Hideaki Komatsu

Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines

Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem‐loop‐mediated reverse transcription real‐time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR‐138, was significantly downregulated in ATC cell lines in comparison with PTC (P < 0.01). Eleven miRNA (including miR‐138) potentially targeting the human telomerase reverse transcriptase (hTERT) gene were totally downregulated in both ATC and PTC cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR‐138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = –0.392, P = 0.148). We demonstrated that overexpression of miR‐138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR‐138 and the hTERT 3′‐untranslated region by luciferase reporter assay. These results suggest that loss of miR‐138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma. (Cancer Sci 2008; 99: 280–286)

Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines.

Aim:  The cross‐talk pathway between angiotensin II (AngII) and the epidermal growth factor receptor (EGFR) mediated by epidermal growth factor (EGF)‐like ligands cleaved by a disintegrin and metalloprotease (ADAM) has been elucidated in several cell types. Even though the liver is a representative angiotensinogen‐producing organ, such cross‐talk has never been elucidated in hepatocellular carcinomas (HCCs). We investigated whether AngII exerted a mitogenic effect on HCC cell lines through the AngII–EGFR cross‐talk pathway.

Pulmonary Hilar Lymph Node Metastasis of Breast Cancer Induced Bronchopleural Fistula and Superior Vena Cava Syndrome

Patient: Female, 56 Final Diagnosis: Broncho-pleural fistula • empyema • supra-vena cava syndrome Symptoms: Dyspnea • fever • facial edema Medication: — Clinical Procedure: — Specialty: Oncology and Pulmonology Objective: Unusual clinical course Background: It is extremely rare for pulmonary hilar lymph node metastasis (PHLNM) of a cancer to be independently lethal. Here, we report an exceedingly rare case of cavitation in PHLNM from breast cancer triggering bronchopleural fistula and empyema (BPFE), complicated with superior vena cava syndrome (SVCS). Case Report: A 56-year-old woman who had undergone left segmental mastectomy and axillary lymph node dissection due to left breast cancer was then treated for 1 year with postoperative adjuvant chemotherapy. Recurrence of right PHLNM was observed 2 years after the operation, for which 3 courses of bevacizumab (BEV) and paclitaxel combination chemotherapy were administered. The woman had dyspnea and fever during the washout period, and CT examination revealed fistula formation between the right PHLNM cavitation and right main bronchus, so she was admitted for further treatment. This fistula rapidly progressed to BPFE, and contralateral aspiration was observed to cause pneumonia of the left lung. In addition, edema of both upper limbs and head and neck were observed, and CT examination revealed SVCS caused by re-enlargement of PHLNM. Active treatment was performed, but the recommencement of chemotherapy was not possible, and she died on Day 150 of admission. Conclusions: We think that PHLNM deteriorated to central necrosis due to chemotherapy with BEV taking effect, leading to formation of BPFE. The case was also made more difficult due to the complication of SVCS caused by the re-enlarged PHLNM.

Long-term complete remission of metastatic breast cancer, induced by a steroidal aromatase inhibitor after failure of a non-steroidal aromatase inhibitor.

Patient: Female, 56 Final Diagnosis: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reported incomplete cross-resistance between different aromatase inhibitors, few cases of complete responses of recurrent metastatic breast cancer occurring after substituting a second aromatase inhibitor have been reported. We here present a rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer with long-term complete remission following substitution of a steroidal aromatase inhibitor. Case Report: We present the case of a 56-year-old Japanese woman who underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0, M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and radiation therapy, and then began hormonal therapy with anastrozole. Twelve months postoperatively, computed tomography (CT) revealed multiple lung metastases. Exemestane was substituted for anastrozole. After 3 months of exemestane, CT showed that all lung metastases had completely resolved. Her complete response was maintained for 5 years: she died during a tsunami 6 years after the initial surgery. Conclusions: Substitution of a steroidal for a non-steroidal aromatase inhibitor produced a sustained complete remission in a patient with hormonal receptor-positive postmenopausal recurrent breast cancer. Achieving complete response after switching from a non-steroidal to a steroidal aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent breast cancer contributed to a higher quality of life for the patient. Further investigation is needed to identify the predictors of long-term remission following such a switch.

A Phase I Study of Capecitabine Combined with CPT-11 in Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m2) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m2/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m2, as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m2. The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment.

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Sporadic breast metastasis derived from renal cell carcinoma: A case report

Breast metastases from extramammary tumors are much less common than primary breast tumors and are usually due to melanoma, lymphoma, or leukemia. Metastases to the breast from renal cell carcinoma (RCC) are very rare. Here we report on a case of solitary breast metastasis from RCC, which occurred 2 years after nephrectomy.

The efficacy of sodium azulene sulfonate L-glutamine for managing chemotherapy-induced oral mucositis in cancer patients: a prospective comparative study

BackgroundThe efficacy of sodium azulene sulfonate L-glutamine (GA) in treating oral mucositis caused by the administration of anticancer agents has not been previously elucidated. Therefore, this prospective comparative study was conducted to evaluate the efficacy of GA in treating oral mucositis caused by chemotherapy regimens involving fluorinated pyrimidine anticancer drugs.MethodsThe subjects of this study were patients with oral mucositis of grade 2 or higher while on outpatient chemotherapy regimens involving fluorinated pyrimidine anticancer drugs for colorectal or breast cancer. The subjects were randomly divided into a group that received GA (the GA group) or a group that did not receive GA (the control group) by using the closed-envelope method. GA was administered three times a day every day from the first day of the regimen until the final day. The primary endpoint was the development of oral mucositis of grade 2 or higher. The secondary endpoint was the severity of oral pain, which was judged using an 11-stage numerical rating scale (NRS) ranging from 0 to 10.ResultsThe proportion of patients with oral mucositis of grade 2 or higher was 32.4% in the GA group and 57.6% in the control group. The GA group had a significantly lower frequency of occurrence. The changes in the NRS scores before and after the trial began were − 2.9 ± 0.6 in the GA group and − 1.2 ± 0.5 in the control group. The NRS score decreased more significantly in the GA group than in the control group (P = 0.046). One patient stopped GA treatment voluntarily due to nausea; other than nausea, no GA-related side effects were observed.ConclusionsGA protects against oral mucositis and reduces the severity of prevailing oral mucositis symptoms. Our findings indicate that GA is a highly safe and convenient drug.

Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy

OBJECTIVE Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. METHODS Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. RESULTS As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness. CONCLUSIONS This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant.