Kazuhiko Hoshi

Milk Consumption Is a Risk Factor for Prostate Cancer: Meta-Analysis of Case-Control Studies

Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further.

Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum.

Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.

Estrogen: one of the risk factors in milk for prostate cancer.

Studies to elucidate the cause of prostate cancer have met with little success to date. Epidemiological studies suggested that milk consumption is probably as one of the risk factors for prostate cancer. The studies thus focused on the fat and calcium in milk, but reached no definitive conclusion. According to the measurements of estrogen levels in milk by different studies, it was suggested that estrogen in milk was a possible risk to cause prostate cancer. One reason supporting this hypothesis is that Western diet (characterized by milk/dairy products and meat) causes a trend of increasing levels of estrogens, and Western males show a higher incidence rate of prostate cancer than Asia males. Estrogen levels in prostate fluid are also correlated very well with the prostate cancer. During several decades, estrogens, together with testosterone, was commonly used to induce the rodent model of prostate cancer. Our hypothesis also was supported by the presence of estrogen receptors in the prostate gland and the genotoxic role of estrogens on the prostate gland, as possible mechanisms. Therefore, if modern milk consumption does expose consumers to high levels of estrogen and plays an adverse role in prostate cancer, action should be taken to produce the noncontaminant milk.

Absence of human papillomavirus infection in minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia.

The human papillomavirus (HPV) is basically always detected in squamous cell carcinoma of the cervix and its precursors; a high incidence of HPV also has been reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in 1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA) from LEGH preoperatively or postoperatively by clinical and pathologic features. The relationships between HPV and MDA or LEGH have not been studied well because of the rare incidence of the two diseases. To our knowledge, the HPV status in LEGH has not been reported. This study was designed to investigate HPV infection in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor tissue lesions were microdissected and the detection of HPV and its typing were analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of squamous cell carcinoma and three of five cases of adenocarcinoma. However, no HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA. These results suggest that MDA and LEGH are probably not related to HPV infection.

Chromatoid bodies: aggresome-like characteristics and degradation sites for organelles of spermiogenic cells.

We investigated the localization of several markers for lysosomes and aggresomes in the chromatoid bodies (CBs) by immunoelectron microscopy. We found so-called aggresomal markers such as Hsp70 and ubiquitin in the core of the CBs and vimentin and proteasome subunit around the CBs. Ubiquitin-conjugating enzyme (E2) was also found in the CBs. In tubulovesicular structures surrounding the CBs, lysosomal markers were detected but an endoplasmic reticulum retention signal (KDEL) was not. Moreover, proteins located in each subcellular compartment, including the cytosol, mitochondria, and nucleus, were detected in the CBs. Signals for cytochrome oxidase I (COXI) coded on mitochondrial DNA were also found in the CBs. Quantitative analysis of labeling density showed that all proteins examined were concentrated in the CBs to some extent. These results show that the CBs have some aggresomal features, suggesting that they are not a synthetic site as proposed previously but a degradation site where unnecessary DNA, RNA, and proteins are digested.

The prognosis of fetuses with transient nuchal translucency in the first and early second trimester

Objective. The purpose of this study was to evaluate the prognosis of fetuses with transient nuchal translucency before 15 weeks of gestation.

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia : A report of four cases with histochemical and immunohistochemical analyses

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.

Estimation of prognoses for cervical intraepithelial neoplasia 2 by p16INK4a immunoexpression and high-risk HPV in situ hybridization signal types

The present study used immunohistochemical staining and in situ hybridization (ISH) to examine whether progression of cervical intraepithelial neoplasia, grade 2 (CIN 2) can be predicted by p16INK4a immunoexpression and high-risk human papilloma virus (HPV) ISH signal types. We studied 52 cases histologically diagnosed with CIN 2: dysplasia regressed in 28 cases; 13 cases progressed to CIN 3; and CIN 2 persisted in 11 cases. Expression of p16INK4a and high-risk HPV signal both related to grade of CIN. Stronger p16INK4a immunoexpression and a higher frequency of expression of a punctate nuclear signal were observed in CIN 2 lesions before progression compared with those before regression. CIN 2 cases in which moderate to strong immunoexpression of p16INK4a and a punctate signal were observed simultaneously progressed to CIN 3 in 10 (91%) of 11 cases. CIN 2 cases with moderate to strong immunoexpression of p16INK4a and a high-risk HPV punctate signal should be treated because of the great risk of progression.

The Novel Isoform of the Progesterone Receptor cDNA in the Human Testis and Detection ofIts mRNA in the Human Uterine Endometrium

A novel isoform (termed isoform S) of the progesterone receptor (PR) cDNA (PR isoform S cDNA) which consists of a previously unidentified 5’ sequence and exons 4–8 of the intracellular PR gene has been cloned from the human testicular cDNA library. The 5′ sequence of the message was confirmed to be derived from a novel exon (termed exon S) by genomic cloning. The expression level of the PR isoform S mRNA was higher in the spermatozoon than in the uterine endometrium with a lower expression level of the PR isoforms B and A mRNAs in the spermatozoon than in the endometrium. These results implied that the PR isoform S which was possibly translated from the PR isoform S mRNA in the spermatozoon might be related to the cell surface membrane PR. Moreover, the PR isoform S in the uterine endometium might play some physiological and/or pathogenic roles.

LOW-FAT MILK PROMOTES THE DEVELOPMENT OF 7,12-DIMETHYLBENZ(A)ANTHRACENE (DMBA)-INDUCED MAMMARY TUMORS IN RATS

Commercial cow milk contains considerable amounts of estrogens. Our study assessed the effect of commercial low‐fat milk on the development of 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary tumors in rats. Eighty 6‐week‐old female Sprague‐Dawley rats received a single oral dose of 5 mg DMBA. Twenty‐four hours later, the animals were divided into 4 groups of 20 animals each and given 1 of 4 test solutions for 20 weeks as their drinking liquid: low‐fat (1%) milk (M), artificial milk (A), estrone sulfate solution (0.1 μg/ml, E), or tap water (W). The artificial milk was formulated to supply essentially the same calories as the milk. The low‐fat milk contained 378 pg/ml estrone sulfate. Tumor incidence, the cumulative number of tumors and the sum of tumor diameters were higher in the M and E groups than in the A or W groups. Overall, the development of mammary tumors was in the order: M = E > A = W. Whereas the plasma 17β‐estradiol concentration in the M group was the 2nd highest after the E group, the plasma level of insulin‐like growth factor (IGF‐I) was significantly higher in the M group than in the other 3 groups. In conclusion, commercially available low‐fat milk promotes the development of DMBA‐induced mammary tumors in rats. The degree of the promotion is almost comparable to that of 0.1 μg/ml estrone sulfate. The high estrogen content in the milk may be responsible for the promotional effects, acting in concert with other hormones such as IGF‐I.