, which rerealed a prolapse of the anterior wall of the rectum with part of the ileum protruding into the sac formation. Thus, we resected the incarcerated ileum followed by primary anastomosis and proctectomy (Hartmann's procedure) with good results. This case demonstrates that ileal strangulation can occur as a complication of rectal prolapse recurrence after perineal repair.

Aged↗

Amino acid 36 in the human immunodeficiency virus type 1 gp41 ectodomain controls fusogenic activity: implications for the molecular mechanism of viral escape from a fusion inhibitor.

We have previously described a human immunodeficiency virus type 1 (HIV-1) proviral clone, pL2, derived from defective viral particles with higher fusogenicity than the prototypic NL4-3 virus. In this study, we attempted to determine the region that confers the enhanced fusion activity by creating envelope recombinants between pL2 and pNL4-3, as well as point mutants based on pNL4-3. The results indicate that amino acid 36 of gp41 is key for the fusogenic activity and infectivity enhancement and that glycine 36 (36G) of gp41 in pL2 is conserved in nearly all HIV-1 isolates except for pNL4-3. The mutation 36G-->D in a primary-isolate-derived Env decreased syncytium-forming activity and infectivity. The assays for cell-cell fusion and viral binding suggested that the enhanced fusion mediated by the 36D-->G mutation is not due to increased binding efficiency but is directly due to actual enhancement of viral fusion activity. Interestingly, this amino acid position is exactly equivalent to that at which the mutation of HIV-1 isolates that have escaped from a fusion inhibitor, enfuvirtide (T-20), has been frequently observed. The correlation between these previous findings and our findings was suggested by structural analysis. Our finding, therefore, has implications for a molecular basis of the viral escape from this drug.

Amino Acids↗

Human immunodeficiency virus mutagenesis during antiviral therapy: impact of drug-resistant reverse transcriptase and nucleoside and nonnucleoside reverse transcriptase inhibitors on human immunodeficiency virus type 1 mutation frequencies.

The development of antiviral drug resistance is an important problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Potent antiretroviral therapy is currently used for treatment, and typically consists of at least two reverse transcriptase (RT) inhibitors. We have previously reported that both drugs and drug-resistant RT mutants can increase virus mutation frequencies. To further assess the contributions of nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), and drug-resistant RTs to HIV mutagenesis, a new high-throughput assay system was developed. This assay system was designed to specifically detect frameshift mutations in the luciferase gene in a single virus replication cycle. New drug-resistant RTs were identified that significantly altered virus mutation frequencies. Consistent with our previous observations of NRTIs, abacavir, stavudine, and zalcitabine increased HIV-1 mutation frequencies, supporting the general hypothesis that the NRTIs currently used in antiviral drug therapy increase virus mutation frequencies. Interestingly, similar observations were made with NNRTIs. This is the first report to show that NNRTIs can influence virus mutation frequencies. NNRTI combinations, NRTI-NNRTI combinations, and combinations of drug and drug-resistant RTs led to significant changes in the virus mutation frequencies compared to virus replication of drug-resistant virus in the absence of drug or wild-type virus in the presence of drug. This indicates that combinations of RT drugs or drugs and drug-resistant virus created during the evolution of drug resistance can act together to increase HIV-1 mutation frequencies, which would have important implications for drug therapy regimens. Finally, the influence of drug-resistant RT mutants from CRF01_AE viruses on HIV-1 mutation frequencies was analyzed and it was found that only a highly drug resistant RT led to altered virus mutation frequencies. The results further suggest that high-level drug-resistant RT can significantly influence virus mutation frequencies. A structural model that explains the mutation frequency data is discussed.

Anti-HIV Agents↗

[RNA viruses and mutations].

Actively replicating RNA viruses in nature are continually changing their genetic information by spontaneous mutations. These changes often result in alterations in immune-sensitivity, drug-sensitivity, cell-tropism, and host-range, causing uncontrollability of the pathogen and emerging/re-emerging infections. To better understand the virus changes and develop effective methods to control the moving targets, it is essential to obtain information on changes in viral genomes and proteins. Although information on genetic changes is being accumulated very rapidly, assessment of changes in protein structure and function still requires time-consuming works. In this review, we will overview mutation studies of human immunodeficiency virus and other RNA viruses. In addition, we will introduce recent advances in the computational science and its application on mutation studies and drug development.

Animals↗

[Clinical significant of semiquantificating DNA topoisomerase- I mRNA in colorectal cancer].

PURPOSE: To examine the clinical significance of determining the expression levels of DNA topoisomerase- I (topo-I) mRNA of colorectal cancer. METHODS: The relative expression levels of topo-I mRNA in primary colorectal cancer and adjacent normal mucosa were semiquantificated by the RT-PCR method. The relative expression of thymidylate synthase (TS) mRNA of the primary lesions was also examined. RESULTS: The topo- I mRNA expression was higher in the tumorous tissue than in the normal mucosa (n=22, p<0.01). The topo- I mRNA expression did not significantly correlate with 9 clinicopathological variables examined (n=22). In patients who received irinotecan hydrochloride (CPT-11) following the failure of 5-fluorouracil-based treatment, the topoI mRNA expression did not differ nor correlate with the response to CPT-11 (PR, n=14; SD, n=11; PR; n=24) (p=0.91). In these patients, there was no relationship between the topo I mRNA expression and the TS mRNA expression (p=0.22, r=0.18). In addition, the efficacy of CPT-11 did not correlate with combinations subdivided according to the expression levels of topo- I mRNA and TS mRNA. CONCLUSIONS: Determination of topo- I mRNA levels of primary colorectal cancer may not be useful for predicting the efficacy of CPT-11 treatment alone or in combination with TS mRNA levels.

Aged↗

[Expression of mRNA levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and orotate phosphoribosyltransferase of colorectal cancer--relationships among mRNA levels in association with response to 5-FU based treatment].

We semiquantificated the mRNA levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase(OPRT) from the frozen tissue of colorectal cancer, in order to examine the relationships among these enzymes and the efficacy for 5-fluorouracil (FU)-based treatment in terms of the combinations of the expression levels of these enzymes. There were weak and positive relationships among TS mRNA expression and OPRT mRNA expression or DPD mRNA expression, while there was no significant relationship between DPD mRNA expression and OPRT mRNA expression (n = 112). In 39 patients who received 5-FU-based chemotherapy with evaluable lesions, patients with low TS expression (n = 23) showed a higher response rate (52%) as compared to those with high TS expression (13%, p = 0.02). Patients with low TS, low DPD, or high DPD expression tended to show a higher response rate (50%) than those with the other combinations (26%, p = 0.09). In addition, all of the responders with only one favorable factor (n = 4) were associated with low TS or low DPD expression. In conclusion, low TS expression followed by low DPD expression is important to predict the efficacy of 5-FU-based treatment for colorectal cancer. However, it may be of little significance to semiquantify the expression of OPRT.

Adult↗

[Tumoral dihydropyrimidine dehydrogenase expression and efficacy of 5-fluorouracil plus leucovorin plus UFT therapy in patients with colorectal cancer].

The purpose of this study was to examine the relation between tumoral expression of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme of the degradation pathway 5-fluorouracil (5-FU), and the efficacy of 5-FU based chemotherapy for colorectal cancer. Twenty-eight colorectal cancer patients who had underwent noncurative resection (n = 16) or had developed recurrence (n = 12) were enrolled. All patients were given 5-FU plus leucovorin intravenously and UFT (1 M Tegafur, 4 M Uracil) perorally. The expression levels of the DPD in the primary lesions were determined by the enzyme-linked immunosorbent assay. Group A (n = 10) consisted of one patient with complete response, 4 with partial response, and 5 with no change (time to disease progression (TTP) > = 90 days). Group B (n = 18) consisted of 14 patients with progressive disease and 4 with NC (time to progression, < 90 days). The tumoral DPD levels did not differ between the groups (p = 0.58). There were no effective cases (n = 6) whose tumoral DPD levels were equal to or more than 83.2 U/mg protein (high DPD expression). There were marked overlaps in the DPD levels between the two groups whose DPD levels were less than 83.0 U/mg protein (moderate or low expression). These results suggest that high expression of tumoral DPD would be predictive to failure of fluoropyrimidine-based treatment. However, it is unlikely to set the optimal cutoff value for predicting the efficacy of this type of chemotherapy.

Adult↗

[Usefulness of F-18-fluorodeoxyglucose positron emission tomography for evaluating the efficacy of transient hepatic arterial chemoembolization for liver metastases of rectal cancer--a case report].

It is pointed out that there can be a discrepancy between the effect diagnosed by radiographic imaging and that by histological examination, when we treat patients with liver metastases of colorectal cancer by a transient hepatic arterial chemoembolization. We report a case of liver metastases of rectal cancer in which F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for evaluating the therapeutic efficacy for transient hepatic arterial chemoembolization. A 58-year-old man with synchronous liver metastases (H2) of rectal cancer underwent a low anterior resection, a partial hepatectomy, cholecystectomy, and ligation of the gastroduodenal artery. After these operations, the patient received 6 hepatic arterial injections with degradable starch microspheres (300-600 mg), adriamycin (30 mg), and mitomycin C (10 mg) for the remaining metastatic lesion (S7). Although abdominal CT scan revealed a partial response, FDG-PET did not show any abnormal deposits. Hepatic posterior segmentectomy was performed 7 months after the first operation. Histological examination did not show any viable tumor cells in the resected specimen.

Chemoembolization, Therapeutic↗

[Histological examination of the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C for liver metastases of colorectal cancer--second report].

We histologically examined the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C (DSM therapy) for liver metastases of colorectal cancer. The subjects were 15 liver metastatic lesions from 9 patients with colorectal cancer who underwent potentially curative hepatectomy after DSM therapy. Ages were ranged from 36 to 71 years old (mean, 57). The ratio of male to female was 4 to 5. Six patients had synchronous lesion(s). A single injection dosage of the DSM therapy was comprised of 300-600 mg degradable starch microspheres, 30 mg ADM, and 10 mg MMC. Three lesions from the two patients who were given a single DSM therapy did not show any radiographical changes. In addition, histological examination of these lesions demonstrated a grade 1 effect. The radiographical effect of the 12 lesions from the 7 patients, who were given the DSM therapy at least three times, showed SD in 4 lesions, PR in 6 lesions, and PD in two lesions. Histological examination of these lesions demonstrated Grade 2 in 4 lesions and Grade 3 in 5 lesions. In conclusion, it was histologically confirmed that a repeated DSM therapy could cause satisfactory effects beyond expectations by radiographic imaging in patients with liver metastases of colorectal cancer.

Adult↗

[Efficacy of hepatic arterial infusion of adriamycin and mitomycin C mixed with degradable starch microspheres for liver metastasis of colorectal cancer--correlation with the mRNA expression of DNA topoisomerase-IIalpha and glutathione-S transferase-pi in primary lesions].

DNA topoisomerase-IIalpha (topo-IIalpha) is a target enzyme of adriamycin (ADM). Glutathione-S-transferase-pi is known to be correlated with the resistance of various anticancer drugs including mitomycin C (MMC) and ADM. Expression levels of topo-IIalpha and GST-pi mRNA of primary colorectal lesions were semi-quantitatively determined by the RT-PCR method in 22 patients with colorectal cancer, who underwent hepatic arterial infusion of ADM and MMC mixed with degradable starch microspheres for synchronous (n=17) or metachronous (n=5) liver metastasis. Expression of topo-IIalpha mRNA/beta-actin mRNA was 0.872+/-0.564 (mean+/-SD) in responders (PR, n=10) and 0.369+/-0.133 in non-responders (SD+PD, n=12) (p=0.047). The relative expression of GST-pi was 0.638+/-0.593 in responders and 1.014+/-0.682 in non-responders (p=0.22). These results suggest that determining the mRNA expression of topo-IIalpha is useful for predicting the efficacy for this regimen, whereas determining the mRNA expression of GST-pi is not.

Adult↗

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS: Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS: Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.

Adenocarcinoma↗

[Results of prophylactic hepatic arterial chemotherapy for liver metastases of Dukes C colorectal cancer--correlation with tumoral expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53, or orotate phosphoribosyl transferase].

The purpose of this study was (1) to disclose data from a non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from Dukes'C colorectal cancer, (2) to examine the influence of the expression of dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), and p53 in the primary lesion on this chemotherapy, and (3) to examine the expression of orotate phosphoribosyl transferase (OPRT) mRNA levels in the cases of recurrence included in this study. Patients who underwent curative resection of Dukes'C colorectal cancer between November 1996 and April 2000 were examined. After curative resection, patients were non-randomly divided into two groups after obtaining their informed consent: Hepatic arterial infusion (HAI) group patients (n = 28) were given 5-FU (500 mg/body for 1 h per week, repeated 50 times) via the hepatic artery and peroral UFT-E after resection of Dukes'C colorectal cancer. Control group patients (n = 21) received UFT-E alone. Liver metastasis-free survival did not differ between the groups. Immunohistochemical examinations revealed that the expression of tumoral DPD or p53 was unlikely to affect the hepatic recurrence, although patients with a low expression of TS tended to have better survival in both groups. However, multivariate analysis by the Cox proportional hazard model revealed that a significant prognostic factor influencing the hepatic recurrence is extensive venous invasion. Expression levels of OPRT mRNA, measured in tumors of patients with recurrence (n = 6 for the HAI group; and n = 4 for the control group) were not significantly different between the groups. These results suggest that (1) intermittent hepatic arterial infusion of 5-FU in addition to oral UFT-E was not more useful than administration of UFT alone, and (2) the expression of DPD, TS, p53, and OPRT in the primary lesion was unlikely to affect the prognosis of patients included in this study.

Adult↗

[Relationship between effectiveness of hepatic artery injection chemotherapy and serum VEGF].

Elevated plasma VEGF levels were reported in patients with colorectal cancer. This report presents regarding VEGF in patients who underwent hepatic artery injection chemotherapy (TAI) for liver metastasis of colorectal cancers. Thirty patients who underwent TAI for liver metastases of colorectal cancer during January 2002 to March 2003 were studied. Their serum CEA, CA19-9, and plasma VEGF were measured, and the relationships between these, their doubling times (DT) and therapeutic efficacy were examined. While the detected values and DTs were not considered significant, the tendency for DT to be the same was observed. One case with negative CEA and CA19-9 had high VEGF but negative VEGF-DT, which is compatible with therapeutic effects (PR). It appears that VEGF is a parameter that changes without direct correlation to CEA or CA19-9, and that VEGF may possibly be used as a therapeutic marker for cases with negative CEA or CA19-9.

Antineoplastic Combined Chemotherapy Protocols↗